Virus World

PULLMAN, Wash. — A new mobile phone-based facial recognition application for dogs has the potential to significantly improve rabies vaccination efforts in endemic areas like Africa and Asia, according to a study on the research published in the journal Scientific Reports. Led by researchers at Washington State University, a team used the app to test its effectiveness at a rabies vaccination clinic in rural Tanzania where they microchipped, vaccinated and registered dogs. The technology proved remarkably accurate during a subsequent visit to surrounding villages once poor images and improperly recorded information were removed from its database. Using the app, operators identified 76.2% of vaccinated dogs and 98.9% of unvaccinated dogs. “Because domestic dogs are the main reservoir for human rabies, controlling human rabies globally requires the mass vaccination of dogs,” WSU Associate Professor Felix Lankester, the principal investigator of the study, said. “When carrying out mass vaccination, one of the major problems that we face is trying to identify which dogs have and haven’t been vaccinated. For example, microchips are too expensive to use at the scales needed to eliminate rabies, and collars can be removed by owners. We developed this app to see if facial recognition might work, and it’s showing great promise in helping us to achieve that goal.”

Rabies kills an estimated 60,000 people annually. Nearly all cases occur in Africa and Asia, and more than 99% are the result of dog bites. Systematic and consistent vaccination efforts, like those led by WSU’s Rabies Free Africa program, are effective at controlling the disease, but approximately 40% of dogs in an area must be vaccinated at any one time to achieve herd immunity and prevent sustained virus transmission. This makes the ability to accurately and efficiently identify vaccinated dogs vital for successful rabies elimination programs. The facial recognition algorithm used within the application, developed in collaboration with PiP My Pet, a company located in Vancouver, Canada, and researchers in WSU’s Paul G. Allen School for Global Health, identifies a dog by examining key components of its face and comparing it to images of the faces of other dogs in its archive of previously stored images. Images with the highest number of similar components are returned as possible matches, and the user must decide if there is a match.

The app depends on image quality and information about each dog, including its age, color and sex, being properly recorded. Before poor quality images and incorrect information were removed from the database, users were only able to match 65% of the vaccinated dogs. Lankester, who also serves as a director of Rabies Free Africa, said the app’s effectiveness could be improved with better technology – like newer smartphones with high-quality cameras – and additional operator training. In addition to its potential as a tool in identifying vaccinated dogs, the technology holds promise for use in other species, disease control efforts and research purposes where animals might need to be identified. Currently, users must be online to operate the facial matching component, however, Lankester said the team is also working to compress the size of the “engine” that drives the app’s matching facility to allow it to be downloaded and used offline, which would reduce the app’s reliance on internet access, which is not always available in more remote areas. “We’re not quite there yet, but I think with investment, the technology  can get there. I’m excited by its potential,” Lankester said, “but we have to find some funding to invest in pushing it forward. I welcome people to get in touch if they have funding ideas or would like to collaborate on this.”

Research published in Scientific Reports (Dec. 12, 2023):

https://doi.org/10.1038/s41598-023-49522-2 

Scores of Covid vaccines are in development. Four companies have manufactured the majority of doses. But that doesn't mean they are the best. P fizer/BioNTech. Moderna. Johnson & Johnson. AstraZeneca. These are the marquee names that spring to mind when you think of the vaccine companies at the forefront of the global fight against Covid-19. And for good reason: together they have manufactured the majority of the estimated 7 billion-plus Covid vaccine doses administered to date around the world.  But as regulators in the U.S., Europe, and around the world mull the most responsible way to expand vaccine eligibility to an even larger share of their populations — including to younger children, as the Food and Drug Administration (FDA) and Centers for Disease Control (CDC) have done this month by greenlighting Pfizer’s vaccine for kids 5 to 11 years of age — it’s time to confront an uncomfortable reality: The global health community still doesn’t know which of the hundreds of Covid vaccines currently in clinical and preclinical development are truly “the best.” That’s a shortcoming governments and the global health system need to address if they are to ensure that the next pandemic doesn’t knock the world on its heels to the extent the novel coronavirus has done.  Of the 128 Covid vaccines currently being clinically tested (21 of which have been cleared for use in general populations), Pfizer, Moderna, J&J, and AstraZeneca manufacture just four, according to the latest World Health Organization (WHO) data. Russia’s Sputnik V jab is being distributed in 39 countries with dozens of other markets potentially on the horizon; Sinovac and Sinopharm, both of China, have delivered nearly half of the world’s vaccine doses to date; Bharat Biotech in India won WHO emergency use approval for its Covid shot earlier this month. These are just a handful of the other companies with vaccines that are being given to people in many low- and middle-income countries. Another 194 candidates are in preclinical development in labs or being tested in animals.

These companies and their products are largely unknown outside of the life sciences industry, some academic institutions, and government-backed public health centers. But just because massive, globally established pharmaceutical companies and universities have fueled the world’s vaccine supply to date doesn’t mean they have created the best ones. Other vaccines may prove to be more effective, or safer, or more appropriate for a certain coronavirus variant or among certain age groups in the coming years as the march of SARS-CoV-2, the virus that causes Covid-19, is slowed and it becomes endemic. To be clear, I am not denigrating the safety and effectiveness of the most common and widely used Covid-19 vaccines. But as with so many other facets of public health, the pandemic has turned a glaring light on a long-festering problem: There is no unifying framework for what makes a vaccine “best.” This shortcoming inevitably leads to R&D and manufacturing imbalances down the line as dominant pharmaceutical players leverage their access to institutions and capital to leapfrog the vaccines-that-might-have-been.  The first essential step in addressing this failure is establishing a working definition of what constitutes “best” in vaccine development. Key data points to consider will include safety and effectiveness across coronavirus variants; short-, medium-, and long-term immunity; safety; and overall real-world health outcomes.

Should the level of neutralizing antibodies produced by a vaccine and their staying power be the metric by which it is judged? Should one vaccine be prioritized in certain geographic locations over another because different demographics respond to various jabs in different ways? Those questions need answers. Randomized clinical trials, the gold standard for sniffing out effective medicines, conducted early in the development process must be paired with monitoring real-world evidence for an evolving virus, like the data being collected in the 427 ongoing observational Covid-19 studies the WHO has tracked so far. Head-to-head clinical trials that compare one vaccine directly against another have their uses as well, but don’t address the underlying dilemma of defining exactly which qualities you’re looking for in a vaccine. And with hundreds of vaccine candidates, it’s simply implausible to conduct head-to-head studies of all of them. The focus, then, must be on ensuring that the vaccines most likely to be best are supported early. That requires a level of consensus on critical issues such as proper endpoints and goals, whether a vaccine is keeping people out of the hospital or preventing breakthrough infections, as well as more consistency in clinical trial enrollment, such as whether or not a study assesses a jab in children ages 5 to 12 rather than ages 5 to 11.  Beyond those clinical fundamentals, vaccines for Covid-19 or future infectious disease threats cannot reach their full potential without adequate investment and funding mechanisms guided by science.

The vaccines that have been granted approvals or authorizations to date have been the best funded, either through government programs such as Operation Warp Speed or private funding, while other candidates have stalled for lack of access to capital that can facilitate a quick manufacturing ramp-up to meet the moment’s need. If the same kind of global emergency were to emerge again, the system for advancing vaccine candidates currently in place would be no better — and perhaps would be even worse — without gargantuan ad hoc measures like Operation Warp Speed at play. By default, the current pandemic response has revealed a system where finance is a proxy for “best,” as if it was a betting market, rather than letting science guide resource allocation. There is currently no set of mutually recognized guidelines by which to rationalize investment in global vaccines, even though the U.S. will accept WHO “recognition” of a vaccine as sufficient for immunized travelers wishing to come into the country. But there is no prospect of the European Union, the United Kingdom, the U.S., and countries around the world working together “next time.” This is not a sustainable dynamic if we are to prevent, or at the very least mitigate, the public health catastrophes of tomorrow. Global health experts at the WHO and beyond had been warning that the world is fundamentally unprepared for such a calamitous event years before Covid-19 reared its head. And there has been a common theme in critiques of the existing vaccine infrastructure: There must be a mutual recognition around the world of rationalizing investment in vaccines of the future to outsmart yet-unknown pathogenic foes. Some of the world’s leading health organizations, such as the Coalition for Epidemic Preparedness Innovations (CEPI) and think tanks such as the Peterson Institute for International Economics, have already proposed common-sense improvements to the vaccine discovery, development, and evaluation process that can also make a tangible difference in manufacturing and distributing vaccines down the line. These are “portfolio” approaches meant to take a vaccine through its full life cycle, from discovery to real-world deployment. For instance, Peterson’s Reinhilde Veugelers, a professor in the department of management, strategy, and innovation at KU Leuven in Belgium, penned a report in March on the level of public and private investment necessary for both discovering and identifying the best vaccines in future pandemics and making sure they are effectively distributed across the globe.

“Because of the high risks associated with research projects, and the high social cost of failure, we need multiple vaccine candidates and technologies simultaneously. Public resources should especially support (or at least not bias against) the early stage, riskiest projects, which offer the greatest promises for big breakthroughs. Risks can be managed by diversifying and staging grants,” she writes. Veugelers goes on to note that this portfolio approach, which will almost inevitably mean government support for programs that will eventually fail, necessitates proactive investment at both the cheaper, early developmental stages and the far costlier long-term prospect of mass vaccine production and distribution. GAVI, the International Vaccine Institute, and CEPI laid out concrete steps on how to make sure promising vaccines are effectively distributed in an unpredictable pandemic environment in an article in the journal Nature Medicine:

• Standardize labeling of vaccines so they can be interchanged across countries and regions;
• Use date of production rather than expiration so shelf life can be tracked;
• Adopt three-dimensional bar coding to allow critical information to be updated;
• Employ standard indemnification and liability language that provides protection for manufacturers;
• Create no-fault compensation mechanism for serious adverse events related to vaccine administration;
• Harmonize regulations.

Pharmaceutical innovation requires constant reinvention and the ability to adapt to shifting circumstances while carrying forth the lessons learned from previous shortcomings. The world faces a tough set of choices on how to change existing structures of pandemic preparedness and vaccine development if it is to ward off the next worldwide threat. And that conversation must begin with the acknowledgment that the status quo cannot ensure a different, better outcome in the coming years and decades.

Mike Rea is a biopharmaceutical industry and innovation expert, a senior fellow at the Milken Institute’s FasterCures center, and the CEO of IDEA Pharma and Protodigm

You might assume that 95 out of every 100 people vaccinated will be protected from Covid-19. But that’s not how the math works. The front-runners in the vaccine race seem to be working far better than anyone expected: Pfizer and BioNTech announced this week that their vaccine had an efficacy rate of 95 percent. Moderna put the figure for its vaccine at 94.5 percent. In Russia, the makers of the Sputnik vaccine claimed their efficacy rate was over 90 percent. “These are game changers,” said Dr. Gregory Poland, a vaccine researcher at the Mayo Clinic. “We were all expecting 50 to 70 percent.” Indeed, the Food and Drug Administration had said it would consider granting emergency approval for vaccines that showed just 50 percent efficacy. From the headlines, you might well assume that these vaccines — which some people may receive in a matter of weeks — will protect 95 out of 100 people who get them. But that’s not actually what the trials have shown. Exactly how the vaccines perform out in the real world will depend on a lot of factors we just don’t have answers to yet — such as whether vaccinated people can get asymptomatic infections and how many people will get vaccinated.  Here’s what you need to know about the actual effectiveness of these vaccines.

What do the companies mean when they say their vaccines are 95 percent effective?

The fundamental logic behind today’s vaccine trials was worked out by statisticians over a century ago. Researchers vaccinate some people and give a placebo to others. They then wait for participants to get sick and look at how many of the illnesses came from each group. In the case of Pfizer, for example, the company recruited 43,661 volunteers and waited for 170 people to come down with symptoms of Covid-19 and then get a positive test. Out of these 170, 162 had received a placebo shot, and just eight had received the real vaccine. From these numbers, Pfizer’s researchers calculated the fraction of volunteers in each group who got sick. Both fractions were small, but the fraction of unvaccinated volunteers who got sick was much bigger than the fraction of vaccinated ones. The scientists then determined the relative difference between those two fractions. Scientists express that difference with a value they call efficacy. If there’s no difference between the vaccine and placebo groups, the efficacy is zero. If none of the sick people had been vaccinated, the efficacy is 100 percent. A 95 percent efficacy is certainly compelling evidence that a vaccine works well. But that number doesn’t tell you what your chances are of becoming sick if you get vaccinated. And on its own, it also doesn’t say how well the vaccine will bring down Covid-19 across the United States.

What’s the difference between efficacy and effectiveness?

Efficacy and effectiveness are related to each other, but they’re not the same thing. And vaccine experts say it’s crucial not to mix them up. Efficacy is just a measurement made during a clinical trial. “Effectiveness is how well the vaccine works out in the real world,” said Naor Bar-Zeev, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health. It’s possible that the effectiveness of coronavirus vaccines will match their impressive efficacy in clinical trials. But if previous vaccines are any guide, effectiveness may prove somewhat lower. The mismatch comes about because the people who join clinical trials are not a perfect reflection of the population at large. Out in the real world, people may have a host of chronic health problems that could interfere with a vaccine’s protection, for example. The Centers for Disease Control and Prevention has a long history of following the effectiveness of vaccines after they’re approved. On Thursday, the agency posted information on its website about its plans to study the effectiveness of coronavirus vaccines. It will find opportunities to compare the health of vaccinated people to others in their communities who have not received a vaccine....

The Milken Institute’s COVID-19 Treatment and Vaccine Tracker tracks the development of treatments and vaccines for COVID-19 (coronavirus). Explore the latest updates on the urgent race to develop a COVID-19 vaccine.

FasterCures, a center of the Milken Institute, has curated one of the most detailed and complete databases of treatments and vaccines for COVID-19. The database tracks over 500 therapeutics and prophylactics generated from publicly-available information from validated sources. The database is searchable, and information can be filtered by multiple criteria, including among others the stage of the therapy or vaccine, type of product, developer, and sponsors of clinical trials. Each entry contains important information such as dates and key milestones of each vaccine or therapy, and links to clinical trials and key research publications.

When visiting the site ensure you click on the spreadsheet link to access the searchable and filter options of the database tracker

Available at https://covid-19tracker.milkeninstitute.org/

Primate centers band together for study rejected by Operation Warp Speed. Primate researchers in the United States have banded together in a push for an ambitious monkey study that would do head-to-head comparisons of the leading COVID-19 vaccine candidates. Although 10 candidates are already undergoing large-scale tests in people, proponents of the monkey plan say those clinical trials may not deliver the comprehensive data needed to choose the safest and most effective vaccines. The comparison trial in monkeys, in contrast, could shed light in a matter of weeks on how the candidates stack up on measures including potential side effects, the strength of immune responses they trigger, and how well they protect against infection and disease. “We should take a cold, hard look at all of the data and ask ourselves, ‘What appears to work best?’” says Nancy Haigwood, who directs the Oregon National Primate Research Center and is a key advocate for the comparative monkey study.

The proposed monkey vaccine comparison faces hurdles: It would add to the pressure on the dwindling U.S. supply of research monkeys, potentially delaying research on other diseases, and it does not yet have funding. Haigwood says she expected the U.S. government would gladly support the effort, which would cost an estimated $10 million, compared with the $10 billion the Trump administration’s Operation Warp Speed has already devoted to a COVID-19 vaccine push. But facing a lack of interest by current Warp Speed officials, Haigwood and colleagues at the six other national primate research centers are now turning to the National Institutes of Health (NIH) for support. Most developers of the vaccine candidates in efficacy trials have already published how well each works in monkeys against a “challenge” with SARS-CoV-2—a deliberate exposure to the pandemic coronavirus that causes COVID-19. But the details of how the experiments were conducted and the ways the results were analyzed differ so profoundly that immunologist John Moore of Weill Cornell Medicine says he can’t make sense of how the candidates compare. “It’s comparing apples to oranges and bananas,” says Moore, who has co-authored a review, on preprint.org, that compares the various monkey studies. 

The human vaccine trials, for their part, are likely to yield only preliminary signals of efficacy over the next few months, not clear-cut evidence that one or more is safe and protects people. “We’re going to get data dribbling in from clinical trials,” says Haigwood, a veteran AIDS vaccine researcher. The data from the many human trials, some in multiple countries, will also be tough to compare. Jay Rappaport, who heads the Tulane National Primate Research Center, notes the trial populations differ and are infected by different variants of SARS-CoV-2. In addition, the human trials—as with the monkey experiments—often use different assays to measure immune responses. “There’s so much variation in the primate studies, but there’s even more variation in the human studies,” Rappaport says. In contrast to the human trials that must wait for enough participants to become naturally infected to gauge a vaccine’s worth, Haigwood says, monkey challenge studies could deliver definitive results quickly. She says the monkey comparison could start as soon as this month and would require only about 6 weeks to vaccinate animals, challenge them, and assess their immune responses and levels of protection...

BioNTech and Pfizer have started a rolling submission of their COVID-19 vaccine BNT162b2 to the European Medicines Agency (EMA). The news comes days after EMA named AstraZeneca's AZD1222 as the first COVID-19 vaccine to start the rolling review process. The EMA uses rolling reviews to start assessing data on an experimental candidate before all the evidence needed to make a final decision is available, cutting the time it takes to decide whether to approve a prospect once the pivotal clinical trial results are submitted to the agency. The pressing need for COVID-19 vaccines potentially makes the mechanism important to the current crisis. After receiving the first part of a rolling submission, the EMA’s Committee for Medicinal Products for Human Use has begun evaluating the preclinical evidence on mRNA vaccine BNT162b2. The rolling review format provides opportunities to file additional data before the complete application. Each cycle typically requires a two-week review. The duration of the review of the final application will depend on the proportion of data already assessed by EMA under the rolling review. 

The EMA accepted BNT162b2 for rolling review on the strength of the preclinical and early clinical data on the vaccine. BioNTech and Pfizer have linked BNT162b2, which encodes a SARS-CoV-2 spike glycoprotein, to antibody and T-cell responses in people dosed in early-phase trials. The data led the partners to start a phase 3 clinical trial. That trial has now enrolled around 37,000 participants at sites in countries including the U.S., Brazil, South Africa and Argentina, with centers in Turkey coming online to help push BioNTech and Pfizer to their enrollment target of 44,000 subjects. More than 28,000 participants have received their second dose. BioNTech and Pfizer originally planned to enroll 30,000 subjects. The enrollment figures suggest BioNTech and Pfizer are closing in on the release of top-line data from the trial. Exactly how long the partners need to wait for efficacy data will depend on the extent to which participants have been exposed to the virus and the effectiveness of the vaccine. BioNTech and Pfizer are set to perform interim efficacy analyses when there are 32, 62, 92 and 120 COVID-19 cases in the trial...

Data on past trials raises concerns for University of Massachusetts and Mt Sinai researchers that COVID-19 drugs and vaccines won't be tested in people over 65, who need them most. Americans over 65 were excluded from half of all US clinical trials of drugs and all trials for vaccines - including those for COVID-19 - from October of last year until June 1, 2020, new research reveals. People over 65 are the most likely to develop severe COVID-19 and die of the devastating viral infection.  Yet they have been systematically left behind 50 percent of the time as scientists tried experimental therapies in trials of drugs for any condition, including those for coronavirus, like remdesivir, which might have saved the lives of thousands of older Americans. 

Older people were left out of 100 percent despite the fact that they will likely be the first Americans to receive a shot once one is FDA-approved - far ahead of the young people  vaccines were tested in.  In ordinary circumstances, older people face higher risks of complications if they are enrolled in trials of experimental drugs and vaccines, so they may be excluded. But in the unprecedented scenario of the COVID-19 pandemic, researchers at University of Massachusetts and the Icahn School of Medicine at Mount Sinai worry  that the risks of giving older people treatments and shots with unknown effects may outweigh those of testing them in clinical settings. 'To be sure, some exclusions are needed to protect the health and safety of older adults - such as poorly controlled comorbidities,' said senior study author Dr Sharon Inouye, director of the  Brain Aging Center at Hebrew SeniorLife, at the University of Massachusetts. However, many [exclusions] are not well-justified, and appear to be more for expediency or convenience of the trialists.' People over 65 account for just nine percent of the global population, but more than 80 percent of COVID-19 deaths thus far have been people in this older age group.  

Although the first case of coronavirus in the US was not identified until late January 2020, the researchers looked at 847 trials registered to ClinicalTrials.gov from October 1, 2019 until June 1, 2020.  Of the trials, 23 percent had age cut-offs. The trials primarily cited concerns that older enrollees would not comply with treatment of vaccine regimens. Others wrote they believed it would be too difficult to get informed consent from older participants.  The researchers then combined the number of studies that explicitly excluded older Americans and those that had other exclusions likely to make the inaccessible to older adults.  In total, 53 percent of all drug trials were likely to have very low or no enrollment of adults over 65.  And 100 percent of vaccine trials were estimated to exclude older adults.  As a consequence of the time period, most trials included in the study were not for COVID-19 drugs and vaccines specifically.  But, 'our concern is more than theoretical,' the study authors wrote.  'Even without stated age-based exclusions, several recently published clinical trials of COVID-19 treatments had young age ranges, such as one recent study with a median age of only 40 years, meaning there would be no or few participants over age 75. If the older age group is excluded from vaccine trials, efforts to ensure effectiveness, titrate dosage or frequency, and assess adverse effects in the group most vulnerable to COVID-19 will not be possible.'...

Study cited published in JAMA (Sept. 28, 2020):

https://doi.org/10.1001/jamainternmed.2020.5084

The Covid-19 vaccine trial designed by Pfizer Inc. and its German partner BioNTech SE may allow them to find whether their shot works before their fastest-moving rivals. The companies plan a first look after a mere 32 coronavirus infections have accumulated in their massive 44,000-person trial. That case total could be reached as soon as Sept. 27, according to Airfinity Ltd., a London-based analytics firms tracking vaccine trials. Pfizer has also given itself four chances to get a preliminary result, before reaching the final goal of 164. Some trial experts say the company appears to be looking for a leg up in a race against frontrunners such as Moderna Inc. and AstraZeneca Plc to be first with a vaccine. “I’ve never seen a trial where there were four interim analyses; that may be the Olympic record,” said Eric Topol, editor-in-chief of Medscape, a website offering clinical information for health-care professionals, and director of the Scripps Research Translational Institute in La Jolla, California. “It’s obvious why it is being done: so you can just keep looking at the data to try to win a race.”

A wide range of symptoms and severity makes the evaluation of Covid-19 vaccines tricky. The U.S. Food and Drug Administration has said that to be approved, vaccines should cut the number of symptomatic cases by half. Yet documents released by the drugmakers show each has its own approach to defining which symptoms count, and when to count them. Big drug studies usually allow a panel of monitors to get an early peek at the data once or twice before the planned end. The panel can stop the trial early if a treatment is judged overwhelmingly effective -- or alternatively, a total dud. Four early looks may give Pfizer an “easy route” to making sure it has results soon, said Marie-Paule Kieny, a former World Health Organization official who’s now a research director at the French health-science institute Inserm. “It seems that there are different levels of stringency,” she said in an interview. “I wouldn’t say that Pfizer-BioNTech comes out as a star of stringency.” Moderna, working with the U.S. National Institute of Allergy and Infectious Diseases, won’t dive in until 53 cases have occurred; its ultimate goal is to make a judgment at 151 diagnoses. Cancer powerhouse AstraZeneca, collaborating with the University of Oxford, will take its first look at 75 cases, and not again until the trial is complete with 150.

“All trials have set the bar quite low for what they test against,” said Rasmus Bech Hansen, Airfinity’s chief executive officer. Pfizer’s trial was designed to evaluate its vaccine candidate “as fast as possible,” said Amy Rose, a spokeswoman, in an email. The company has worked with government scientists to develop best practices for testing and based its schedule for interim analyses on the vaccine’s “strong profile” in early human trials and animal tests, she said. Moderna’s plan was agreed upon with U.S. regulators, and the company has been open about the numbers since before the trial began in late July, spokesman Ray Jordan said in an email. Case totals for interim analysis were based on probabilities of success and “were not selected based on timeframes,” he said. AstraZeneca said its trials are conducted under regulatory oversight and its plans have evolved over time to make sure they produce robust information in a timely way. All the companies said their trials will continue beyond points such as a preliminary readout or potential authorization. Pfizer says its study will likely yield conclusive results in October. None of the drugmakers will likely know whether their vaccines lower hospitalizations until February, according to Airfinity. But it’s the earlier assessments that have observers most concerned.

Public health experts warn that the wide-reaching emergency use program poses risks.  China has taken a shortcut in the global sprint to develop and deliver vaccines for the novel coronavirus. Sinopharm, the state-owned company developing two of China’s leading vaccine candidates, told China National Radio on Monday that it has already vaccinated hundreds of thousands of Chinese citizens — even though the company’s phase 3 clinical trials have not yet concluded. Individuals received one of two Sinopharm vaccines in development in an emergency use program launched by the Chinese government in late July, which also authorized a third vaccine, CoronaVac, developed by the privately owned drugmaker Sinovac Biotech. Under Chinese vaccine law, such authorization is allowed within a certain scope and time frame during a health emergency. China’s top vaccine official mentioned front-line medical workers and customs officials when he first announced the program, implying these high-risk groups had been prioritized to receive the still-experimental vaccines.

Phase 3 clinical trials, which look at the efficacy of a vaccine candidate at preventing a virus from spreading in a community, for the three Chinese vaccines had just begun overseas when they were approved for emergency use domestically. In July, Sinopharm initiated phase 3 trials for its two vaccine candidates in the United Arab Emirates; one of the vaccines also began trials in Morocco and Peru in August, according to the New York Times vaccine tracker. Sinovac launched CoronaVac’s phase 3 trials in July in Brazil, followed by Indonesia the following month. (The trials are being conducted outside of China because the vaccines’ protectiveness can be better evaluated in regions where Covid-19 transmission is high.) China and Russia are the only countries that have provisionally greenlit vaccines that have yet to be deemed safe and effective through phase 3 trials. In the US, the Centers for Disease Control and Prevention has told states to prepare to distribute vaccines to high-risk groups by the end of October or early November, stirring concerns that the vaccine approval process may be politicized ahead of the 2020 election. However, nine leading vaccine developers pledged to not submit their vaccines for approval until data from phase 3 trials shows that they meet predetermined safety and efficacy thresholds. No Chinese companies signed the pledge. 

So far, China has not reported any serious issues with its emergency vaccine program. But vaccine experts told Vox that skipping or shortening phase 3 trials is risky and could subject citizens to an ineffective or unsafe vaccine. The risks are even higher in China, where vaccine producers have a history of scandals and the media is largely unable to play a watchdog role because of state control. Although transmission has reportedly been very low in China since February, controlling local hot spots is still a priority for the government, said Yanzhong Huang, a professor of global health at Seton Hall and author of Toxic Politics, an examination of China’s environmental health crisis. “They have this strong incentive to develop vaccines to show Chinese high-tech capacity, and also [to] give people the sense of national pride,” Huang added.

Here’s what we know about how China’s emergency vaccine program is playing out so far. In the crowd of pharmaceutical companies that have jumped into the vaccine effort, Chinese companies got a swift and aggressive start. Of the 211 vaccines in development worldwide as of September 11, nine vaccines are in phase 3 trials, and four of the nine are from Chinese companies. These trials allow scientists to determine the vaccines’ efficacy and identify side effects that may not have appeared in phase 1 or phase 2 trials. But rather than waiting for trial results, the Chinese government started allowing certain workers to be vaccinated on a separate track...

Dozens of research groups around the world are playing the long game, convinced that their experimental vaccines will be cheaper and more powerful than the ones leading the race today. Seven months into the coronavirus pandemic, with more than 30 vaccines rapidly advancing through the rigorous stages of clinical trials, a surprising number of research groups are placing bets on some that have not yet been given to a single person. The New York Times has confirmed that at least 88 candidates are under active preclinical investigation in laboratories across the world, with 67 of them slated to begin clinical trials before the end of 2021. Those trials may begin after millions of people have already received the first wave of vaccines. It will take months to see if any of them are safe and effective. Nevertheless, the scientists developing them say their designs may be able to prompt more powerful immune responses, or be much cheaper to produce, or both — making them the slow and steady winners of the race against the coronavirus. “The first vaccines may not be the most effective,” said Ted Ross, the director of the Center for Vaccines and Immunology at the University of Georgia, who is working on an experimental vaccine he hopes to put into clinical trials in 2021.

Many of the vaccines at the front of the pack today try to teach the body the same basic lesson. They deliver a protein that covers the surface of the coronavirus, called spike, which appears to prompt the immune system to make antibodies to fight it off. But some researchers worry that we may be pinning too many hopes on a strategy that has not been proved to work. “It would be a shame to put all our eggs in the same basket,” said David Veesler, a virologist at the University of Washington. In March, Dr. Veesler and his colleagues designed a vaccine that consists of millions of nanoparticles, each one studded with 60 copies of the tip of the spike protein, rather than the entire thing. The researchers thought these bundles of tips might pack a stronger immunological punch. When the researchers injected these nanoparticles into mice, the animals responded with a flood of antibodies to the coronavirus — much more than produced by a vaccine containing the entire spike. When the scientists exposed vaccinated mice and monkeys to the coronavirus, they found that it completely protected them from infection. The researchers shared their initial results this month in a paper that has yet to be published in a scientific journal. Icosavax, a start-up company co-founded by Dr. Veesler’s collaborator, Neil King, is preparing to begin clinical trials of the nanoparticle vaccine by the end of this year. U.S. Army researchers at the Walter Reed Army Institute have created another spike-tip nanoparticle vaccine, and are recruiting volunteers for a clinical trial that they also plan to start by the end of 2020. A number of other companies and universities are creating spike-tip-based vaccines as well, using recipes of their own.

Immune punch

Long-term antibody responses and neutralizing activities following SARS-CoV-2 infections have not yet been elucidated. We quantified immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of six months following COVID-19 disease onset in 349 symptomatic COVID-19 patients, which were among the first world-wide being infected.

The positivity rate and magnitude of IgM-S and IgG-N responses increased rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset were associated with virus control and IgG-S titers correlated closely with the capacity to neutralize SARS-CoV-2. While specific IgM-S/N became undetectable 12 weeks after disease onset in most patients, IgG-S/N titers showed an intermediate contraction phase, but stabilized at relatively high levels over the six months observation period. At late time points the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies was still over 70%. Taken together, our data indicate sustained humoral immunity in recovered patients who suffer from symptomatic COVID-19, suggesting prolonged immunity.

Preprint available at medRxiv (July 24, 2020):

https://doi.org/10.1101/2020.07.21.20159178

Bill Gates is feeling optimistic that, with all the work being done to develop COVID-19 treatments and vaccines, there is an end to the pandemic in sight. Unfortunately, that end is still at least a year away, he told Wired's Steven Levy. "The innovation pipeline on scaling up diagnostics, on new therapeutics, on vaccines is actually quite impressive. And that makes me feel like, for the rich world, we should largely be able to end this thing by the end of 2021, and for the world at large by the end of 2022," Gates said. Gates says that he fears that in nations like Russia and China, the pressure to have a vaccine is so high that regulators may be allowing shots to be given to humans before the vaccines are known to be safe and effective. But the US FDA is not allowing such short-cuts, he said.

"We probably need three or four months — no matter what — of phase 3 data, just to look for side effects," Gates said. "The FDA, to their credit, at least so far, is sticking to requiring proof of efficacy." Last month, Gates told Business Insider's Hilary Brueck that he's confident that scientists will develop a vaccine that's "very effective and very safe" in part because there are so many vaccines currently in development: more than 160 worldwide. Two of the four speediest trials that are testing vaccines in humans right now are US-based, too: Moderna and Pfizer/BioNTech. Gates also told Brueck if the best vaccines are not shared worldwide, that COVID-19 will "just keep coming back." In the meantime, Gates predicts we're in for a rough fall and winter with the virus, even though this virus does not appear to be seasonal.  "The fall could be tough," he told Brueck. "We'll be indoors more. It will be colder. We know those are things that push the disease up."

New results hint at how to perfect ‘mucosal’ vaccines, which are delivered up the nose or down the throat. Delivery of COVID vaccines directly to the lungs and nose can stop SARS-CoV-2 infections in their tracks, according to a trio of new studies in monkeys. The research offers a boost to the wave of ‘mucosal’ COVID-19 vaccines now in development — and provides clues about how they might be improved. Until now, there has been little evidence that mucosal vaccines, which are taken by nose or mouth, shield people against infection any better than existing COVID-19 jabs do. Even so, some countries have already approved such vaccines, and key trials are under way in the United States, with others set to start. Together, the studies show that how and where vaccines are delivered can have a profound effect on the immunity generated and the protection conferred. The latest results also raise hopes that mucosal vaccines that offer ‘sterilising’ immunity — complete blockage of infection — could become a reality. “These studies are showing you can get near sterilising immunity,” says Akiko Iwasaki, an immunologist at the Yale School of Medicine in New Haven, Connecticut. "It’s not complete science fiction to think about developing vaccines that would stop transmission and infection....

Probably many people who watched or participated in the June 28 virtual US Food and Drug Administration (FDA) advisory committee meeting about updating COVID-19 vaccines could agree on 1 point, made by the agency’s Peter Marks, MD, PhD: “It is science at its hardest.” The FDA convened its Vaccines and Related Biological Products Advisory Committee (VRBPAC) to discuss whether to add an Omicron component to boosters for the fall. In order to have enough doses by early October, “we will need to very rapidly move to let companies know what that selection will be,” Marks reminded the panelists. (How many doses will be enough isn’t clear—as of June 30, only 51.1% of fully vaccinated US adults aged 18 years or older had received 1 booster shot, while only 27% of fully vaccinated adults aged 50 years or older, for whom a second booster is recommended, had received 2, according to government data.) Omicron, which the World Health Organization (WHO) classified as a variant of concern (VOC) in November 2021, is the first VOC that can evade the immune system, resulting in lower vaccine effectiveness, the WHO’s Kanta Subbarao, MBBS, MPH, told committee members. Even so, she noted, after a booster dose, the available prototype vaccines, which are based on the ancestral SARS-CoV-2 index virus strain that has long been undetectable among circulating viruses, continue to protect people against serious illness and death. After a day of listening to presentations by Subbarao, director of the WHO’s Collaborating Centre for Reference and Research on Influenza in Melbourne, and scientists from the FDA, the Centers for Disease Control and Prevention (CDC), and 3 vaccine manufacturers—Moderna, Pfizer, and Novavax—the advisory committee voted 19-2 to recommend inclusion of a SARS-CoV-2 Omicron component for COVID-19 booster vaccines this fall.

Less than 48 hours later, the FDA, which usually follows advisory committee recommendations after such lopsided votes, announced that manufacturers seeking to update COVID-19 vaccines should add a spike protein component of the Omicron subvariants BA.4 and BA.5 (which differ only outside the spike protein) to their prototype vaccines to make bivalent boosters that can be used beginning this fall. “[W]e have not advised manufacturers to change the vaccine for primary vaccination, since a primary series with the FDA-authorized and approved COVID-19 vaccines provide a base of protection against serious outcomes of COVID-19 caused by circulating strains of SARS-CoV-2,” Marks, director of the agency’s Center for Biologics Evaluation and Research, said in the announcement. Yet the data presented at the VRBPAC meeting were about experimental bivalent boosters that combined prototype vaccines with the spike protein of the original Omicron variant, BA.1. When the advisory committee reconvened after lunch, Marks noted that in the week ending June 25, BA.4 and BA.5 represented more than half of US circulating SARS-CoV-2 variants for the first time, according to newly released CDC data. By the week ending July 2, BA.5 alone represented 53.6% of US circulating SARS-CoV-2 variants, while BA.4 represented 16.5%, according to the CDC. CDC data show that BA.1, which represented about a third of circulating US variants on March 26, was undetectable by May 21—an illustration of just how quickly SARS-CoV-2 is evolving.....

Background

The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear.

Methods

We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status.

Results

Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant.

Conclusions

Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)

Published in NEJM (July 21, 2021):

https://doi.org/10.1056/NEJMoa2108891 

“We should be reassured by the care taken by independent regulators to protect the public," AstraZeneca's CEO said. Two major studies of vaccines against Covid-19, both paused because of potential safety concerns, are set to restart, the companies running them said Friday. “The restart of clinical trials across the world is great news as it allows us to continue our efforts to develop this vaccine to help defeat this terrible pandemic,” Pascal Soriot, AstraZeneca’s CEO, said in a statement. “We should be reassured by the care taken by independent regulators to protect the public and ensure the vaccine is safe before it is approved for use.” “We as a company have found no evidence the vaccine candidate caused the event, and we have agreed to restart the study,” Paul Stoffels, the chief scientific officer at Johnson & Johnson, said in an interview. In both cases, new documents describing potential risks for both researchers and volunteers have been prepared, and must be approved by a centralized institutional review board, one of several groups charged with protecting patients in the trial.

AstraZeneca’s restart was first reported by the Wall Street Journal; the impending restart of the J&J study was first reported by the Washington Post.  AstraZeneca stopped administering new doses of its vaccine on Sept. 6, a step first reported by STAT, after a participant in the trial developed neurological symptoms. These symptoms were reportedly caused by transverse myelitis, a serious spinal cord condition.  AstraZeneca said in its statement that the voluntary pause was part of its standard review process for safety events, and that such pauses are not unusual. It said reviews from the trial’s independent monitoring  committees indicated it was safe for the trials to resume, and that this conclusion was supported by international regulators.  A study of the vaccine in the U.K. restarted on Sept. 12, and shortly thereafter studies in Brazil and South Africa resumed. A study in Japan restarted earlier this month. But the Food and Drug Administration decided to further investigate the case, and the U.S. trial has remained on hold for more than a month.

A trial of another vaccine, being developed by Johnson & Johnson, was paused on Oct. 11.  According to a person familiar with the matter, a male volunteer in his twenties had a cerebral hemorrhage and transverse sinus venous thrombosis. The Washington Post, citing two sources, said this case was a stroke. Stoffels said that the case was reviewed by external experts, with reports made continuously both by the study’s data and safety monitoring board, an outside panel overseeing the studies, and the FDA. A final report was sent to the agency late this week. Circumstances with the patient made the process slower than it might have been. “We worked as hard as we could,” Stoffels said. “We would not put more people at risk until we knew what the cause or relationship would be.” The J&J study could begin enrolling patients again early next week, Stoffels said. He noted that the study already includes a large number of sites, and that the company will be making sure the participants are diverse in their ethnic background, their age, and any disorders they have that could make them higher risk. The J&J effort is important because it is the only one of the major vaccine efforts to be testing a single dose, and the company has made the main goal of its study to test whether the vaccine prevents severe or moderate Covid-19, not just symptomatic cases of the disease.

The presentation summarizes the global efforts of W.H.O. to support the development, test, and manufacture of  COVID-19 vaccine in record times. The time for approval of a vaccine averages  10 years. However, the process is expected to be reduced by more than 5 times for COVID-19. This presentation, updated as of October 6, 2020,  summarizes the W.H.O. global efforts towards this goal, and also provides and excellent summary of the vaccine development process.

As of today, at least 213 COVID-19 vaccines are under development, including 178 preclinical candidates and 35 vaccines in human trials. Nine  vaccines have already entered advanced Phase III trials. With typical approval rates of 7% for preclinical candidates, and 20% for those entering human trials, more than 30 vaccines  against SARS-CoV-2 could be approved in the following years, and about two of them  in the following months.

The White House has blocked the Food and Drug Administration (FDA) from enacting stricter federal guidelines on the emergency release of a potential coronavirus vaccine,  The New York Times reported on Monday. The FDA first submitted the proposal for new guidelines in late September, but they were immediately rebuffed by President Trump and top officials who worried it would delay the release of a vaccine as Trump's "Operation Warp Speed" has sought to quickly move one through the approval process. According to the Times, the new guidance included the recommendation that volunteers in the vaccine clinical trials be followed for around two months after receiving their final dose before an official vaccine authorization is granted. The recommendation is part of an effort to make sure an approved vaccine is safe.  The Times reports that specific part of the proposed guidelines was the sticking point for White House officials. The report comes as the FDA is looking to reassure the public that it is following the science and will make sure any vaccine is safe and effective before authorizing it amid fears of political pressure from Trump.   Trump had signaled he may not approve the guidelines after they were proposed.

“We’re looking at that. That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” Trump told reporters at a White House briefing when asked if he agreed with the FDA's plan. “Why would [companies] have to be adding great length to the process? We want to have people not get sick. The vaccine is very important,” Trump said, adding, “I think that was a political move more than anything else.”  It marks another instance of Trump and the White House breaking with top health officials on public health guidelines and his assessments about the threat posed by the virus.  Meanwhile, some have raised questions about the safety of a vaccine.  Last month nine pharmaceutical companies signed a joint pledge not to approve any vaccine without confidence in its safety and efficacy.

All COVID-19 vaccine developers can use the network of five laboratories working together as part of centralised network to reliably assess and compare immunological responses generated by COVID-19 vaccine candidates.   Five laboratories initially selected to work together as part of centralised network to reliably assess and compare immunological responses generated by COVID-19 vaccine candidate. Global group will minimise variation between individual lab analyses to enable uniform way of evaluating and identifying the most successful candidates. All COVID-19 vaccine developers (both CEPI-funded and non-CEPI funded) can use the network. In order to monitor interest and adjust the testing capacity, we are requesting that all COVID-19 vaccine developers interested in using CEPI’s centralised laboratory network complete this short survey. For any COVID-19 vaccine developer ready to submit their samples to the network, please complete our Sample Analysis Request Form. 

2 October 2020, Oslo, Norway –The Coalition for Epidemic Preparedness Innovations (CEPI) has today announced partnerships with five clinical sample testing laboratories to create a centralised global network to reliably assess and compare the immunological responses generated by COVID-19 vaccine candidates. Located across multiple regions globally, the laboratories initially selected for this vaccine-assessment network are: Nexelis (Canada) and Public Health England (PHE, UK), VisMederi Srl (Italy), Viroclinics-DDL (The Netherlands), icddr,b (formerly International Centre for Diarrhoeal Disease Research, Bangladesh), and Translational Health Sciences and Technological Institute (THSTI, India). The network will use the same testing reagents—originating in the labs of Nexelis and PHE—and follow common protocols to measure the immunogenicity of multiple COVID-19 vaccine candidates (both CEPI-funded and non-CEPI funded developers). This approach will ensure uniformity in assessment and informed identification of the most promising vaccine candidates. CEPI is actively negotiating with additional laboratories to participate in this network.

Advantages of centralising immunological response assessment

Typically, the immunogenicity of potential candidate vaccines is assessed through individual laboratory analyses, aiming to determine whether biomarkers of immune response—such as antibodies and T-cell responses—are produced after clinical trial volunteers receive a dose(s) of a vaccine candidate. However, withover 320 vaccine candidates against COVID-19 currently in development, there are likely to be numerous differences in data collection and evaluation methods. This includes potential variation in the range of correlates of immunity being measured by laboratories. Technical differences in how and where samples are collected, transported and stored can also occur, impacting the quality and usefulness of the data produced and making comparisons between measurements in individual laboratories difficult. In addition, with the wide range of COVID-19 vaccine approaches and technologies currently being deployed (e.g., recombinant viral vectors, live attenuated vaccines, recombinant proteins and nucleic acids), standard evaluation of the true potential of these vaccine formulations becomes very complex.

Through centralising the analysis of samples obtained from trials of COVID-19 vaccine candidates, the new clinical-sample-testing network will minimise variation in results obtained, which could otherwise arise due to such technical differences when carrying out independent analysis. The samples from participating vaccine developers will instead be tested in the same group of laboratories using the same methods, therefore, removing much of the inter-laboratory variability and allowing for head-to-head comparisons of immune responses induced by multiple vaccine candidates.

Supporting global COVID-19 vaccine development

Through this new network, up to the limit of programme funding, eligible COVID-19 vaccine developers (both CEPI-funded and non-CEPI funded developers) can use the laboratories, without per sample charges, to analyse the immune response elicited by their COVID-19 vaccine candidates in preclinical, Phase I and Phase IIa studies. Data obtained on the immunogenicity of CEPI-funded vaccine candidates will be used to inform and advance CEPI’s COVID-19 vaccine portfolio by providing quick and accurate evaluation of its candidate vaccines. By opening the sample testing network to other COVID-19 vaccine programmes, CEPI also aims to ensure that all eligible developers—regardless of their size—can benefit from this analysis. Certain commitments may be required for eligibility, such as making timely publication of sample testing results and sharing data that will be produced on the immunogenicity of COVID-19 vaccine candidates to facilitate future regulatory decisions. The number of samples available for testing per developer may be limited depending on response...

Business Insider asked five infectious-disease experts when they'd feel confident getting a coronavirus vaccine. Experts who have been studying viruses and vaccines for decades don't agree on when they'll get a vaccine.The drugmakers behind the leading COVID-19 vaccine candidates expect conclusive results by the end of this year, potentially as soon as October, that demonstrate whether the shots prevent disease. These final studies, called phase-three trials, are enrolling tens of thousands of volunteers to determine whether or not these experimental vaccines outperform a placebo group. But it's unclear how comprehensive that data will be. In interviews with five experts in vaccines and virology, Business Insider asked experts how they plan to assess the data and ultimately decide for themselves if they'd get the shot.

Some were confident they'd get vaccinated if US regulators determined it was safe and effective and recommended it for their age group. While they generally hope a vaccine will be highly effective, they'd also settle for a shot that's less effective, more in line with the seasonal influenza vaccine that can be around 50% effective some years. Others want more specific data, either that represents their specific demographic group or long-term follow-up results for safety and effectiveness. Here's what it would take for five infectious-disease experts to feel confident getting a COVID-19 vaccine.

Virologist Richard Condit: 'I'm going to trust the people running the trials.'

Richard Condit has been studying viruses for several decades in the lab. While he's well-versed in virology and infectious diseases, his primary expertise isn't vaccine development. That leads him to trust the scientists most closely involved with these shots, he said. "I'm going to trust the people running the trials," he said. "If they say we have enough disease in the control group, so that we can say statistically this is a certain acceptable level of efficacy, and we haven't seen significant adverse effects, I'm probably going to go for it."  The 72-year-old retired virologist said he's closely watching for signs of political pressure on vaccine decisions. Condit said he trusts the pharmaceutical companies along with the scientists at the Centers for Disease Control and Prevention and the Food and Drug Administration, but he does not trust the Trump administration. "I trust what [Trump] would call the 'deep state,'" he said. "I don't say I'll go ahead and get the vaccine without reservation," Condit said. "There's a little bit of nervousness associated with that, but I'm 72 years old. I'm very healthy, but age-wise, I'm in a group that has sufficiently high risk ... There's significant probability that the benefit of being vaccinated exceeds the risk of that crappy outcome from getting the disease." Condit said ideally a coronavirus vaccine would be 80% or 90% effective. But he'd also still take one that was less effective but still helpful, such as one that reduces the chance of getting COVID-19 by 50%. "If I can get a vaccine that reduces my chances of getting this crappy disease by 50%, I'll take it," he said, adding a 50% effective vaccine "is probably a stopgap measure that makes us safer but not completely safe."...

The National Medical Association committee is meant to safeguard against any unscientific guidance from the CDC and FDA. As trust in federal health agencies has withered over the last few months, a group of Black physicians has been working on an antidote: creating their own expert task force to independently vet regulators’ decisions about Covid-19 drugs and vaccines as well as government recommendations for curbing the pandemic. Organized by the National Medical Association — founded in 1895 as an answer to racist professional societies excluding Black doctors — the committee is meant to safeguard against any unscientific guidance from the Centers for Disease Control and Prevention and the Food and Drug Administration. “It’s necessary to provide a trusted messenger of vetted information to the African American community,” said Leon McDougle, a family physician and president of the NMA. “There is a concern that some of the recent decisions by the Food and Drug Administration have been unduly influenced by politicians.”

Just one of the examples he gave was the agency’s go-ahead to use hydroxychloroquine against Covid-19 even though there was no reliable evidence that it worked, and some indication that it could cause heart damage. The FDA later back-tracked and revoked the authorization. McDougle frames the new task force as a way to address the suspicion that has sprouted up around Covid-19 vaccines. Some worry that, in being developed at “warp speed,” the shots might not be safe or properly tested before they’re approved, and the anxiety is only heightened for those who’ve been alienated by the medical system. That’s part of the reason that certain patients of color are especially wary of taking part in the clinical trials — and those concerns may well persist even if adequate studies are done and a vaccine hits the market. “I think this will help to increase uptake in the African American community, if members of our task force give it the green light,” McDougle said. But he emphasized that their stamp of approval would come only if data show that the vaccine is, in fact, effective and safe. They’ll also be evaluating how well the clinical trial participants represent the demographic breakdown of the American population, as well as the fairness of the federal plans to distribute a vaccine — both of which are especially important given the disproportionate impact that the pandemic has had on Black, Latino, and Native American communities.

“There is a need for this task force. We need a trusted organization to take the lead on this effort,” said emergency physician Uché Blackstock, the founder and CEO of the consulting firm Advancing Health Equity, who is not a member of the NMA. “What we’ve seen in terms of political interference in the FDA and CDC has really undermined what little trust the Black community had.” While the NMA may not be a household name for the lay public, Blackstock added, “because they are an organization of Black physicians led by Black physicians, what they ultimately say and recommend will have significant influence on whether people take the vaccine or not.” (McDougle didn’t know how many members the NMA currently has, and the executive director did not respond to repeated requests for comment.) The task force’s leaders are still figuring out exactly how it will work. When asked what would happen if the FDA authorizes the use of a product without releasing the full data to support it — as was the case with the antiviral drug remdesivir in May — McDougle said that because some of the members are also involved with federal committees, he hopes that they would have access to those statistics, and that there wouldn’t be much of a lag between a governmental decision and the NMA’s review.  To scholars who study vaccine acceptance, the task force has the potential to either increase immunization rates or deepen mistrust. Under normal circumstances, Saad Omer, director of the Yale Institute for Global Health, would prefer that everyone simply look to the FDA and the CDC’s Advisory Committee on Immunization Practices. “As a public health professional, the more the mainstream process is followed, the better,” he said...

High-profile COVID-19 vaccines developed in Russia and China share a potential shortcoming: They are based on a common cold virus that many people have been exposed to, potentially limiting their effectiveness, some experts say. CanSino Biologics’ vaccine, approved for military use in China, is a modified form of adenovirus type 5, or Ad5. The company is in talks to get emergency approval in several countries before completing large-scale trials, the Wall Street Journal reported last week. A vaccine developed by Moscow’s Gamaleya Institute, approved in Russia earlier this month despite limited testing, is based on Ad5 and a second less common adenovirus. “The Ad5 concerns me just because a lot of people have immunity,” said Anna Durbin, a vaccine researcher at Johns Hopkins University. “I’m not sure what their strategy is … maybe it won’t have 70 percent efficacy. It might have 40 percent efficacy, and that’s better than nothing, until something else comes along.”

Vaccines are seen as essential to ending the pandemic that has claimed over 845,000 lives worldwide. Gamaleya has said its two-virus approach will address Ad5 immunity issues.  Both developers have years of experience and approved Ebola vaccines based on Ad5. Neither CanSino nor Gamaleya responded to requests for comment. Researchers have experimented with Ad5-based vaccines against a variety of infections for decades, but none are widely used. They employ harmless viruses as “vectors” to ferry genes from the target virus — in this case the novel coronavirus — into human cells, prompting an immune response to fight the actual virus. But many people already have antibodies against Ad5, which could cause the immune system to attack the vector instead of responding to the coronavirus, making these vaccines less effective. Several researchers have chosen alternative adenoviruses or delivery mechanisms. Oxford University and AstraZeneca based their COVID-19 vaccine on a chimpanzee adenovirus, avoiding the Ad5 issue. Johnson & Johnson’s candidate uses Ad26, a comparatively rare strain. Dr. Zhou Xing, from Canada’s McMaster University, worked with CanSino on its first Ad5-based vaccine, for tuberculosis, in 2011. His team is developing an inhaled Ad5 COVID-19 vaccine, theorizing it could circumvent pre-existing immunity issues. “The Oxford vaccine candidate has quite an advantage” over the injected CanSino vaccine, he said. Xing also worries that high doses of the Ad5 vector in the CanSino vaccine could induce fever, fueling vaccine skepticism.

“I think they will get good immunity in people that don’t have antibodies to the vaccine, but a lot of people do,” said Dr. Hildegund Ertl, director of the Wistar Institute Vaccine Center in Philadelphia.  In China and the United States, about 40 percent of people have high levels of antibodies from prior Ad5 exposure. In Africa, it could be has high as 80 percent, experts said.  Some scientists also worry an Ad5-based vaccine could increase chances of contracting HIV.  In a 2004 trial of a Merck & Co Ad5-based HIV vaccine, people with pre-existing immunity became more, not less, susceptible to the virus that causes AIDS. Researchers, including top U.S. infectious diseases expert Dr. Anthony Fauci, in a 2015 paper, said the side effect was likely unique to HIV vaccines. But they cautioned that HIV incidence should be monitored during and after trials of all Ad5-based vaccines in at-risk populations.  Gamaleya’s vaccine will be administered in two doses: The first based on Ad26, similar to J&J’s candidate, and the second on Ad5. Alexander Gintsburg, Gamaleya’s director, has said the two-vector approach addresses the immunity issue. Ertl said it might work well enough in individuals who have been exposed to one of the two adenoviruses.

Through Operation Warp Speed, the U.S. has backed seven vaccine candidates with $11 billion, securing preorders for some 800 million doses. Scientists, drugmakers and governments are moving with unprecedented haste to deliver a vaccine to protect against the new coronavirus. The fastest of them have already delivered early data from human studies, and further results from others should come quickly as the year progresses. The goal, at least in the U.S., is to have a vaccine ready for use in some fashion by the end of the year, or early next. Doing so would be a scientific feat with few parallels. No vaccine has ever been developed so quickly, never mind manufactured for the world. Researchers' success or failure could determine whether the virus becomes endemic, recurring in countries around the world year after year, or is ultimately checked.  With the health of their citizens at stake, governments are investing enormous sums of money into vaccine research and development, and to prepare for manufacturing and distributing what will likely need to be hundreds of millions of doses necessary to keep infection at bay.

Although none of the coronavirus vaccines under development has proved its efficacy yet in clinical trials, at least 5.7 billion doses have been pre-ordered  around the world. First shipments of a COVID-19 vaccine created by Western laboratories have often been snapped up by the United States. Five vaccines — three Western and two Chinese — are in Phase 3 efficacy trials involving thousands of people. In a surprise announcement, Russian President Vladimir Putin claimed Tuesday that a vaccine dubbed Sputnik V — after the Soviet satellite — conferred “sustainable immunity” against the novel coronavirus. As research laboratories around the world race to develop a vaccine, manufacturers have received financing to help them prepare to have millions of doses ready to administer in 2021 or even before the end of the year.

Oxford University, working with the Swedish-British pharmaceutical group AstraZeneca, hopes to have results by September, while the US biotech company Moderna, partnering with the U.S. National Institutes of Health (NIH), is aiming for the end of the year, possibly November. U.S. President Donald Trump has launched “Operation Warp Speed” in a bid to develop, manufacture and distribute a COVID-19 vaccine to all Americans by January 2021. Hundreds of millions of dollars have been directed to vaccine developers, including nearly $500 million to Johnson & Johnson at the end of March. The United States has allocated funding to more companies than any other nation in the hope that one of them will come up with the vaccine to counter the highly contagious virus. So far, Washington has handed out at a total of at least $9.4 billion to seven vaccine developers and signed manufacturing contracts with five of them to provide 700 million doses. The companies involved are: Johnson & Johnson, Moderna, Oxford/AztraZeneca, Novavax, Pfizer/BioNTech, Sanofi/GSK, Merck Sharp and Dohme.  Two vaccine developers — Oxford/AztraZeneca and Sanofi/GSK — have signed or are in advanced negotiations with the European Commission to provide a combined 700 million vaccine doses. Britain, because of Brexit, is negotiating a separate pre-order of 250 million doses from four developers.  Japan is counting on 490 million doses from three suppliers, including 250 million from Novavax of the United States. Pharmaceutical giant Takeda bought the rights to a Novavax vaccine for Japan, which has funded the research. It would be produced locally.

Brazil chose a similar model, ordering 100 million doses from AstraZeneca and partnering with China’s Sinovac to produce 120 millions of CoronaVac, which is already undergoing testing with Brazilians. Clinical tests of two Chinese vaccine candidates — Sinovac and Sinopharm — are well underway but only a few international partnerships have been announced, the one with Brazil and a possible one with Indonesia. Russia said 20 nations have pre-ordered 1 billion doses of Sputnik V and that with foreign partners it would be able to produce 500 million doses a year in five countries. The Coalition for Epidemic Preparedness Innovations, launched in 2017 by Norway, India, the Bill and Melinda Gates Foundation and the Wellcome Trust, seeks to ensure that there is “equitable access” to future vaccines. It has pre-ordered 300 million doses from AstraZeneca for dozens of developing countries in a partnership with The Vaccine Alliance. Billions of doses would be produced for Asia and elsewhere by the giant Serum Institute of India (SII), the largest vaccine producer in the world. Novavax and AstraZeneca have separately signed agreements with SII to produce a billion doses each for India and low- and middle-income countries on the condition that they prove their efficacy in clinical trials.