Virus World

Remdesivir sped recovery of patients by several days, although it’s “not a home run. A candidate treatment for COVID-19 has shown convincing—albeit modest—benefit for the first time in a large, carefully controlled clinical trial in hospitalized patients. The infected people who received remdesivir, an experimental drug made by Gilead Sciences that cripples an enzyme several viruses use to copy their RNA, recovered in an average of 11 days versus 15 in patients who received a placebo. “Although a 31% improvement doesn’t seem like a knockout, 100% [success], it is a very important proof of concept,” said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), during an Oval Office meeting in which President Donald Trump was asked by media about a statement Gilead had released on the results. The patients treated with remdesivir also had a lower mortality rate—8% versus 11.6% in the group given the placebo—but this positive trend did not reach statistical significance, Fauci noted. (The full results from the trial have not been made public in a preprint or peer-reviewed paper.)

NIAID sponsored the study, which began on 21 February and enrolled 1063 patients at 68 sites in the United States, Europe, and Asia. A board that monitors safety and data from the trial informed investigators on 27 April that remdesivir was better than the placebo. Fauci says the board is releasing the overall results early in part on ethical grounds: Given the positive data, remdesivir must now be offered to all study participants, and trials of other treatments now underway must start to offer the drug instead of a placebo, Fauci said. The search for COVID-19 treatments that can do better than remdesivir remains a top priority. “It’s a promising signal, but we do not need to get hyperexcited—this is not a home run,” says Carlos del Rio, an infectious disease clinician at Emory University, one of the larger sites that participated in the remdesivir trial. In essence, he says, the study showed that patients who received the drug, which is given intravenously, could stop receiving supplemental oxygen earlier. Del Rio, a veteran of HIV drug development, which gradually advanced from nothing to effective treatments, hopes the results mark a first step for COVID-19. But he does not expect remdesivir will significantly ease the demands that COVID-19 is putting on hospitals, or brighten prospects for lifting shelter-in-place orders...

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has initiated the Collaborative Influenza Vaccine Innovation Centers (CIVICs) program, a new network of research centers that will work together in a coordinated, multidisciplinary effort to develop more durable, broadly protective and longer-lasting influenza vaccines. NIAID will provide up to approximately $51 million in total first-year funding for the program, which is designed to support the CIVICs program centers over seven years.

“To more effectively fight influenza on a global scale, we need better influenza vaccines that are more broadly protective,” said NIAID Director Anthony S. Fauci, M.D. “With the CIVICs program we hope to encourage an exchange of ideas, technology and scientific results across multiple institutions to facilitate a more efficient and coordinated approach to novel influenza vaccine development.” Seasonal influenza causes hundreds of thousands of hospitalizations and tens of thousands of deaths in the United States each year, according to the Centers for Disease Control and Prevention. While current seasonal influenza vaccines are widely available and provide important public health benefit, they could be improved. Notably, they do not always protect against all strains of circulating influenza viruses. Each year, months ahead of the flu season, scientists must make their best prediction as to which circulating viruses will be dominant. New seasonal influenza vaccines must be manufactured, distributed and administered to keep up with constantly evolving influenza viruses. This process can be slow, and if a drifted seasonal influenza virus emerges, that can impact the effectiveness of the vaccine against that virus. The relatively long timeline for vaccine production and the rapidly changing nature of influenza viruses poses a unique and difficult public health challenge for these reasons.

The CIVICs network will develop so-called universal influenza vaccines, which could provide longer-lasting protection than current vaccines and against a wider variety of influenza viruses. The CIVICs centers will conduct multidisciplinary research that supports the development of vaccine candidates through testing in preclinical studies, clinical trials and human challenge studies. The CIVICs network also will explore approaches to improve seasonal influenza vaccines, such as by testing alternative vaccine platforms or incorporating new adjuvants (substances added to vaccines to boost immunity). These advances could substantially reduce influenza hospitalizations and deaths in the future.

The CIVICs program will include three Vaccine Centers, one Vaccine Manufacturing and Toxicology Core, two Clinical Cores, and one Statistical, Data Management, and Coordination Center (SDMCC).

The Vaccine Centers will focus on designing novel vaccine candidates and delivery platforms with an emphasis on cross-protective vaccine strategies that could be used in healthy adults as well as populations at high risk for the most serious outcomes of influenza, such as children, older adults, and pregnant women. The Vaccine Centers also will focus on new ways to study influenza viruses and the human immune response to them through computer modeling, animal models and human challenge trials. The most promising candidate vaccines will advance to clinical trials conducted by the Clinical Cores. Vaccine candidates will first be evaluated for safety and immunogenicity in small Phase 1 clinical trials conducted among healthy adult participants. Successful vaccine candidates may eventually be advanced to larger Phase 2 clinical trials in healthy adults, or in specific age groups or at-risk populations. The Vaccine Manufacturing and Toxicology Core will work with the Vaccine Centers to develop and manufacture the vaccine candidates for clinical testing.....

One of the nation's top health experts recommends continuing avoiding large crowds and social interactions as the best defense against the pandemic.

A novel experimental vaccine against respiratory syncytial virus (RSV), a leading cause of severe respiratory illness in the very young and the old, has shown early promise in a Phase 1 clinical trial. The candidate, DS-Cav1, was engineered and developed by researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, who were guided by their atomic-level understanding of the shape of an RSV protein. An interim analysis of study data showed that one dose of the investigational vaccine prompted large increases in RSV-neutralizing antibodies that were sustained for several months. 

First described in 1956 as a cause of infant pneumonia, the health burden of RSV has long been underappreciated. In fact, the virus is an important contributor to serious illness worldwide and causes as many as 118,000 deaths annually among young children. In the United States each year, RSV infections account for approximately 57,000 hospitalizations and 2 million outpatient clinic visits among children younger than five years old, according to the Centers for Disease Control and Prevention. 

“A vaccine to prevent RSV is a long-sought goal that has eluded us for decades,” said NIAID Director Anthony S. Fauci, M.D. “The early results of this trial suggest that this structure-based strategy for developing an RSV vaccine may bring that goal within reach.”  After four weeks, levels of RSV-neutralizing antibodies in those who received 50 µg of vaccine (with or without alum) had increased sevenfold over the levels present prior to vaccination. A single dose of 150 µg without alum boosted neutralizing antibody levels 12-fold, while alum-adjuvanted vaccine at that dose prompted a 15-fold surge in neutralizing antibodies. The vaccine-induced antibody levels greatly exceed those seen following natural RSV infection in human challenge trials (where healthy volunteers are exposed to pathogens under carefully controlled conditions in order to observe the course of infection), when neutralizing antibody levels merely triple over those present before infection.

Original findings were published in Science on 02 August 2019:

https://doi.org/10.1126/science.aav9033