Virus World

The vaccine provided protection from Ebola virus, Sudan virus, Marburg virus and Lassa virus. Scientists funded by the National Institutes of Health have developed an investigational vaccine that protected cynomolgus macaques against four types of hemorrhagic fever viruses endemic to overlapping regions in Africa. The University of Texas Medical Branch in Galveston and Profectus BioSciences of New York are developing and testing the candidate quadrivalent VesiculoVax vaccine, with support from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Redeemer’s University in Nigeria.

The newly published study in the Journal of Clinical Investigation describes how the vaccine was created using a live-attenuated (weakened) vesicular stomatitis virus to deliver proteins that elicit protective immune responses. The proteins are from Ebola virus (Kikwit strain), Sudan virus (Boniface strain, which also causes Ebola virus disease), Marburg virus (Angola strain) and Lassa virus (Josiah strain). There are no licensed vaccines to provide protection from any of those viruses — all of which can cause severe disease and death — although the European Medicines Agency has recommended licensing a VSV-Ebola vaccine. Importantly, the monkeys infected in the study were exposed to different strains of Sudan virus (Gulu) and Lassa virus (0043/LV/14) than those in the candidate vaccine to help the researchers determine whether the vaccine would be cross-protective. Lassa 0043/LV/14 is circulating in an outbreak in Nigeria that began in 2018. Previous studies indicate that the investigational Ebola virus (Kikwit) vaccine will protect against other strains of Ebola virus.

The scientists inoculated 20 macaques with a primary and booster dose of quadrivalent VesiculoVax. The animals had five blood draws to check for an immune response, including on the day of initial vaccination and on days 10 and 28, then on day 56 when they received a booster inoculation, and again on day 66. On day 84 scientists infected the macaques with the four different hemorrhagic fever viruses and monitored them to day 112. Twelve additional macaques in the study who were infected with the four viruses but not vaccinated all became sick, but none of the vaccinated animals did. Only one of the 20 vaccinated animals had any of the four hemorrhagic fever viruses detectible (Lassa) following the study. The scientists state that the addition of the Lassa virus component to their multivalent vaccine is an exciting research advance as they already had developed an investigational trivalent vaccine that provided protection against Ebola, Sudan and Marburg viruses. The researchers now plan further vaccine tests against other strains of Lassa virus, and they want to further evaluate whether a single-dose quadrivalent vaccine appears safe and effective.

Published in the Journal of Clinical Investigation (October 22, 2019):

https://doi.org/10.1172/JCI131958

Takeda has laid out considerable time, effort and money on its dengue vaccine program despite Sanofi's trouble with its earlier entrant. Now, the Japanese drugmaker is touting phase 3 data showing the vaccine was 80% effective at preventing dengue.

In a study called Tides, investigators tested the Takeda vaccine, TAK-003, against placebo in more than 20,000 participants aged four to 16 in dengue-endemic countries in Latin America and Asia. Twice as many participants received the vaccine as those who received placebo. In those who received both doses, the vaccine was 80.2% effective, the team reported Wednesday. Investigators tracked 61 cases of dengue in the vaccine group versus 149 in the placebo group, according to results published in The New England Journal of Medicine. 

Importantly, efficacy varied among dengue serotypes. The vaccine was 73.7% effective against dengue serotype 1, 97.7% effective against serotype 2 and 62.6% effective against serotype 3. The investigators didn't track enough serotype 4 cases to reach an efficacy determination. The shot was 95.4% effective in preventing dengue that required hospitalization; there were five hospitalizations in the vaccine group versus 53 in the placebo group. The company has said it expects phase 3 studies to form the basis for regulatory submissions. Derek Wallace, Takeda’s dengue vaccine program chief, told FiercePharma the company is “encouraged by the data” as the results demonstrate the vaccine “has a potential to have a very big impact” on the dengue burden worldwide.

Takeda is particularly pleased about the vaccine’s performance in participants who hadn't had a prior dengue infection, Wallace said. In that group, the vaccine was 74.9% effective in preventing dengue. Pharma watchers may remember that Sanofi's dengue vaccine, the world's first, tripped up because of safety problems in those who hadn't had prior infections. The French drugmaker rolled out the shot in 2016, but in late 2017, the company said a new analysis had found it could cause more serious disease in those who’d been infected before. The disclosure triggered outrage in the Philippines, where officials had started a vaccination campaign. All told, the scandal knocked Sanofi’s vaccine off its launch trajectory and the company faced numerous questions about the vaccine's safety and its rollout in the Philippines. Dengvaxia originally had blockbuster expectations, but in 2018, its sales weren’t significant enough for Sanofi to disclose. Still, Takeda isn't backing down from the dengue vaccine challenge. The company just this week opened a €130 million plant in Germany to meet global demand for the shot once it launches. The drugmaker plans to employ up to 200 workers at the plant. 

Clinical Study published in New England Journal of Medicine (November 6, 2019):

https://doi.org/10.1056/NEJMoa1903869