Influenza: A Universal Flu Vaccine Successfully Completes Phase I Trial

Scientists have been trying for years to develop a universal flu vaccine that does not need to be renewed every year. They may be on the right track because, for the first time, there is a Phase I trial with promising results.

Flu Shot

The Seasonal Flu

The seasonal flu vaccine consists of the dominant strains of the influenza A subtypes H1 and H3 and the dominant strain of the circulating influenza B virus (so it is a trivalent vaccine consisting of 3 types of strains). Once the composition of the vaccine according to the circulating strains is determined, the pharmaceutical industry has about 6 months to produce it and make it available every year in September/early October. However, sometimes the vaccine overlooks the circulating strain completely and is therefore only partially effective. In addition, annual repeat vaccination is very expensive.

A Universal Vaccine

A vaccine that triggers an immune response against a variety of flu virus strains and subtypes has produced strong and lasting results in early human clinical trials, according to a study published Dec. 7 in the journal Nature Medicine.

The current flu vaccine targets an antigen called hemagglutinin (HA), which is found on the surface of the virus and is frequently mutated. Therefore, the vaccine must be reformulated every year based on the strains that circulate in the different regions.

For more than 20 years, scientists have been trying to develop a universal flu vaccine that could escape HA mutations. For example, some have tried to develop vaccines that target the virus’s internal proteins, such as the M or NS proteins or neuraminidase (NA). These approaches have proven ineffective so far.

Chimeric Hemagglutinin

For their universal vaccine project, the Mount Sinai researchers who initiated the study continued to focus on hemagglutinin. But while the seasonal vaccine targets the distal part of the glycoprotein, known as the globular head, “the vaccine targets the proximal part of the HA protein–stalk domain–which has been shown to broadly neutralize different strains of the influenza virus in animal models and in humans,” says Peter Palese, chairman of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai and co-author of the study. Strain-specific antibodies can neutralize multiple types of strains.

The problem is that HA head immunodominance makes it difficult to induce a strong anti-stem-dominant antibody response. Therefore, to redirect the immune response from the head to the stalk domain, researchers have created “chimeric” HA by combining the stalk domains and the globular heads. In 2015, the researchers tested this approach with nanoparticles and an adjuvant that reduces the density of hemagglutinin on the surface of the virus so that antibodies can find the stalk domain more easily.

Protection for at least 18 months

The Phase I clinical trial, funded in part by the Bill & Melinda Gates Foundation, evaluated the safety and immunogenicity of the vaccine in 65 participants in the United States and found a strong immune response that lasted at least 18 months after vaccination. Several other phase 1 trials of the universal virus are underway, but this is the first to be published.

While these results are encouraging, they say nothing about the vaccine’s effectiveness in an epidemic, which is the task of Phase II and III trials. The Phase I trial is limited to demonstrating that the vaccine is safe and provokes an immune response. More clinical trials in larger populations are needed to get a clear picture of the future of the vaccine.