On Dec. 7, 2020, an universal influenza virus vaccine, which produces antibodies that target the part of the surface protein of the influenza virus known to neutralize diverse influenza strains, was described in a study published in the journal Nature Medicine. This chimeric hemagglutinin (HA)-based vaccine has the potential to provide long-lived protection with two or three immunizations, eliminating the need for revaccination.

Seasonal influenza is a major public health concern, triggering as many as 650,000 deaths every year globally, according to the World Health Organization. In addition, influenza pandemics, similar to the current COVID-19 outbreak, occur at irregular intervals and can claim millions of lives. The most devastating example is the H1N1 pandemic of 1918, which caused approximately 40 million deaths.

Influenza virus vaccines — the best preventive weapon in the public health arsenal against seasonal influenza — contain three or four strains of the influenza virus that respond to the viruses circulating in the human population. Their inherent weakness, however, is that vaccine strains in the annual formulations are based on global health surveillance and predictions that are often out of sync with the strains that actually circulate. The situation is compounded in the case of emerging pandemic viruses, since these outbreaks cannot be predicted and emerge suddenly, requiring newly matched vaccines to be generated. This process requires at least six months, leaving large portions of the population vulnerable.

The chimeric HA vaccine seeks to correct this uncertainty by targeting a different part of the hemagglutinin protein, the major surface glycoprotein of the influenza virus that binds to host cell receptors.

Conventional vaccines induce neutralizing antibodies that target the distal part of the hemagglutinin, known as the globular head domain. “Unfortunately, the virus is able to escape neutralization by mutating this part of hemagglutinin through a process known as antigenic drift,” explains Peter Palese, PhD, Professor of Microbiology and Chair of the Department of Microbiology at Icahn School of Medicine at Mount Sinai, and co-author of the study. “This genetic change, or shift, in the virus results in immunity to only specific strains of the influenza virus, requiring frequent re-formulation and re-administration of seasonal vaccines. Our chimeric HA vaccine, by contrast, is directed at the proximal part of the HA protein — the stalk domain — which has been shown to broadly neutralize diverse influenza virus strains in both animal models and humans.”