Prominent approaches to designing a universal influenza vaccine focus on a conserved region of the hemagglutinin (HA) virus surface protein, the HA stem.
Universal flu vaccine 2019
A recent article published by Bangaru et al. in Cell reported the discovery of a naturally occurring human antibody that can bind to a previously unknown site of vulnerability on the head of the HA protein. Because this newly discovered site is conserved across several influenza viral strains, similar to the HA stem, it has the potential to become an additional attractive target for universal influenza vaccine design.
The antibody that binds to this new site, FluA-20, was discovered in a patient who received annual influenza vaccinations for over two decades and previously participated in clinical trials for pandemic influenza vaccines. Blood samples for antibody isolation were taken after immunization with a current seasonal influenza vaccine. The isolated antibody showed strong binding affinity to HA proteins in different influenza virus strains in a region of the HA head that was only transiently accessible to antibody attack.
Antibody binding caused the HA molecule to fall apart, thus preventing viral entry into the cell. Since epitopes on HA proteins, especially on the head region, mutate rapidly due to antigenic drift, annual influenza immunization with updated strains is required. However, vaccine efficacy varies from year to year, with an average efficacy of just 45% over the past 10 US influenza seasons.
Universal influenza vaccines are designed to generate antibodies that recognise conserved epitopes on the influenza virus surface. They are supposed to protect against more than one virus strain, and consequently for more than one season, potentially eliminating the need for annual immunizations. The development of such vaccines is underway, with the most advanced candidates in Phase III being Biondvax’s M-001 and Medicago’s MT-2271, and a new entry is the National Institutes of Health’s (NIH’s) H1ssF_3928.
According to GlobalData’s proprietary Clinical Trials Databases, the seasonal influenza drug pipeline is highly active, with over 230 experimental products in all stages of development, most of them in the preclinical stage, and six Phase II candidates.
The 2018–2019 influenza season is wrapping up in the Northern hemisphere, and the Centers for Disease Control and Prevention (CDC) estimates that the US alone experienced around 40 million influenza cases, with 531,000–647,000 hospitalisations and 36,400–61,200 influenza-related deaths, indicating strong unmet needs for more effective vaccines and higher vaccination rates.
Although key opinion leaders (KOLs) interviewed by GlobalData remain sceptical about whether universal influenza vaccines will be commercially available within the next five years, this new antibody discovery is a promising approach to increase influenza vaccine efficacy.
NIH Joins the Race for a Universal Influenza Vaccine, April 2019
Universal Influenza Vaccine Development Takes Front Seat in WHO’s Influenza Strategy report, March 2019
GlobalData (2019). Seasonal Influenza Vaccines: Global Forecast and Market Analysis to 2028, to be published
GlobalData (2019). Respiratory Syncytial Virus (RSV): Opportunity Analysis and Forecasts to 2028, to be published