Can A Universal Influenza Vaccine End Seasonal Flu Forever?

Ongoing research at the Cleveland Clinic is developing a vaccine for influenza that could end our annual scramble to predict and develop protection against the latest new flu strains that endanger lives.

The World Health Organization (WHO) has estimated that seasonal influenza infects a billion every year. Between 3 and 5 million of us develop severe symptoms and between 290,000 and 650,000 die every year. Of those deaths, 99% happen in children under the age of 5 and largely located in Developing World countries.

The United States sees between 12,000 and 52,000 annual deaths from the flu. Canada sees 3,500 deaths annually. The variance in these annual numbers is related to the seasonal severity of new strains and other conditions that make people more susceptible.

Current annual flu shots reduce the risk of death. A May 2023 published meta-analysis study calculates reduced risk of death from flu vaccines at 18%, and at 29% for hospitalizations from resulting complications. In last year’s flu season, estimates indicated that the annual vaccine prevented 3,700 deaths in the U.S. and was 41 to 44% effective in preventing hospitalizations.

What if a flu vaccine could protect us beyond one year from all influenza strains, those in the present and future? That’s where work at the Cleveland Clinic’s Lerner Research Institute may yield a universal vaccine candidate. Currently in mice studies, such a vaccine is showing promise. Described as the “next-generation influenza virus vaccines” in a study published on August 22, 2024, in the Journal of Virology, a vaccine with this capability would protect us against all strains that infect humans.

Why do we need a universal influenza vaccine? States Michael Carlock, Program Manager in the laboratory working on influenza vaccine development, “Seasonal influenza vaccines are mostly effective against pathogens with antigens matching the vaccine formulation. Viruses like to mutate constantly. If their antigens change too much, our immune system won’t recognize them as the pathogen that the vaccine trained them to fight. We constantly need to update our vaccines to keep up with these new variants and mutations.”

Why we guess wrong sometimes in developing seasonal flu vaccines has to do with the rapid changes happening in these viruses. A strain can mutate into multiple variants and multiple strains can emerge simultaneously. Only through rigorous statistical analysis can we try to predict and place bets on which strains will likely circulate in the coming flu season. Then we begin production while in the interim new strains may emerge to become dominant and prove we got it wrong. If this sounds familiar, it is the same horserace we have witnessed with COVID-19 as it has evolved through multiple generations making it necessary to rearm and keep that virus at bay.

The technology behind the new Cleveland Clinic vaccine is called COBRA which stands for Computationally Optimized Broadly Reactive Antigens. COBRA uses public databases to study thousands of genetic sequences of influenza strains spanning several years. The sequences are then analyzed and dissected down to proteins and their amino acid building blocks.

COBRA has been used in helping to identify new COVID-19 strains as well as HIV, RSV and several insect-borne viruses. To produce the multi-variant, multi-season vaccine, COBRA identified eight proteins that triggered sustained immune responses, referred to as “a greatest hits album” by Naoko Uno, a virologist and project leader. The proteins identified are associated with H1, H2, H3, H5 and H5N1 (avian influenza or bird flu) and H7 influenza strains.

The octavalent (standing for eight) intranasal vaccine has produced antibodies to combat the virus within 4 weeks after being administered. This vaccine could prove to be particularly important as bird flu finds its way to us. Many virologists have identified H5N1 as the likely next global human pandemic. It has proven to be endemic in poultry in Asia with sudden death with no prior signs of infection occurring as high as 90 to 100% within 48 hours. In wild bird populations, H5N1 has caused massive die-offs although some species appear asymptomatic. Human exposure is on the increase and mortality rates in cases have been 50%, far higher than any seasonal influenza.

Human clinical trials of this next-generation flu vaccine are expected within one to three years. Sooner than later would be nice.