Mount Sinai scientists, from left, Peter Palese, PhD; Florian Krammer, PhD, with a 3D model of the influenza virus hemagglutinin; and Adolfo García-Sastre, PhD.
The quest to develop a universal influenza vaccine that would be administered only once or twice in an individual’s lifetime and cover every strain of the virus moved closer to becoming a reality in October, when researchers at the Icahn School of Medicine at Mount Sinai showed that a novel method of protection against the influenza virus was safe and induced strong immune responses in humans.
The interim results of this phase 1 clinical trial—led by Mount Sinai scientists Florian Krammer, PhD; Peter Palese, PhD; and Adolfo García-Sastre, PhD—were published online in the October 17, 2019, issue of The Lancet Infectious Diseases.
Two types of proteins, hemagglutinin and neuraminidase, cover the surface of the influenza virus. Current influenza vaccines target the head of the hemagglutinin—a structure that changes often. Mount Sinai’s strategy, known as chimeric hemagglutinin (cHA), targets the stalk of the hemagglutinin, which is less variable.
In the Lancet Infectious Diseases study, the research team tested several cHA vaccine regimens in combination with an adjuvant, an ingredient that boosts the immune response to vaccines. All of the regimens induced antibody responses. But, “one vaccine regimen induced a broad antibody response after the first dose, and this response was not only cross-reactive for the currently circulating influenza virus but also to avian (bird) and bat influenza subtypes,” according to Dr. Krammer, Mount Sinai Professor of Vaccinology and Professor of Microbiology at the Icahn School of Medicine at Mount Sinai.
This, he says, showed that one vaccination might be enough to induce protection against changing seasonal influenza viruses and pandemic influenza viruses yet to arise. “The results indicate that we are moving toward a universal influenza vaccine, but these are still interim results.”
Dr. Palese, Horace W. Goldsmith Professor of Medicine, and Professor and Chair of the Department of Microbiology at the Icahn School of Medicine at Mount Sinai, says the “ideal vaccine, given only once in a lifetime and protective against all influenza virus strains,” would go a long way in improving the health of millions of people in the United States and around the world.
A universal vaccine would overcome “antigenic drift,” the small changes in the genes of influenza viruses that render viruses different from one another and allow them to escape human immunity. This is the primary reason why influenza vaccines vary in effectiveness from one season to another and must be updated every year.
Still, influenza vaccines do offer protection from severe disease and physicians strongly recommend that patients get them annually. Despite their widespread availability, however, more than half of Americans were unvaccinated as of the beginning of December 2019, according to NORC at the University of Chicago, which conducts the National Immunization Survey for the U.S. Centers for Disease Control and Prevention (CDC).
Influenza remains deadly for some. The World Health Organization estimates that influenza-related respiratory illnesses account for between 290,000 and 650,000 deaths per year. Dr. Krammer says, “Developing new vaccines takes a lot of time and it’s hard to estimate how long it will take, but I firmly believe we will have a universal flu vaccine in our lifetime and probably sooner.”
In addition to Dr. García-Sastre, a co-senior researcher on the Lancet Infectious Diseases study, and the Irene and Dr. Arthur M. Fishberg Professor of Medicine, and Director of the Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, contributors included Cincinnati Children’s Hospital Medical Center; Duke University School of Medicine; the University of Chicago; and the nonprofit international health organization PATH. Funding was provided by a grant from the Bill & Melinda Gates Foundation.