Researchers make a huge step towards a universal flu vaccine
Friday, October 25, 2019
The influenza virus is a scourge that causes millions of illnesses and thousands of deaths in the United States and across the globe each year. Between 37.4 million and 42.9 million people in the nation experienced flu illnesses from Oct. 1, 2018, through May 4, 2019, according to estimates by the Centers for Disease Control and Prevention (CDC), resulting in as many as 647,000 hospitalizations and 61,200 deaths.
Flu vaccination reduces the risk of influenza illness by as much as 40 to 60% in the general population when the current flu vaccine is a good match for the influenza virus strains circulating at the time.
Researchers around the world are feverishly working to develop a universal flu vaccine that would cover all influenza strains. They may now be a step closer to creating such a vaccine, thanks to researchers at the Icahn School of Medicine at Mount Sinai, who collaborated with the international nonprofit PATH, the Cincinnati Children’s Hospital Medical Center, the University of Chicago, and the Duke Early Phase Clinical Research Unit.
The team of researchers focused their attention on hemagglutinin, which is a protein present on the surface of flu viruses. Hemagglutinin directs flu viruses to the host cell, which they then infect.
Hemagglutinin has two main components: the head and the stalk. Most vaccines target the head, which differs from strain to strain. This newest study builds on others that show using the variant protein, chimeric hemagglutinin (cHA), to target the stalk may be the key to developing a universal flu vaccine.
In short, they found that single vaccination with an adjuvanted chimeric haemagglutinin-base successfully activated antibodies and induced a broad antibody response, not only to human influenza viruses currently circulating, but also to bat and avian influenza virus subtypes.
The team tested a number of cHA-based vaccination regimens to see if they could induce the antibodies necessary to provide broad protection against flu virus infection. They published their results in The Lancet Infectious Diseases.
Research Paves the Way to a Universal Flu Vaccine
The team performed a randomized, observer-blinded study in 65 healthy adults in two medical centers in the U.S. In this planned interim analysis, the researchers used a blinded study group to assess the primary endpoints of reactogenicity and safety.
The researchers randomly assigned participants to one of three prime-boost, chimeric hemagglutinin-based vaccine regimens or to one of two placebo groups. One vaccine regimen included a chimeric H8/1, intranasal, live-attenuated vaccine in the first vaccine, followed by a non-adjuvanted, chimeric H5/1, intramuscular, inactivated vaccine (IIV) 85 days later.
The second vaccine regimen was the same as the first, except that the IIV was adjuvanted with AS03. The third vaccine regimen included an adjuvanted cH8/1 IIV prime with an adjuvanted cH5/1 IIV boost on day 85.
The team discovered that the IIV — but not the live attenuated vaccine — triggered a noteworthy antibody response after the first vaccination, with a significant boost in anti-H1 stalk titers. Specifically, they noted a seven-fold rise in anti-H1 stalk antibody titers on the 29th day. All three regimens induced measurable H1 stalk antibody responses following the boosts.
Participants tolerated the vaccine regimens well and no safety concerns arose.
This proof-of-principle study is the first to demonstrate that a rationally designed vaccine can induce anti-stalk titers in humans. The results may pave the way for the further development of universal influenza vaccines.
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