Universal Flu Vaccine Targets the Stalk Portion of the Protein

Mount Sinai universal influenza vaccine candidate using chimeric hemagglutinin approach
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A team led by researchers at the Icahn School of Medicine at Mount Sinai is getting closer to a universal flu vaccine using a novel approach they've developed called chimeric hemagglutinin (cHA).

In an October 17, 2019, press release, Icahn School of Medicine researchers, led by Peter Palese, Ph.D., Professor and Chair of Microbiology and Florian Krammer, Ph.D., Professor, said they ‘have focused their efforts on developing a ‘vaccine against the stalk portion of this protein.’

These researchers explained ‘a protein on the surface of influenza viruses, hemagglutinin, shepherds the virus into host cells. Hemagglutinin is comprised of a 'head' (variable) and a 'stalk' (varies less from strain to strain).’

Their study involved testing of several cHA-based vaccination regimens to see if they would induce antibodies that provide broad protection against influenza virus infections. 

The vaccine regimens examined in this study included:

  • a group receiving a chimeric H8/1 hemagglutinin-based live attenuated vaccine followed by a boost with a non-adjuvanted chimeric H5/1 hemagglutinin-based inactivated vaccine (IIV), and,
  • the same regimen but with the IIV having an adjuvant called AS03, and,
  • a prime-boost regimen including an adjuvanted cH8/1 IIV prime followed by an adjuvanted cH5/1 IIV boost.

The researchers found that the IIV, but not the live attenuated vaccine, induced a significant antibody response after the prime, with a strong increase in anti-H1 stalk titers. 

And all vaccine regimens induced detectable H1 stalk antibody responses after receiving boosts. An adjuvant, an ingredient that boosts the effectiveness of vaccines, was also part of the testing process.

"The vaccine induced a broad antibody response which was not only cross-reactive for currently circulating human influenza virus, but also to avian and bat influenza virus subtypes," said Dr. Florian Krammer, in the press release.

"It was surprising to find that the inactivated formulation with adjuvant-induced a very strong anti-stalk response already after the prime suggesting that one vaccination might be enough to induce protection against pandemic influenza viruses yet to arise.”

“The results indicate that we are moving towards a universal influenza virus vaccine, but these are still interim results. Additional results will be available upon completion of the study at the end of 2019."

This study is good news since the current flu vaccines provide protection only against the influenza strains they have been matched to, so a ‘universal’ flu vaccine that provides broader protection against most influenza viruses has been a long-standing dream.

In a study published in Nature in September 2019, Barney Graham, deputy director of the Vaccine Research Center at the US National Institute of Allergy and Infectious Diseases (NIAID), said: “The problem is that flu vaccines deliver inconsistent performance.”

“In a good season, we’re up to 60% effectiveness, but in bad, mismatched years it can be as low as 10% or 20%.”

The diverse Mount Sinai lead research team includes Adolfo García-Sastre, Ph.D., Professor of Microbiology and Director of the Global Health and Emerging Pathogens Institute at Icahn; Bruce Innis, M.D., Leader, Respiratory Infections and Maternal Immunizations at PATH; and Patrick Wilson, Ph.D., Professor of Medicine at the University of Chicago, have investigated whether several potential cHA-based vaccines might induce antibodies that would target the stalk of group 1 hemagglutinin-expressing influenza viruses.

The University of Chicago performed crucial testing; funding was provided by a grant from the Bill & Melinda Gates Foundation. And GlaxoSmithKline contributed some of the vaccines and adjuvants. Foundational support was provided by the National Institute of Allergy and Infectious Diseases.

The results were published in The Lancet Infectious Diseases.

Previously, on September 30, 2019, researchers at the Icahn School of Medicine at Mount Sinai received a contract award of up to $132 million from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), as part of a new Collaborative Influenza Vaccine Innovation Centers (CIVICs) program to further develop the universal flu vaccine.

The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region.

Influenza news published by Precision Vaccinations