Research Results Show Promise Toward Development of a Universal Influenza Vaccine

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A study published in Nature Communications shows a promising approach to developing a universal influenza vaccine with the intention of conferring lifetime immunity against an evolving virus after a single dose. According to the investigators, the “one and done” vaccine platform was tested against the virus that is believed to be the most likely to trigger the next pandemic.¹

“Should a deadly virus such as H5N1 infect a human and ignite a pandemic, we need to quickly validate and deploy a new vaccine,” said co-corresponding author Douglas Reed, PhD, associate professor of immunology at the University of Pittsburgh Center for Vaccine Research, in a news release.¹

For this study, the investigators wanted to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines that expressed conserved internal influenza antigens could protect against lethal influenza challenge. To measure this, the investigators administered Mauritian cynomolgus macaques (MCM)—nonhuman primates—with cynomolgus CMV (CyCMV) vaccines that express the H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. A total of 11 MCMs were included in the study, as well as a control group of unvaccinated primates who were exposed to the H5N1 virus.²

“The problem with influenza is that it’s not just 1 virus. Like the SARS-CoV-2 virus, it’s always evolving the next variant and we’re always left to chase where the virus was, not where it’s going to be,” explained senior author Jonah Sacha, PhD, professor and chief of the Division of Pathobiology at Oregon National Primate Research Center, Oregon Health and Science University, in the news release. “It worked because the interior protein of the virus was so well preserved. So much so, that even after almost 100 years of evolution, the virus can’t change those critically important parts of itself.”¹

The method, according to the investigators, involves administered small pieces of target pathogens into the common herpes virus CMV—which infects most people in their lifetimes—and typically produces mild to no symptoms in individuals. The virus acts as a vector that is designed to induce an immune response from the body’s own T cells. Additionally, the investigators note that this approach is different from common vaccines, including the flu vaccines, and are designed to induce an antibody response that targets the most recent evolution of the virus.^1,2

According to the findings, all 6 unvaccinated MCMs died within 7 days post-infection because of acute respiratory distress, whereas 6 of the MCMs (54.5%) vaccinated for CyCMV/Flu survived. The investigators note that the MCMs that survived appeared to present correlations with the magnitude of lung-resident CD4+ T cells specific to influenza prior to challenge. These data, according to the investigators, demonstrate that CD4+ T cells targeting preserved internal influenza proteins and can protect against highly pathogenic heterologous influenza.²

“It’s exciting because in most cases, this kind of basic science research advances the science very gradually; in 20 years, it might become something,” said Sacha in the news release. “This could actually become a vaccine in 5 years or less. It’s a very viable approach. For viruses of pandemic potential, it’s critical to have something like this. We set out to test influenza, but we don’t know what’s going to come next.”¹

The study suggests that CMV vaccines have the potential of generating effective and long-lasting immune responses against a wide variety of variants. Further, the promising findings support the need for additional research that explores effector memory T cell-based vaccines that can be used for the development of a universal influenza vaccine.^1,2

“I think it means within 5 to 10 years, a one-and-done shot for influenza is realistic,” Sacha said. “It’s a massive sea change within our lifetimes. There is no question we are on the cusp of the next generation of how we address infectious disease.”¹

References

1. Oregon Health & Science University. Study shows promise for a universal influenza vaccine. News release. July 19, 2024. Accessed July 22, 2024. https://www.eurekalert.org/news-releases/1051761

2. Malouli, D, Tiwary, M, Gilbride, RM, et al. Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge. Nat Commun 15, 6007 (2024) doi:10.1038/s41467-024-50345-6