With the morbidity and mortality rates for this year’s influenza season beginning to mount there is some welcome news from investigators at the Institute for Biomedical Sciences at Georgia State University. The researchers developed and showed that a novel nanoparticle vaccine that combines two major influenza proteins is effective in providing broad, long-lasting protection against the influenza virus in mice, showing promise as a universal flu vaccine.
Findings from the new study—performed in mice and published recently in Advanced Healthcare Materials through an article titled “Double‐Layered M2e‐NA Protein Nanoparticle Immunization Induces Broad Cross‐Protection against Different Influenza Viruses in Mice”—suggest this unique vaccine combination has potential as a universal influenza vaccine or component of such vaccines.
The double-layered nanoparticle vaccine contains the influenza virus proteins matrix protein 2 ectodomain (M2e) and neuraminidase (NA). Mice were immunized with the nanoparticle vaccine before being exposed to the influenza virus, and they were protected against six different strains of the virus.
“This nanoparticle antigen combination conferred mice with strong cross-protection,” explained lead study investigator Ye Wang, a doctoral candidate at the Institute for Biomedical Sciences. “It can protect mice from different strains of influenza virus. Each season, we have different flu strains that affect us. By using this approach, we hope this nanoparticle vaccine can protect humans from different strains of the influenza virus.”
Influenza is a leading cause of death by infection. Seasonal flu vaccines are insufficient to prevent influenza outbreaks and developing a universal influenza vaccine is the ideal strategy for eliminating public health threats of influenza epidemics and pandemics. A universal influenza vaccine would eliminate the need for vaccinations each season and offers universal protection against all influenza strains.
The influenza virus protein M2e is found in all influenza virus strains, with each strain having a very similar version, and the protein has mutated very slowly over time. The protein NA is found on the surface of the influenza virus and has also mutated much slower than other influenza proteins. This double-layered nanoparticle vaccine uses M2e as its core, and NA is coated on the surface.
In the current study, mice were exposed to one of six influenza virus strains after receiving the nanoparticle vaccine by intramuscular injection. The vaccine proved to have long-lasting immune protection, which was unchanged against viral challenges up to four months after immunizations.
“Immunizations with these protein nanoparticles induce immune protection against different viruses of homologous and heterosubtypic NA in mice,” the authors wrote. “Double‐layered M2e‐NA protein nanoparticles induce higher levels of humoral and cellular responses compared with their comprising protein mixture or M2e nanoparticles. Strong cytotoxic T cell responses are induced in the layered M2e‐NA protein nanoparticle groups. Antibody responses contribute to the heterosubtypic NA immune protection. The protective immunity is long-lasting.”
“It’s important to mention that a lot of flu vaccines haven’t focused on NA before,” noted study co-author Gilbert Gonzalez, a scientist at the Institute for Biomedical Sciences. “NA is becoming a more important antigen for influenza vaccine research. Previously, it had been ignored or discounted because hemagglutinin (HA) is much more dominant. When you get a flu infection, your body reacts to the HA.”
The research team is now looking toward the future and plan to load this double-layered nanoparticle vaccine onto microneedle patches for skin vaccination.
“These results demonstrate that double‐layered protein nanoparticles containing structure‐stabilized M2e and NA can be developed into a universal influenza vaccine or a synergistic component of such vaccines,” the authors concluded. “Layered protein nanoparticles can be a general vaccine platform for different pathogens.