Results indicate wide cross-protection against influenza A subtypes and strains in a young and aged mouse model.
Sang-Moo Kang, PhD, of the Center for Inflammation, Immunity, and Infection at the Institute for Biomedical Sciences at Georgia State University in Atlanta and colleagues conducted the study. Results showed that a vaccine can be developed against different strains of influenza A, as well as different subtypes through genetic engineering.
Flu vaccines often have low efficacy because the influenza virus is always changing. Previous vaccine efficacy hovered around 33% against influenza A subtype H3N2 over the past 10 years; during the 2014-2015 flu season vaccine efficacy was as low as 6%, according to a press release from Georgia State University.1 The emergence of H3N2 variants containing new mutations that confer higher virulence, and an outbreak of influenza A subtype H7N9 showing pandemic potential offer 2 examples of why the development of effective, universal flu vaccines is essential to protect public health.1
Researchers explained that there are specific obstacles with the H3N2 influenza A viruses due to mutations of the stalk in strains that circulate and stalk proteins have unstable structures.1 “These drawbacks have been difficult to overcome in developing effective H3 stalk-based vaccines,” the release noted.1
The new universal vaccine was developed by genetically linking the stalk protein found in flu A H3N2 virus strains and the extracellular domain of matrix 2 (M2e): 2 parts of the virus that have remained mostly unchanged over time.1
“The M2e-stalk protein, for the first time, could be easily produced in bacterial cell cultures at high yields and was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2 and H7N9) at similar levels in adult and aged mice,” Kang said in the release.1 “These results provide evidence that M2e-stalk genetic fusion proteins can be produced in a large scale at low cost and developed as a universal influenza A virus vaccine candidate for young and aged populations,” he added.
In a brief interview with Drug Topics®, Kang said the most significant takeaway from the study was that “this vaccine candidate product is thermostable, easily scaled up with high yield, and thus will be available for low-income, low-resource countries.” He explained that the new, universal influenza vaccine “inducing dual arms (M2e + stalk proteins) of immunity can provide a broader range of cross-protection against influenza A viruses, including seasonal and pandemic potential bird flu as evidenced in this report from preclinical mouse animal studies.” Kang emphasized that the next steps in the research involve advanced preclinical studies in more relevant ferret animal models in hopes of preparing the vaccine for human trials.
The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) funded the study.
Many attempts at a universal flu vaccine are in progress. The Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota in Minneapolis reports 143 vaccine candidates in progress, with 27 in clinical trials on their Universal Influenza Vaccine Technology Landscape Database.3
References
1. New universal flu vaccine offers broad protection against influenza A virus infections, researchers find. News release. Georgia State University. June 30, 2022. Accessed July 20, 2022. https://news.gsu.edu/2022/06/30/new-universal-flu-vaccine-offers-broad-protection-against-influenza-a-virus-infections-biomedical-sciences-researchers-find/
2. Subbiah J, Oh J, Kim KH, et al. A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine. NPJ Vaccines. 2022;7(1):68. Published 2022 Jun 29. doi:10.1038/s41541-022-00498-6
3. Universal influenza vaccine technology landscape database. Center for Infectious Disease Research and Policy. Accessed July 24, 2022. https://ivr.cidrap.umn.edu/universal-influenza-vaccine-technology-landscape