The future of haemagglutinin stalk-based universal influenza vaccines

The development of next-generation influenza vaccines with increased breadth and duration of protection is among one of the objectives in WHO's Global Influenza Strategy for 2019–2030, which calls for the development of improved global tools by 2030 to benefit all countries and to instil public confidence and vaccine uptake. 1 Moore KA Ostrowsky JT Kraigsley AM et al. A research and development (R&D) roadmap for influenza vaccines: looking toward the future. Vaccine. 2021; 39: 6573-6584 Crossref PubMed Scopus (7) Google Scholar Over the past two decades, more than 100 universal influenza vaccine prototypes have been proposed; however, only few have progressed beyond animal studies, and even fewer results have been made publicly available. 2 Isakova-Sivak I Stepanova E Mezhenskaya D et al. Influenza vaccine: progress in a vaccine that elicits a broad immune response. Expert Rev Vaccines. 2021; 20: 1097-1112 Crossref PubMed Scopus (4) Google Scholar In this regard, the publication of the results of a clinical trial of influenza vaccines based on chimeric (c) haemagglutinins was highly anticipated. 3 Folschweiller N Vanden Abeele C Chu L et al. Safety and immunogenicity of chimeric haemagglutinin influenza split-virion vaccines, adjuvanted with AS01 or AS03 or non-adjuvanted: a phase 1–2 randomised controlled trial. Lancet Infect Dis. 2022; (published online April 21.)https://doi.org/10.1016/S1473-3099(22)00024-X Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar In The Lancet Infectious Diseases, Nicolas Folschweiller and colleagues 3 Folschweiller N Vanden Abeele C Chu L et al. Safety and immunogenicity of chimeric haemagglutinin influenza split-virion vaccines, adjuvanted with AS01 or AS03 or non-adjuvanted: a phase 1–2 randomised controlled trial. Lancet Infect Dis. 2022; (published online April 21.)https://doi.org/10.1016/S1473-3099(22)00024-X Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar report the results of a phase 1–2 randomised controlled trial assessing the reactogenicity, safety, and immunogenicity of inactivated influenza vaccines (split virion), which contained heterosubtypic H5, H8, and H11 heads and an identical H1 haemagglutinin stalk domain, as well as the immunostimulatory effects of two adjuvants, AS01 and AS03. Reactogenicity, safety, and immunogenicity of chimeric haemagglutinin influenza split-virion vaccines, adjuvanted with AS01 or AS03 or non-adjuvanted: a phase 1–2 randomised controlled trialThe stalk domain seems to be a rational target for development of a universal influenza virus vaccine via administration of chimeric haemagglutinins with head domains to which humans are naive. Full-Text PDF