We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expressed and purified from Escherichia coli was thermostable, displaying native-like antigenic epitopes recognized by antisera of different HA subtype proteins and influenza A virus infections. Adjuvanted M2e-H3 stalk vaccination induced M2e and stalk-specific IgG antibodies recognizing viral antigens on virus particles and on the infected cell surface, CD4+ and CD8+ T-cell responses, and antibody-dependent cytotoxic cell surrogate activity in mice. M2e-H3 stalk was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, H7N9) at similar levels in adult and aged mice. These results provide evidence that M2e-H3 stalk chimeric proteins can be developed as a universal influenza A virus vaccine candidate for young and aged populations.
Bibliographical noteFunding Information:
NIH/NIAID grants AI093772 (S.-M.K.), AI154656 (S.-M.K.), and AI147042 (S.-M.K) partially supported this study. The following reagents were obtained from BEI Resources, NIAID, NIH: mouse adapted A/Fort Monmouth/1/1947 H1N1 (NR-28618), reassortant A/Nanchang/933/1995 H3N2 with A/PR8 backbone (NR-3692), A/Hong Kong/1/1968 H3N2 (NR-28634), and from IRR (International Reagent Resource): A/Hong Kong/1073/99 H9N2 influenza virus (FR-732).
© 2022, The Author(s).
All Science Journal Classification (ASJC) codes
- Infectious Diseases
- Pharmacology (medical)