A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine
Authors
Jeeva Subbiah ; Judy Oh ; Ki-Hye Kim ; Chong-Hyun Shin ; Bo Ryoung Park ; Noopur Bhatnagar ; Baik-Lin Seong ; Bao-Zhong Wang ; Sang-Moo Kang
Citation
NPJ VACCINES, Vol.7(1) : 68, 2022-06
Journal Title
NPJ VACCINES
Issue Date
2022-06
Abstract
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.