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Influenza Chimeric Protein (3M2e-3HA2-NP) Adjuvanted with PGA/Alum Confers Cross-Protection against Heterologous Influenza A Viruses

Journal of Microbiology and Biotechnology 2021년 31권 2호 p.304 ~ 316
곽채원, Nguyen Quyen Thi, 김재무, 김태환, 부하령,
소속 상세정보
곽채원 ( Kwak Chae-Won ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center
 ( Nguyen Quyen Thi ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center
김재무 ( Kim Jae-Moo ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center
김태환 ( Kim Tae-Hwan ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center
부하령 ( Poo Ha-Ryoung ) - Korea Research Institute of Bioscience and Biotechnology Infectious Disease Research Center

Abstract


Vaccination is the most effective way to prevent influenza virus infections. However, conventional vaccines based on hemagglutinin (HA) have to be annually updated because the HA of influenza viruses constantly mutates. In this study, we produced a 3M2e?3HA2?NP chimeric protein as a vaccine antigen candidate using an Escherichia coli expression system. The vaccination of chimeric protein (15 μg) conferred complete protection against A/Puerto Rico/8/1934 (H1N1; PR8) in mice. It strongly induced influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity. To spare the dose and enhance the cross-reactivity of the chimeric, we used a complex of poly-γ-glutamic acid and alum (PGA/alum) as an adjuvant. PGA/alum-adjuvanted, low-dose chimeric protein (1 or 5 μg) exhibited higher cross-protective effects against influenza A viruses (PR8, CA04, and H3N2) compared with those of chimeric alone or alum-adjuvanted proteins in vaccinated mice. Moreover, the depletion of CD4+ T, CD8+ T, and NK cells reduced the survival rate and efficacy of the PGA/alum-adjuvanted chimeric protein. Collectively, the vaccination of PGA/alum-adjuvanted chimeric protein induced strong protection efficacy against homologous and heterologous influenza viruses in mice, which suggests that it may be a promising universal influenza vaccine candidate.

키워드

Influenza virus; universal vaccine; adjuvant; cross-reactivity

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