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Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus.
Antiviral Res. 2015 Oct; 122:82-90.AR

Abstract

Current influenza vaccines are less efficacious against antigenically different influenza A viruses. This study presents an approach to overcome strain-specific protection, using a strategy of co-immunization with seasonal H3N2 split vaccine and yeast-expressed soluble proteins of a tandem repeat containing heterologous influenza M2 ectodomains (M2e5x). Co-immunization with both vaccines in mice was superior to either vaccine alone in inducing cross protection against heterologous H3N2 virus by raising M2e-specific humoral and cellular immune responses toward a T-helper type 1 profile inducing IgG2a isotype antibodies as well as interferon-γ-producing cells in systemic and mucosal sites. In addition, co-immunization sera were found to confer cross-protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. A mechanistic study provides evidence that activation of dendritic cells by co-stimulation with M2e5x and split vaccine was associated with the proliferation of CD4(+) T cells. Our results suggest that a strategy of co-immunization with seasonal split and M2e5x protein vaccines could be a promising approach for overcoming the limitation of strain-specific protection by current influenza vaccination.

Authors+Show Affiliations

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Animal and Plant Quarantine Agency, 175 Anyangro, Anyang, Gyeonggi-do 430-757, Republic of Korea.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, Republic of Korea.BEAMS Biotechnology Co. Ltd., Seongnam, Gyeonggi-do, Republic of Korea.Mogam Biotechnology Research Institute, Yongin, Gyeonggi-do, Republic of Korea.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. Electronic address: skang24@gsu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26248203

Citation

Lee, Yu-Na, et al. "Co-immunization With Tandem Repeat Heterologous M2 Extracellular Proteins Overcomes Strain-specific Protection of Split Vaccine Against Influenza a Virus." Antiviral Research, vol. 122, 2015, pp. 82-90.
Lee YN, Kim MC, Lee YT, et al. Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus. Antiviral Res. 2015;122:82-90.
Lee, Y. N., Kim, M. C., Lee, Y. T., Kim, Y. J., Lee, J., Kim, C., Ha, S. H., & Kang, S. M. (2015). Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus. Antiviral Research, 122, 82-90. https://doi.org/10.1016/j.antiviral.2015.08.001
Lee YN, et al. Co-immunization With Tandem Repeat Heterologous M2 Extracellular Proteins Overcomes Strain-specific Protection of Split Vaccine Against Influenza a Virus. Antiviral Res. 2015;122:82-90. PubMed PMID: 26248203.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Co-immunization with tandem repeat heterologous M2 extracellular proteins overcomes strain-specific protection of split vaccine against influenza A virus. AU - Lee,Yu-Na, AU - Kim,Min-Chul, AU - Lee,Young-Tae, AU - Kim,Yu-Jin, AU - Lee,Jongsang, AU - Kim,Cheol, AU - Ha,Suk-Hoon, AU - Kang,Sang-Moo, Y1 - 2015/08/04/ PY - 2015/02/03/received PY - 2015/07/29/revised PY - 2015/08/03/accepted PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2016/6/23/medline KW - AS04 KW - Influenza virus KW - M2e5x KW - Protein KW - Split vaccine SP - 82 EP - 90 JF - Antiviral research JO - Antiviral Res VL - 122 N2 - Current influenza vaccines are less efficacious against antigenically different influenza A viruses. This study presents an approach to overcome strain-specific protection, using a strategy of co-immunization with seasonal H3N2 split vaccine and yeast-expressed soluble proteins of a tandem repeat containing heterologous influenza M2 ectodomains (M2e5x). Co-immunization with both vaccines in mice was superior to either vaccine alone in inducing cross protection against heterologous H3N2 virus by raising M2e-specific humoral and cellular immune responses toward a T-helper type 1 profile inducing IgG2a isotype antibodies as well as interferon-γ-producing cells in systemic and mucosal sites. In addition, co-immunization sera were found to confer cross-protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. A mechanistic study provides evidence that activation of dendritic cells by co-stimulation with M2e5x and split vaccine was associated with the proliferation of CD4(+) T cells. Our results suggest that a strategy of co-immunization with seasonal split and M2e5x protein vaccines could be a promising approach for overcoming the limitation of strain-specific protection by current influenza vaccination. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/26248203/Co_immunization_with_tandem_repeat_heterologous_M2_extracellular_proteins_overcomes_strain_specific_protection_of_split_vaccine_against_influenza_A_virus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(15)00174-6 DB - PRIME DP - Unbound Medicine ER -