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Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate.
Antiviral Res. 2017 Dec; 148:43-52.AR

Abstract

Current influenza vaccines provide hemagglutinin (HA) strain-specific protection. To improve cross protection, we engineered replication-competent influenza A virus to express tandem repeats of heterologous M2 extracellular (M2e) domains in a chimeric HA. M2e epitopes conjugated to HA glycoproteins (M2e4x-HA) were found to be expressed on the surfaces of a replicable influenza virus as examined by electron microscopy. The recombinant influenza virus containing M2e4x-HA was moderately attenuated but superior to the parental virus in inducing M2e specific antibodies without compromising HA immunogenicity. Recombinant influenza virus immune mice showed better cross protection than parental virus immune mice. Immune sera from the mice with inoculation of live recombinant influenza virus expressing M2e4x-HA were effective in conferring protection against H1, H3, and H5 subtype influenza viruses. This study indicates that recombinant influenza virus expressing conserved protective epitopes in an HA chimeric form can provide a new approach for improving the efficacy of influenza vaccines.

Authors+Show Affiliations

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA; Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, Republic of Korea.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA; Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, Republic of Korea.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.Department of Chemical and Materials Engineering, University of Alberta, AB, T6G 2V4, Canada.Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, 39660, 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

Language

eng

PubMed ID

29107058

Citation

Kim, Min-Chul, et al. "Immunogenicity and Efficacy of Replication-competent Recombinant Influenza Virus Carrying Multimeric M2 Extracellular Domains in a Chimeric Hemagglutinin Conjugate." Antiviral Research, vol. 148, 2017, pp. 43-52.
Kim MC, Lee YN, Kim YJ, et al. Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate. Antiviral Res. 2017;148:43-52.
Kim, M. C., Lee, Y. N., Kim, Y. J., Choi, H. J., Kim, K. H., Lee, Y. J., & Kang, S. M. (2017). Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate. Antiviral Research, 148, 43-52. https://doi.org/10.1016/j.antiviral.2017.10.018
Kim MC, et al. Immunogenicity and Efficacy of Replication-competent Recombinant Influenza Virus Carrying Multimeric M2 Extracellular Domains in a Chimeric Hemagglutinin Conjugate. Antiviral Res. 2017;148:43-52. PubMed PMID: 29107058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunogenicity and efficacy of replication-competent recombinant influenza virus carrying multimeric M2 extracellular domains in a chimeric hemagglutinin conjugate. AU - Kim,Min-Chul, AU - Lee,Yu-Na, AU - Kim,Yu-Jin, AU - Choi,Hyo-Jick, AU - Kim,Ki-Hye, AU - Lee,Youn-Jeong, AU - Kang,Sang-Moo, Y1 - 2017/10/26/ PY - 2017/04/20/received PY - 2017/10/17/revised PY - 2017/10/23/accepted PY - 2017/11/7/pubmed PY - 2018/7/12/medline PY - 2017/11/7/entrez KW - Chimeric M2e4x-HA protein KW - Recombinant influenza virus KW - Universal influenza vaccine KW - Viral vector SP - 43 EP - 52 JF - Antiviral research JO - Antiviral Res VL - 148 N2 - Current influenza vaccines provide hemagglutinin (HA) strain-specific protection. To improve cross protection, we engineered replication-competent influenza A virus to express tandem repeats of heterologous M2 extracellular (M2e) domains in a chimeric HA. M2e epitopes conjugated to HA glycoproteins (M2e4x-HA) were found to be expressed on the surfaces of a replicable influenza virus as examined by electron microscopy. The recombinant influenza virus containing M2e4x-HA was moderately attenuated but superior to the parental virus in inducing M2e specific antibodies without compromising HA immunogenicity. Recombinant influenza virus immune mice showed better cross protection than parental virus immune mice. Immune sera from the mice with inoculation of live recombinant influenza virus expressing M2e4x-HA were effective in conferring protection against H1, H3, and H5 subtype influenza viruses. This study indicates that recombinant influenza virus expressing conserved protective epitopes in an HA chimeric form can provide a new approach for improving the efficacy of influenza vaccines. SN - 1872-9096 UR - https://www.unboundmedicine.com/medline/citation/29107058/Immunogenicity_and_efficacy_of_replication_competent_recombinant_influenza_virus_carrying_multimeric_M2_extracellular_domains_in_a_chimeric_hemagglutinin_conjugate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-3542(17)30296-6 DB - PRIME DP - Unbound Medicine ER -