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Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope.
Virology. 2020 11; 550:51-60.V

Abstract

Influenza virus neuraminidase (NA) contains a universally conserved epitope (NAe, NA222-230). However, no studies have reported vaccines targeting this NA conserved epitope and inducing antibodies recognizing NAe. The extracellular domain of M2 (M2e) is considered as an attractive target for a universal influenza vaccine. We generated recombinant influenza H1N1 viruses expressing conserved epitopes in hemagglutinin (HA) molecules: NAe (NAe-HA) or M2e (M2e-HA) within the HA head domain. Inactivated recombinant NAe-HA and M2e-HA viruses were more effective in inducing IgG antibodies specific for an inserted conserved epitope than live recombinant virus. Recombinant inactivated M2e-HA virus vaccination induced cross protection against H3N2 virus with less weight loss compared to NAe-HA and was more effective in inducing humoral and cellular M2e immune responses. This study provides insight into developing recombinant influenza virus vaccines compatible with current platforms to induce antibody responses to conserved poorly immunogenic epitopes.

Authors+Show Affiliations

Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; CARESIDE Co., Ltd., Seongnam, Gyeonggi-do, Republic of Korea.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA. Electronic address: skang24@gsu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

32882637

Citation

Kim, Ki-Hye, et al. "Cross Protection By Inactivated Recombinant Influenza Viruses Containing Chimeric Hemagglutinin Conjugates With a Conserved Neuraminidase or M2 Ectodomain Epitope." Virology, vol. 550, 2020, pp. 51-60.
Kim KH, Jung YJ, Lee Y, et al. Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope. Virology. 2020;550:51-60.
Kim, K. H., Jung, Y. J., Lee, Y., Park, B. R., Oh, J., Lee, Y. N., Kim, M. C., Jeeva, S., & Kang, S. M. (2020). Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope. Virology, 550, 51-60. https://doi.org/10.1016/j.virol.2020.08.003
Kim KH, et al. Cross Protection By Inactivated Recombinant Influenza Viruses Containing Chimeric Hemagglutinin Conjugates With a Conserved Neuraminidase or M2 Ectodomain Epitope. Virology. 2020;550:51-60. PubMed PMID: 32882637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope. AU - Kim,Ki-Hye, AU - Jung,Yu-Jin, AU - Lee,Youri, AU - Park,Bo Ryoung, AU - Oh,Judy, AU - Lee,Yu-Na, AU - Kim,Min-Chul, AU - Jeeva,Subbiah, AU - Kang,Sang-Moo, Y1 - 2020/08/22/ PY - 2020/02/07/received PY - 2020/08/05/revised PY - 2020/08/12/accepted PY - 2021/11/01/pmc-release PY - 2020/9/4/pubmed PY - 2021/2/25/medline PY - 2020/9/4/entrez KW - Cross protection KW - Heterosubtypic immunity KW - M2 extracellular domain epitope KW - Neuraminidase epitope KW - Recombinant chimeric influenza virus SP - 51 EP - 60 JF - Virology JO - Virology VL - 550 N2 - Influenza virus neuraminidase (NA) contains a universally conserved epitope (NAe, NA222-230). However, no studies have reported vaccines targeting this NA conserved epitope and inducing antibodies recognizing NAe. The extracellular domain of M2 (M2e) is considered as an attractive target for a universal influenza vaccine. We generated recombinant influenza H1N1 viruses expressing conserved epitopes in hemagglutinin (HA) molecules: NAe (NAe-HA) or M2e (M2e-HA) within the HA head domain. Inactivated recombinant NAe-HA and M2e-HA viruses were more effective in inducing IgG antibodies specific for an inserted conserved epitope than live recombinant virus. Recombinant inactivated M2e-HA virus vaccination induced cross protection against H3N2 virus with less weight loss compared to NAe-HA and was more effective in inducing humoral and cellular M2e immune responses. This study provides insight into developing recombinant influenza virus vaccines compatible with current platforms to induce antibody responses to conserved poorly immunogenic epitopes. SN - 1096-0341 UR - https://www.unboundmedicine.com/medline/citation/32882637/Cross_protection_by_inactivated_recombinant_influenza_viruses_containing_chimeric_hemagglutinin_conjugates_with_a_conserved_neuraminidase_or_M2_ectodomain_epitope_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(20)30156-2 DB - PRIME DP - Unbound Medicine ER -