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A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.
PLoS One. 2017; 12(8):e0181738.Plos

Abstract

The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses.

Authors+Show Affiliations

Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America. Department of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.Wisconsin National Primate Research Center, Madison, Wisconsin, United States of America.Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.Department of Pathobiological Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America. Wisconsin National Primate Research Center, Madison, Wisconsin, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28771513

Citation

Florek, Nicholas W., et al. "A Modified Vaccinia Ankara Vaccine Vector Expressing a Mosaic H5 Hemagglutinin Reduces Viral Shedding in Rhesus Macaques." PloS One, vol. 12, no. 8, 2017, pp. e0181738.
Florek NW, Kamlangdee A, Mutschler JP, et al. A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques. PLoS One. 2017;12(8):e0181738.
Florek, N. W., Kamlangdee, A., Mutschler, J. P., Kingstad-Bakke, B., Schultz-Darken, N., Broman, K. W., Osorio, J. E., & Friedrich, T. C. (2017). A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques. PloS One, 12(8), e0181738. https://doi.org/10.1371/journal.pone.0181738
Florek NW, et al. A Modified Vaccinia Ankara Vaccine Vector Expressing a Mosaic H5 Hemagglutinin Reduces Viral Shedding in Rhesus Macaques. PLoS One. 2017;12(8):e0181738. PubMed PMID: 28771513.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques. AU - Florek,Nicholas W, AU - Kamlangdee,Attapon, AU - Mutschler,James P, AU - Kingstad-Bakke,Brock, AU - Schultz-Darken,Nancy, AU - Broman,Karl W, AU - Osorio,Jorge E, AU - Friedrich,Thomas C, Y1 - 2017/08/03/ PY - 2017/01/17/received PY - 2017/07/06/accepted PY - 2017/8/4/entrez PY - 2017/8/5/pubmed PY - 2017/8/29/medline SP - e0181738 EP - e0181738 JF - PloS one JO - PLoS One VL - 12 IS - 8 N2 - The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes. Modified vaccinia Ankara (MVA) expressing this H5 mosaic (MVA-H5M) protected mice against multiple homosubtypic H5N1 strains and a heterosubtypic H1N1 virus. To assess its potential as a human vaccine we evaluated the ability of MVA-H5M to provide heterosubtypic immunity to influenza viruses in a non-human primate model. Rhesus macaques received an initial dose of either MVA-H5M or plasmid DNA encoding H5M, followed by a boost of MVA-H5M, and then were challenged, together with naïve controls, with the heterosubtypic virus A/California/04/2009 (H1N1pdm). Macaques receiving either vaccine regimen cleared H1N1pdm challenge faster than naïve controls. Vaccination with H5M elicited antibodies that bound H1N1pdm HA, but did not neutralize the H1N1pdm challenge virus. Plasma from vaccinated macaques activated NK cells in the presence of H1N1pdm HA, suggesting that vaccination elicited cross-reactive antibodies capable of mediating antibody-dependent cell-mediated cytotoxicity (ADCC). Although HA-specific T cell responses to the MVA-H5M vaccine were weak, responses after challenge were stronger in vaccinated macaques than in control animals. Together these data suggest that mosaic HA antigens may provide a means for inducing broadly cross-reactive immunity to influenza viruses. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/28771513/A_modified_vaccinia_Ankara_vaccine_vector_expressing_a_mosaic_H5_hemagglutinin_reduces_viral_shedding_in_rhesus_macaques_ L2 - https://dx.plos.org/10.1371/journal.pone.0181738 DB - PRIME DP - Unbound Medicine ER -