HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice

 

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dc.contributor.author Jongwe, Tsungai Ivai en_ZA
dc.contributor.author Chapman, Ros en_ZA
dc.contributor.author Douglass, Nicola en_ZA
dc.contributor.author Chetty, Shivan en_ZA
dc.contributor.author Chege, Gerald en_ZA
dc.contributor.author Williamson, Anna-Lise en_ZA
dc.date.accessioned 2016-10-31T07:38:06Z
dc.date.available 2016-10-31T07:38:06Z
dc.date.issued 2016 en_ZA
dc.identifier.citation Jongwe, T. I., Chapman, R., Douglass, N., Chetty, S., Chege, G., & Williamson, A. L. (2016). HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice. PloS one, 11(7), e0159141. doi:10.1371/journal.pone.0159141 en_ZA
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0159141 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/22357
dc.description.abstract Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG Δ panCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (Gag M ) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-Gag M vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-Gag M and boosting with MVA-Gag M elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-Gag M only and MVA-Gag M only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4 + and CD8 + T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (10 4 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C). en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other HIV-1 en_ZA
dc.subject.other Vaccines en_ZA
dc.subject.other T cells en_ZA
dc.subject.other Vaccination and immunization en_ZA
dc.subject.other Cytotoxic T cells en_ZA
dc.subject.other Enzyme-linked immunoassays en_ZA
dc.subject.other Polymerase chain reaction en_ZA
dc.subject.other Immune response en_ZA
dc.title HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2016 Jongwe et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Jongwe, T. I., Chapman, R., Douglass, N., Chetty, S., Chege, G., & Williamson, A. (2016). HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice. <i>PLoS One</i>, http://hdl.handle.net/11427/22357 en_ZA
dc.identifier.chicagocitation Jongwe, Tsungai Ivai, Ros Chapman, Nicola Douglass, Shivan Chetty, Gerald Chege, and Anna-Lise Williamson "HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/22357 en_ZA
dc.identifier.vancouvercitation Jongwe TI, Chapman R, Douglass N, Chetty S, Chege G, Williamson A. HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice. PLoS One. 2016; http://hdl.handle.net/11427/22357. en_ZA
dc.identifier.ris TY - Journal Article AU - Jongwe, Tsungai Ivai AU - Chapman, Ros AU - Douglass, Nicola AU - Chetty, Shivan AU - Chege, Gerald AU - Williamson, Anna-Lise AB - Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG Δ panCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (Gag M ) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-Gag M vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-Gag M and boosting with MVA-Gag M elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-Gag M only and MVA-Gag M only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4 + and CD8 + T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (10 4 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C). DA - 2016 DB - OpenUCT DO - 10.1371/journal.pone.0159141 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice TI - HIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in mice UR - http://hdl.handle.net/11427/22357 ER - en_ZA


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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.