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.authorJongwe, Tsungai Ivaien_ZA
dc.contributor.authorChapman, Rosen_ZA
dc.contributor.authorDouglass, Nicolaen_ZA
dc.contributor.authorChetty, Shivanen_ZA
dc.contributor.authorChege, Geralden_ZA
dc.contributor.authorWilliamson, Anna-Liseen_ZA
dc.date.accessioned2016-10-31T07:38:06Z
dc.date.available2016-10-31T07:38:06Z
dc.date.issued2016en_ZA
dc.description.abstractOver 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.identifier.apacitationJongwe, 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/11427/22357en_ZA
dc.identifier.chicagocitationJongwe, 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/11427/22357en_ZA
dc.identifier.citationJongwe, 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.0159141en_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
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0159141en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22357
dc.identifier.vancouvercitationJongwe 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.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis 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.holder© 2016 Jongwe et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherVaccination and immunizationen_ZA
dc.subject.otherCytotoxic T cellsen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherPolymerase chain reactionen_ZA
dc.subject.otherImmune responseen_ZA
dc.titleHIV-1 subtype C mosaic Gag expressed by BCG and MVA elicits persistent effector t cell responses in a prime-boost regimen in miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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