Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center
Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost comb...
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Nature Portfolio
2021
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oai:doaj.org-article:63b38173c836479fba679161167f04132021-12-02T13:23:50ZRecombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center10.1038/s41541-020-00277-12059-0105https://doaj.org/article/63b38173c836479fba679161167f04132021-01-01T00:00:00Zhttps://doi.org/10.1038/s41541-020-00277-1https://doaj.org/toc/2059-0105Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors—plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086 C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNAhi) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOShiCD150lo) Tfh-cell subset.Leila EslamizarConstantinos PetrovasDavid J. LeggatKathryn FurrMichelle L. LiftonGail LevineSteven MaChristopher Fletez-BrantWesley HoylandMadhu PrabhakaranSandeep NarpalaKristin BoswellTakuya YamamotoHua-Xin LiaoDavid PickupElizabeth RamsburgLaura SutherlandAdrian McDermottMario RoedererDavid MontefioriRichard A. KoupBarton F. HaynesNorman L. LetvinSampa SantraNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021) |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Leila Eslamizar Constantinos Petrovas David J. Leggat Kathryn Furr Michelle L. Lifton Gail Levine Steven Ma Christopher Fletez-Brant Wesley Hoyland Madhu Prabhakaran Sandeep Narpala Kristin Boswell Takuya Yamamoto Hua-Xin Liao David Pickup Elizabeth Ramsburg Laura Sutherland Adrian McDermott Mario Roederer David Montefiori Richard A. Koup Barton F. Haynes Norman L. Letvin Sampa Santra Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| description |
Abstract The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed that a vector-prime protein boost combined vaccine strategy was better than when used alone. Here we have studied three different priming vectors—plasmid DNA, recombinant MVA, and recombinant VSV, all encoding clade C transmitted/founder Env 1086 C gp140, for priming three groups of six non-human primates each, followed by a protein boost with adjuvanted 1086 C gp120 protein. Our data showed that MVA-priming favors the development of higher antibody binding titers and neutralizing activity compared with other vectors. Analyses of the draining lymph nodes revealed that MVA-prime induced increased germinal center reactivity characterized by higher frequencies of germinal center (PNAhi) B cells, higher frequencies of antigen-specific B-cell responses as well as an increased frequency of the highly differentiated (ICOShiCD150lo) Tfh-cell subset. |
| format |
article |
| author |
Leila Eslamizar Constantinos Petrovas David J. Leggat Kathryn Furr Michelle L. Lifton Gail Levine Steven Ma Christopher Fletez-Brant Wesley Hoyland Madhu Prabhakaran Sandeep Narpala Kristin Boswell Takuya Yamamoto Hua-Xin Liao David Pickup Elizabeth Ramsburg Laura Sutherland Adrian McDermott Mario Roederer David Montefiori Richard A. Koup Barton F. Haynes Norman L. Letvin Sampa Santra |
| author_facet |
Leila Eslamizar Constantinos Petrovas David J. Leggat Kathryn Furr Michelle L. Lifton Gail Levine Steven Ma Christopher Fletez-Brant Wesley Hoyland Madhu Prabhakaran Sandeep Narpala Kristin Boswell Takuya Yamamoto Hua-Xin Liao David Pickup Elizabeth Ramsburg Laura Sutherland Adrian McDermott Mario Roederer David Montefiori Richard A. Koup Barton F. Haynes Norman L. Letvin Sampa Santra |
| author_sort |
Leila Eslamizar |
| title |
Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| title_short |
Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| title_full |
Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| title_fullStr |
Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| title_full_unstemmed |
Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center |
| title_sort |
recombinant mva-prime elicits neutralizing antibody responses by inducing antigen-specific b cells in the germinal center |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/63b38173c836479fba679161167f0413 |
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