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Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques

HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination i...

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Autores principales: Pahar, Bapi, Gray, Wayne, Fahlberg, Marissa, Grasperge, Brooke, Hunter, Meredith, Das, Arpita, Mabee, Christopher, Aye, Pyone Pyone, Schiro, Faith, Hensley, Krystle, Ratnayake, Aneeka, Goff, Kelly, LaBranche, Celia, Shen, Xiaoying, Tomaras, Georgia D., DeMarco, C. Todd, Montefiori, David, Kissinger, Patricia, Marx, Preston A., Traina-Dorge, Vicki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853323/
https://www.ncbi.nlm.nih.gov/pubmed/36560823
http://dx.doi.org/10.3390/v14122819
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author Pahar, Bapi
Gray, Wayne
Fahlberg, Marissa
Grasperge, Brooke
Hunter, Meredith
Das, Arpita
Mabee, Christopher
Aye, Pyone Pyone
Schiro, Faith
Hensley, Krystle
Ratnayake, Aneeka
Goff, Kelly
LaBranche, Celia
Shen, Xiaoying
Tomaras, Georgia D.
DeMarco, C. Todd
Montefiori, David
Kissinger, Patricia
Marx, Preston A.
Traina-Dorge, Vicki
author_facet Pahar, Bapi
Gray, Wayne
Fahlberg, Marissa
Grasperge, Brooke
Hunter, Meredith
Das, Arpita
Mabee, Christopher
Aye, Pyone Pyone
Schiro, Faith
Hensley, Krystle
Ratnayake, Aneeka
Goff, Kelly
LaBranche, Celia
Shen, Xiaoying
Tomaras, Georgia D.
DeMarco, C. Todd
Montefiori, David
Kissinger, Patricia
Marx, Preston A.
Traina-Dorge, Vicki
author_sort Pahar, Bapi
collection PubMed
description HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination induced anti-SIV IgG responses and neutralizing antibodies were found in all vaccinated RMs. Three of the eight vaccinated RM remained uninfected (vaccinated and protected, VP) after 13 repeated challenges with the pathogenic SIVmac251-CX-1. The remaining five vaccinated and infected (VI) macaques had significantly reduced plasma viral loads compared with the infected controls (IC). A significant increase in systemic central memory CD4+ T cells and mucosal CD8+ effector memory T-cell responses was detected in vaccinated RMs compared to controls. Variability in lymph node SIV-Gag and Env specific CD4+ and CD8+ T cell cytokine responses were detected in the VI RMs while all three VP RMs had more durable cytokine responses following vaccination and prior to challenge. VI RMs demonstrated predominately SIV-specific monofunctional cytokine responses while the VP RMs generated polyfunctional cytokine responses. This study demonstrates that varicella virus-vectored SIV vaccination with protein boosts induces a 37.5% efficacy rate against pathogenic SIV challenge by generating mucosal memory, virus specific neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses.
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spelling pubmed-98533232023-01-21 Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques Pahar, Bapi Gray, Wayne Fahlberg, Marissa Grasperge, Brooke Hunter, Meredith Das, Arpita Mabee, Christopher Aye, Pyone Pyone Schiro, Faith Hensley, Krystle Ratnayake, Aneeka Goff, Kelly LaBranche, Celia Shen, Xiaoying Tomaras, Georgia D. DeMarco, C. Todd Montefiori, David Kissinger, Patricia Marx, Preston A. Traina-Dorge, Vicki Viruses Article HIV vaccine mediated efficacy, using an expanded live attenuated recombinant varicella virus-vectored SIV rSVV-SIVgag/env vaccine prime with adjuvanted SIV-Env and SIV-Gag protein boosts, was evaluated in a female rhesus macaques (RM) model against repeated intravaginal SIV challenges. Vaccination induced anti-SIV IgG responses and neutralizing antibodies were found in all vaccinated RMs. Three of the eight vaccinated RM remained uninfected (vaccinated and protected, VP) after 13 repeated challenges with the pathogenic SIVmac251-CX-1. The remaining five vaccinated and infected (VI) macaques had significantly reduced plasma viral loads compared with the infected controls (IC). A significant increase in systemic central memory CD4+ T cells and mucosal CD8+ effector memory T-cell responses was detected in vaccinated RMs compared to controls. Variability in lymph node SIV-Gag and Env specific CD4+ and CD8+ T cell cytokine responses were detected in the VI RMs while all three VP RMs had more durable cytokine responses following vaccination and prior to challenge. VI RMs demonstrated predominately SIV-specific monofunctional cytokine responses while the VP RMs generated polyfunctional cytokine responses. This study demonstrates that varicella virus-vectored SIV vaccination with protein boosts induces a 37.5% efficacy rate against pathogenic SIV challenge by generating mucosal memory, virus specific neutralizing antibodies, binding antibodies, and polyfunctional T-cell responses. MDPI 2022-12-17 /pmc/articles/PMC9853323/ /pubmed/36560823 http://dx.doi.org/10.3390/v14122819 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pahar, Bapi
Gray, Wayne
Fahlberg, Marissa
Grasperge, Brooke
Hunter, Meredith
Das, Arpita
Mabee, Christopher
Aye, Pyone Pyone
Schiro, Faith
Hensley, Krystle
Ratnayake, Aneeka
Goff, Kelly
LaBranche, Celia
Shen, Xiaoying
Tomaras, Georgia D.
DeMarco, C. Todd
Montefiori, David
Kissinger, Patricia
Marx, Preston A.
Traina-Dorge, Vicki
Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title_full Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title_fullStr Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title_full_unstemmed Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title_short Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques
title_sort recombinant simian varicella virus-simian immunodeficiency virus vaccine induces t and b cell functions and provides partial protection against repeated mucosal siv challenges in rhesus macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853323/
https://www.ncbi.nlm.nih.gov/pubmed/36560823
http://dx.doi.org/10.3390/v14122819
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