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Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates

The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectore...

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Autores principales: Xiao, Peng, Dienger-Stambaugh, Krista, Chen, Xuemin, Wei, Huiling, Phan, Shannon, Beavis, Ashley C., Singh, Karnail, Adhikary, Nihar R. Deb, Tiwari, Pooja, Villinger, Francois, He, Biao, Spearman, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946978/
https://www.ncbi.nlm.nih.gov/pubmed/33717130
http://dx.doi.org/10.3389/fimmu.2021.623996
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author Xiao, Peng
Dienger-Stambaugh, Krista
Chen, Xuemin
Wei, Huiling
Phan, Shannon
Beavis, Ashley C.
Singh, Karnail
Adhikary, Nihar R. Deb
Tiwari, Pooja
Villinger, Francois
He, Biao
Spearman, Paul
author_facet Xiao, Peng
Dienger-Stambaugh, Krista
Chen, Xuemin
Wei, Huiling
Phan, Shannon
Beavis, Ashley C.
Singh, Karnail
Adhikary, Nihar R. Deb
Tiwari, Pooja
Villinger, Francois
He, Biao
Spearman, Paul
author_sort Xiao, Peng
collection PubMed
description The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectored vaccines have shown protection against influenza, RSV, and other human pathogens. Here, we generated PIV5 vaccines expressing HIV envelope (Env) and SIV Gag and administered them intranasally to macaques, followed by boosting with virus-like particles (VLPs) containing trimeric HIV Env. Moreover, we compared the immune responses generated by PIV5-SHIV prime/VLPs boost regimen in naïve vs a control group in which pre-existing immunity to the PIV5 vector was established. We demonstrate for the first time that intranasal administration of PIV5-based HIV vaccines is safe, well-tolerated and immunogenic, and that boosting with adjuvanted trimeric Env VLPs enhances humoral and cellular immune responses. The PIV5 prime/VLPs boost regimen induced robust and durable systemic and mucosal Env-specific antibody titers with functional activities including ADCC and neutralization. This regimen also induced highly polyfunctional antigen-specific T cell responses. Importantly, we show that diminished responses due to PIV5 pre-existing immunity can be overcome in part with VLP protein boosts. Overall, these results establish that PIV5-based HIV vaccine candidates are promising and warrant further investigation including moving on to primate challenge studies.
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spelling pubmed-79469782021-03-12 Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates Xiao, Peng Dienger-Stambaugh, Krista Chen, Xuemin Wei, Huiling Phan, Shannon Beavis, Ashley C. Singh, Karnail Adhikary, Nihar R. Deb Tiwari, Pooja Villinger, Francois He, Biao Spearman, Paul Front Immunol Immunology The search for a preventive vaccine against HIV infection remains an ongoing challenge, indicating the need for novel approaches. Parainfluenza virus 5 (PIV5) is a paramyxovirus replicating in the upper airways that is not associated with any animal or human pathology. In animal models, PIV5-vectored vaccines have shown protection against influenza, RSV, and other human pathogens. Here, we generated PIV5 vaccines expressing HIV envelope (Env) and SIV Gag and administered them intranasally to macaques, followed by boosting with virus-like particles (VLPs) containing trimeric HIV Env. Moreover, we compared the immune responses generated by PIV5-SHIV prime/VLPs boost regimen in naïve vs a control group in which pre-existing immunity to the PIV5 vector was established. We demonstrate for the first time that intranasal administration of PIV5-based HIV vaccines is safe, well-tolerated and immunogenic, and that boosting with adjuvanted trimeric Env VLPs enhances humoral and cellular immune responses. The PIV5 prime/VLPs boost regimen induced robust and durable systemic and mucosal Env-specific antibody titers with functional activities including ADCC and neutralization. This regimen also induced highly polyfunctional antigen-specific T cell responses. Importantly, we show that diminished responses due to PIV5 pre-existing immunity can be overcome in part with VLP protein boosts. Overall, these results establish that PIV5-based HIV vaccine candidates are promising and warrant further investigation including moving on to primate challenge studies. Frontiers Media S.A. 2021-02-25 /pmc/articles/PMC7946978/ /pubmed/33717130 http://dx.doi.org/10.3389/fimmu.2021.623996 Text en Copyright © 2021 Xiao, Dienger-Stambaugh, Chen, Wei, Phan, Beavis, Singh, Adhikary, Tiwari, Villinger, He and Spearman http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Xiao, Peng
Dienger-Stambaugh, Krista
Chen, Xuemin
Wei, Huiling
Phan, Shannon
Beavis, Ashley C.
Singh, Karnail
Adhikary, Nihar R. Deb
Tiwari, Pooja
Villinger, Francois
He, Biao
Spearman, Paul
Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title_full Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title_fullStr Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title_full_unstemmed Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title_short Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates
title_sort parainfluenza virus 5 priming followed by siv/hiv virus-like-particle boosting induces potent and durable immune responses in nonhuman primates
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946978/
https://www.ncbi.nlm.nih.gov/pubmed/33717130
http://dx.doi.org/10.3389/fimmu.2021.623996
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