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Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs
A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strat...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674457/ https://www.ncbi.nlm.nih.gov/pubmed/33298954 http://dx.doi.org/10.1038/s41541-020-00252-w |
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author | Blasi, Maria Negri, Donatella Saunders, Kevin O. Baker, Erich J. Stadtler, Hannah LaBranche, Celia Mildenberg, Benjamin Morton, Georgeanna Ciarla, Andrew Shen, Xiaoying Wang, Yunfei Rountree, Wes Balakumaran, Bala Santra, Sampa Haynes, Barton F. Moody, Anthony M. Cara, Andrea Klotman, Mary E. |
author_facet | Blasi, Maria Negri, Donatella Saunders, Kevin O. Baker, Erich J. Stadtler, Hannah LaBranche, Celia Mildenberg, Benjamin Morton, Georgeanna Ciarla, Andrew Shen, Xiaoying Wang, Yunfei Rountree, Wes Balakumaran, Bala Santra, Sampa Haynes, Barton F. Moody, Anthony M. Cara, Andrea Klotman, Mary E. |
author_sort | Blasi, Maria |
collection | PubMed |
description | A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms. |
format | Online Article Text |
id | pubmed-7674457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-76744572020-11-20 Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs Blasi, Maria Negri, Donatella Saunders, Kevin O. Baker, Erich J. Stadtler, Hannah LaBranche, Celia Mildenberg, Benjamin Morton, Georgeanna Ciarla, Andrew Shen, Xiaoying Wang, Yunfei Rountree, Wes Balakumaran, Bala Santra, Sampa Haynes, Barton F. Moody, Anthony M. Cara, Andrea Klotman, Mary E. NPJ Vaccines Article A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/− protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms. Nature Publishing Group UK 2020-11-18 /pmc/articles/PMC7674457/ /pubmed/33298954 http://dx.doi.org/10.1038/s41541-020-00252-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Blasi, Maria Negri, Donatella Saunders, Kevin O. Baker, Erich J. Stadtler, Hannah LaBranche, Celia Mildenberg, Benjamin Morton, Georgeanna Ciarla, Andrew Shen, Xiaoying Wang, Yunfei Rountree, Wes Balakumaran, Bala Santra, Sampa Haynes, Barton F. Moody, Anthony M. Cara, Andrea Klotman, Mary E. Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title | Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title_full | Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title_fullStr | Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title_full_unstemmed | Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title_short | Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs |
title_sort | immunogenicity, safety, and efficacy of sequential immunizations with an siv-based idlv expressing ch505 envs |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674457/ https://www.ncbi.nlm.nih.gov/pubmed/33298954 http://dx.doi.org/10.1038/s41541-020-00252-w |
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