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A 30-year journey of trial and error towards a tolerogenic AIDS vaccine

Since 1985, we have tested several immunological approaches to suppressing HIV replication in HIV-infected patients and to prevent HIV acquisition in uninfected people. Here, after briefly reviewing our studies on immunosuppressive treatments and therapeutic dendritic cell-based therapies, we examin...

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Autores principales: Andrieu, Jean-Marie, Lu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096718/
https://www.ncbi.nlm.nih.gov/pubmed/30043201
http://dx.doi.org/10.1007/s00705-018-3936-1
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author Andrieu, Jean-Marie
Lu, Wei
author_facet Andrieu, Jean-Marie
Lu, Wei
author_sort Andrieu, Jean-Marie
collection PubMed
description Since 1985, we have tested several immunological approaches to suppressing HIV replication in HIV-infected patients and to prevent HIV acquisition in uninfected people. Here, after briefly reviewing our studies on immunosuppressive treatments and therapeutic dendritic cell-based therapies, we examine in more detail our work on the tolerogenic vaccines we developed against AIDS in Chinese macaques. The vaccine consisted of inactivated SIVmac239 particles adjuvanted with the Bacillus of Calmette and Guerin (BCG), Lactobacillus plantarum (LP), or Lactobacillus rhamnosus (LR). Without adjuvant, the vaccine administered by the intragastric route induced the usual simian immunodeficiency virus (SIV)-specific humoral immune responses but no post-challenge protection. In contrast, out of 24 macaques that were immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to 5 years, while all control macaques were infected. On the other hand, all macaques of Indian origin that were immunized with the same adjuvanted vaccine were not protected. We then discovered that vaccinated Chinese macaques developed a previously unrecognized class of non-cytolytic MHC-Ib/E-restricted CD8(+) T cells (or CD8(+) T-Regs) that suppressed the activation of SIV RNA-infected CD4(+) T cells and thereby inhibited the (activation-dependent) reverse transcription of the virus and prevented the establishment of SIV infection. Finally, we found a similar population of HLA-E-restricted CD8(+) T-Regs in human elite controllers (a small group of HIV-infected patients whose viral replication is naturally inhibited). Ex vivo, their CD8(+) T-Regs suppressed viral replication in the same manner as those of vaccinated Chinese macaques. It is noteworthy that all of these elite controllers had a homo- or heterozygous HLA-Bw4-80I genotype. Taking into account the longevity and the high percentage of vaccine-protected Chinese macaques together with the concomitant identification of a robust ex vivo correlate of protection and the discovery of similar CD8(+) T-Regs in human elite controllers, preventive and therapeutic HIV vaccines should be envisaged in humans.
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spelling pubmed-60967182018-08-24 A 30-year journey of trial and error towards a tolerogenic AIDS vaccine Andrieu, Jean-Marie Lu, Wei Arch Virol In honor of Marc van Regenmortel Since 1985, we have tested several immunological approaches to suppressing HIV replication in HIV-infected patients and to prevent HIV acquisition in uninfected people. Here, after briefly reviewing our studies on immunosuppressive treatments and therapeutic dendritic cell-based therapies, we examine in more detail our work on the tolerogenic vaccines we developed against AIDS in Chinese macaques. The vaccine consisted of inactivated SIVmac239 particles adjuvanted with the Bacillus of Calmette and Guerin (BCG), Lactobacillus plantarum (LP), or Lactobacillus rhamnosus (LR). Without adjuvant, the vaccine administered by the intragastric route induced the usual simian immunodeficiency virus (SIV)-specific humoral immune responses but no post-challenge protection. In contrast, out of 24 macaques that were immunized with the adjuvanted vaccine and challenged intrarectally with SIVmac239 or SIVB670, 23 were sterilely protected for up to 5 years, while all control macaques were infected. On the other hand, all macaques of Indian origin that were immunized with the same adjuvanted vaccine were not protected. We then discovered that vaccinated Chinese macaques developed a previously unrecognized class of non-cytolytic MHC-Ib/E-restricted CD8(+) T cells (or CD8(+) T-Regs) that suppressed the activation of SIV RNA-infected CD4(+) T cells and thereby inhibited the (activation-dependent) reverse transcription of the virus and prevented the establishment of SIV infection. Finally, we found a similar population of HLA-E-restricted CD8(+) T-Regs in human elite controllers (a small group of HIV-infected patients whose viral replication is naturally inhibited). Ex vivo, their CD8(+) T-Regs suppressed viral replication in the same manner as those of vaccinated Chinese macaques. It is noteworthy that all of these elite controllers had a homo- or heterozygous HLA-Bw4-80I genotype. Taking into account the longevity and the high percentage of vaccine-protected Chinese macaques together with the concomitant identification of a robust ex vivo correlate of protection and the discovery of similar CD8(+) T-Regs in human elite controllers, preventive and therapeutic HIV vaccines should be envisaged in humans. Springer Vienna 2018-07-24 2018 /pmc/articles/PMC6096718/ /pubmed/30043201 http://dx.doi.org/10.1007/s00705-018-3936-1 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle In honor of Marc van Regenmortel
Andrieu, Jean-Marie
Lu, Wei
A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title_full A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title_fullStr A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title_full_unstemmed A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title_short A 30-year journey of trial and error towards a tolerogenic AIDS vaccine
title_sort 30-year journey of trial and error towards a tolerogenic aids vaccine
topic In honor of Marc van Regenmortel
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096718/
https://www.ncbi.nlm.nih.gov/pubmed/30043201
http://dx.doi.org/10.1007/s00705-018-3936-1
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