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T Cell Chemo-Vaccination Effects after Repeated Mucosal SHIV Exposures and Oral Pre-Exposure Prophylaxis (Chemo-Vaccination by SHIV Exposure during PrEP)

Pre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study... Full description

Journal Title: PLoS ONE 2011, Vol.6(4), p.e19295
Main Author: Kersh, Ellen N
Other Authors: Adams, Debra R , Youngpairoj, Ae S , Luo, Wei , Zheng, Qi , Cong, Mian-er , Aung, Wutyi , Mitchell, James , Otten, Ron , Hendry, R. Michael , Heneine, Walid , McNicholl, Janet , Garcia-Lerma, J. Gerardo
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0019295
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recordid: plos10.1371/journal.pone.0019295
title: T Cell Chemo-Vaccination Effects after Repeated Mucosal SHIV Exposures and Oral Pre-Exposure Prophylaxis (Chemo-Vaccination by SHIV Exposure during PrEP)
format: Article
creator:
  • Kersh, Ellen N
  • Adams, Debra R
  • Youngpairoj, Ae S
  • Luo, Wei
  • Zheng, Qi
  • Cong, Mian-er
  • Aung, Wutyi
  • Mitchell, James
  • Otten, Ron
  • Hendry, R. Michael
  • Heneine, Walid
  • McNicholl, Janet
  • Garcia-Lerma, J. Gerardo
subjects:
  • Research Article
  • Biology
  • Medicine
  • Virology
  • Infectious Diseases
  • Public Health And Epidemiology
  • Microbiology
ispartof: PLoS ONE, 2011, Vol.6(4), p.e19295
description: Pre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIV SF162P3 rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4 + and CD8 + T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/10 6 PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0019295
fulltext: fulltext
issn:
  • 1932-6203
  • 19326203
url: Link


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titleT Cell Chemo-Vaccination Effects after Repeated Mucosal SHIV Exposures and Oral Pre-Exposure Prophylaxis (Chemo-Vaccination by SHIV Exposure during PrEP)
creatorKersh, Ellen N ; Adams, Debra R ; Youngpairoj, Ae S ; Luo, Wei ; Zheng, Qi ; Cong, Mian-er ; Aung, Wutyi ; Mitchell, James ; Otten, Ron ; Hendry, R. Michael ; Heneine, Walid ; McNicholl, Janet ; Garcia-Lerma, J. Gerardo
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identifierE-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0019295
subjectResearch Article ; Biology ; Medicine ; Virology ; Infectious Diseases ; Public Health And Epidemiology ; Microbiology
descriptionPre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIV SF162P3 rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4 + and CD8 + T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/10 6 PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy.
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titleT Cell Chemo-Vaccination Effects after Repeated Mucosal SHIV Exposures and Oral Pre-Exposure Prophylaxis (Chemo-Vaccination by SHIV Exposure during PrEP)
descriptionPre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIV SF162P3 rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4 + and CD8 + T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/10 6 PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy.
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abstractPre-exposure prophylaxis (PrEP) with anti-viral drugs is currently in clinical trials for the prevention of HIV infection. Induction of adaptive immune responses to virus exposures during anti-viral drug administration, i.e., a “chemo-vaccination” effect, could contribute to PrEP efficacy. To study possible chemo-vaccination, we monitored humoral and cellular immune responses in nine rhesus macaques undergoing up to 14 weekly, low-dose SHIV SF162P3 rectal exposures. Six macaques concurrently received PrEP with intermittent, oral Truvada; three were no-PrEP controls. PrEP protected 4 macaques from infection. Two of the four showed evidence of chemo-vaccination, because they developed anti-SHIV CD4 + and CD8 + T cells; SHIV-specific antibodies were not detected. Control macaques showed no anti-SHIV immune responses before infection. Chemo-vaccination-induced T cell responses were robust (up to 3,940 SFU/10 6 PBMCs), predominantly central memory cells, short-lived (≤22 weeks), and appeared intermittently and with changing specificities. The two chemo-vaccinated macaques were virus-challenged again after 28 weeks of rest, after T cell responses had waned. One macaque was not protected from infection. The other macaque concurrently received additional PrEP. It remained uninfected and T cell responses were boosted during the additional virus exposures. In summary, we document and characterize PrEP-induced T cell chemo-vaccination. Although not protective after subsiding in one macaque, chemo-vaccination-induced T cells warrant more comprehensive analysis during peak responses for their ability to prevent or to control infections after additional exposures. Our findings highlight the importance of monitoring these responses in clinical PrEP trials and suggest that a combination of vaccines and PrEP potentially might enhance efficacy.
copSan Francisco, USA
pubPublic Library of Science
doi10.1371/journal.pone.0019295
oafree_for_read
date2011-04-26