Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo

Paul R. Gorry, Dale A. McPhee, Erin Verity, Wayne B. Dyer, Steven L. Wesselingh, Jennifer Learmont, John S. Sullivan, Michael Roche, John J. Zaunders, Dana Gabuzda, Suzanne M. Crowe, John Mills, Sharon R. Lewin, Bruce J. Brew, Anthony L. Cunningham, Melissa J. Churchill

Research output: Contribution to journalReview article

49 Citations (Scopus)

Abstract

In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection.

LanguageEnglish
Article number66
JournalRetrovirology
Volume4
DOIs
Publication statusPublished - 23 Sep 2007

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Gorry, P. R., McPhee, D. A., Verity, E., Dyer, W. B., Wesselingh, S. L., Learmont, J., ... Churchill, M. J. (2007). Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. Retrovirology, 4, [66]. https://doi.org/10.1186/1742-4690-4-66
Gorry, Paul R. ; McPhee, Dale A. ; Verity, Erin ; Dyer, Wayne B. ; Wesselingh, Steven L. ; Learmont, Jennifer ; Sullivan, John S. ; Roche, Michael ; Zaunders, John J. ; Gabuzda, Dana ; Crowe, Suzanne M. ; Mills, John ; Lewin, Sharon R. ; Brew, Bruce J. ; Cunningham, Anthony L. ; Churchill, Melissa J. / Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. In: Retrovirology. 2007 ; Vol. 4.
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abstract = "In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection.",
author = "Gorry, {Paul R.} and McPhee, {Dale A.} and Erin Verity and Dyer, {Wayne B.} and Wesselingh, {Steven L.} and Jennifer Learmont and Sullivan, {John S.} and Michael Roche and Zaunders, {John J.} and Dana Gabuzda and Crowe, {Suzanne M.} and John Mills and Lewin, {Sharon R.} and Brew, {Bruce J.} and Cunningham, {Anthony L.} and Churchill, {Melissa J.}",
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Gorry, PR, McPhee, DA, Verity, E, Dyer, WB, Wesselingh, SL, Learmont, J, Sullivan, JS, Roche, M, Zaunders, JJ, Gabuzda, D, Crowe, SM, Mills, J, Lewin, SR, Brew, BJ, Cunningham, AL & Churchill, MJ 2007, 'Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo', Retrovirology, vol. 4, 66. https://doi.org/10.1186/1742-4690-4-66

Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo. / Gorry, Paul R.; McPhee, Dale A.; Verity, Erin; Dyer, Wayne B.; Wesselingh, Steven L.; Learmont, Jennifer; Sullivan, John S.; Roche, Michael; Zaunders, John J.; Gabuzda, Dana; Crowe, Suzanne M.; Mills, John; Lewin, Sharon R.; Brew, Bruce J.; Cunningham, Anthony L.; Churchill, Melissa J.

In: Retrovirology, Vol. 4, 66, 23.09.2007.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo

AU - Gorry, Paul R.

AU - McPhee, Dale A.

AU - Verity, Erin

AU - Dyer, Wayne B.

AU - Wesselingh, Steven L.

AU - Learmont, Jennifer

AU - Sullivan, John S.

AU - Roche, Michael

AU - Zaunders, John J.

AU - Gabuzda, Dana

AU - Crowe, Suzanne M.

AU - Mills, John

AU - Lewin, Sharon R.

AU - Brew, Bruce J.

AU - Cunningham, Anthony L.

AU - Churchill, Melissa J.

PY - 2007/9/23

Y1 - 2007/9/23

N2 - In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection.

AB - In efforts to develop an effective vaccine, sterilizing immunity to primate lentiviruses has only been achieved by the use of live attenuated viruses carrying major deletions in nef and other accessory genes. Although live attenuated HIV vaccines are unlikely to be developed due to a myriad of safety concerns, opportunities exist to better understand the correlates of immune protection against HIV infection by studying rare cohorts of long-term survivors infected with attenuated, nef-deleted HIV strains such as the Sydney blood bank cohort (SBBC). Here, we review studies of viral evolution, pathogenicity, and immune responses to HIV infection in SBBC members. The studies show that potent, broadly neutralizing anti-HIV antibodies and robust CD8+ T-cell responses to HIV infection were not necessary for long-term control of HIV infection in a subset of SBBC members, and were not sufficient to prevent HIV sequence evolution, augmentation of pathogenicity and eventual progression of HIV infection in another subset. However, a persistent T-helper proliferative response to HIV p24 antigen was associated with long-term control of infection. Together, these results underscore the importance of the host in the eventual outcome of infection. Thus, whilst generating an effective antibody and CD8+ T-cell response are an essential component of vaccines aimed at preventing primary HIV infection, T-helper responses may be important in the generation of an effective therapeutic vaccine aimed at blunting chronic HIV infection.

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U2 - 10.1186/1742-4690-4-66

DO - 10.1186/1742-4690-4-66

M3 - Review article

VL - 4

JO - Retrovirology

T2 - Retrovirology

JF - Retrovirology

SN - 1742-4690

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ER -