Pathogenicity and immunogenicity of attenuated, nef-deleted HIV-1 strains in vivo.
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.
Gorry
Paul R
PR
Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia. gorry@burnet.edu.au
McPhee
Dale A
DA
Verity
Erin
E
Dyer
Wayne B
WB
Wesselingh
Steven L
SL
Learmont
Jennifer
J
Sullivan
John S
JS
Roche
Michael
M
Zaunders
John J
JJ
Gabuzda
Dana
D
Crowe
Suzanne M
SM
Mills
John
J
Lewin
Sharon R
SR
Brew
Bruce J
BJ
Cunningham
Anthony L
AL
Churchill
Melissa J
MJ
D015331:Cohort Studies; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D016325:HIV Long Terminal Repeat; D020276:HIV Long-Term Survivors / Q000706:statistics & numerical data; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D017384:Sequence Deletion; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000172:deficiency* / Q000235:genetics / Q000276:immunology
D054311:nef Gene Products, Human Immunodeficiency Virus