Cross-reactive T cell responses in HIV CRF01_AE and B'-infected intravenous drug users: implications for superinfection and vaccines.
Abstract We previously observed limited cross-reactive T cell responses in two HIV-1-superinfected injection drug users (IDUs) before superinfection [Ramos A, et al.: J Virol 2002;76(15):7444-7452]. To elucidate the role of such responses in superinfection we examined cross-reactive T cell responses in IDUs infected with a single HIV-1 subtype. In this study, IFN-gamma ELISPOT assays were performed using recombinant vaccinia constructs and peripheral blood mononuclear cells (PBMCs) from 43 IDUs singly infected with CRF01_AE or B' from the same cohort as the superinfected IDUs. PBMCs were from time points corresponding to pre- (early) or post- (late) superinfection in the superinfected IDUs. We observed that most singly infected IDUs had cross-reactivity in samples from early (84% of CRF01_AE and 78% of B'-infected IDUs) and late (96% of CRF_01AE and 77% of B'-infected IDUs) time points. Frequent homologous reactivity at early (67% of CRF-01AE and 100% of B') and late (84% of CRF01_AE-infected and 100% of B'-infected IDUs) time points was also observed. Cross-reactive responses were predominantly to Pol and were broader and higher in CRF01_AE than in B'-infected IDUs (medians of 825 vs. 90 and 585 vs. 60 spot-forming units/10(6) PBMCs at early and late time points, respectively). Our results show that cross-reactive responses were more prevalent with greater height and breadth in singly infected IDUs than previously observed in corresponding collection time points of superinfected IDU. Thus, low or absent cross-reactivity may have contributed to the previously observed superinfections. These data are relevant for understanding superinfection and improving vaccine design.
Promadej-Lanier
Nattawan
N
Division of HIV/AIDS Prevention, National Center for HIV/AIDS, STD, TB, and Viral Hepatitis Prevention, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia 30333, USA. nlanier@cdc.gov
Thielen
Caroline
C
Hu
Dale J
DJ
Chaowanachan
Thanyanan
T
Gvetadze
Roman
R
Choopanya
Kachit
K
Vanichseni
Suphak
S
McNicholl
Janet M
JM
D000328:Adult; D002478:Cells, Cultured; D055030:Drug Users; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015819:Substance Abuse, Intravenous / Q000150:complications; D013601:T-Lymphocytes / Q000276:immunology*