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333 Mucosal and Systemic HIV-Specific Immunity in HIV-Exposed but Uninfected Heterosexual Males
D. Trabattoni*1, S. Locaputo2, D. Luzzeri1, L. Lopalco3, F. Vichi2, C. Seletti1, F. Mazzotta2, and M. Clerici1
1Univ. of Milano, Italy; 2S.M. Annunziata Hosp., Firenze, Italy; and 3S. Raffaele Sci. Inst, Milano, Italy
Background: Despite multiple, repeated exposures to HIV, some individuals never seroconvert or shown any sign of infection. Mucosal and systemic immune correlates of protection have been analyzed in HIV-exposed women but no data are available in HIV-specific immune responses in exposed but uninfected heterosexual males
Methods: Cellular and humoral immune parameters were analysed in seminal fluid, urethral swabs, and PBMC of 12 heterosexual healthy men with repeated and recent (within 3 months and up to 1 day before the study) sexual exposure to HIV (ESN). Six HIV-infected individuals (HIV) and 6 healthy controls (HC) were also examined. Concomitant infectious or sexually transmitted diseases were not present in any of the individuals included in the study.
Results: HIV-specific IgA were detected in semen and urethral swabs of all ESN and HIV but not in HC (mean OD: ESN = 0.37; HIV = 0.51; HC = 0.11); IgG were present in HIV but neither in ESN nor in HC (mean OD: ESN = 0.007; HIV = 0.32; HC = 0.006). Neutralization of 2 HIV primary isolates was seen at high dilutions (1:270) with seminal fluid of 4/12 ESN and 4/6 HIV but was absent in HC. Seminal, but not peripheral, blood lymphocytes of ESN were enriched in activated populations (CD8+38+RO and CD4+25+). Strong env-, gag-, and pol-specific CTL were detected (ELIspot) in the peripheral blood of ESN (mean: env = 235; gag = 102; pol = 88 SFU/106 PBMC), CTL were weaker in HIV (mean: env = 80; gag = 55; pol = 42 SFU/106 PBMC) and absent in HC. Presence of mucosal and systemic HIV-specific immunity was not associated with HIV plasma viremia, CD4 counts, clinical stage, or presence/absence of antiviral therapy of the HIV-infected partner.
Conclusions:Exposure to HIV results in the activation of mucosal and systemic immune mechanisms in heterosexual males in whom infection cannot be detected by virological or clinical parameters. Because these ESN are uninfected despite continuous and repeated exposure, activation of HIV-specific humoral and cellular mucosal and systemic immunity is likely to be protective. These immune mechanisms should be reproduced in vaccine design.
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