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AIDSVAX Immunization Induces HIV-specific CD8+ T Cell Responses in High-risk HIV- Volunteers Who Subsequently Acquire HIV Infection
Norman Jones*1, P Gilbert2, A DeCamp2, M Peterson3, M Gurwith3, and H Cao1
1California Dept of Hlth Svcs, Richmond, US; 2Fred Hutchinson Cancer Res Ctr, Seattle, WA, US; and 3Vaxgen, Inc, South San Francisco, CA, US
Background: VAX004, the first phase III efficacy
trial of an HIV vaccine, was a randomized, double-blinded, placebo-controlled
trial which was completed in 2003 without clear demonstration of effectiveness
in the reduction of either the acquisition of infection or level of plasma
viremia after HIV infection. The vaccine consisted of 300 µg each of rgp120 envelope
subunits derived from 2 subtype B isolates (AIDSVAX B/B; VaxGen). We evaluated
whether T cell responses can be elicited from VAX004 vaccine recipients.
Methods: Cryopreserved peripheral blood mononuclear
cells (PBMC) were randomly selected from placebo and vaccine recipients based
on behavioral risk factors documented at enrollment. Behavior risk score ranged
from 0 to 7; and was categorized as either low (0 to 2) or high (3 to 7). T
cell proliferation was measured by flow cytometry using carboxyfluorescein
diacetate, succinimidyl ester (CFSE) -labeled PBMC.
Results: Valid data were obtained for 149 samples.
CD8+ HIV-specific T cell proliferation was detected in 15 of 87
(17.2%) individuals who received the vaccine compared to 1 of 62 (1.6%) placebo
recipients. HIV-specific responses were more frequently detected among
vaccinees in the high-risk (n = 34) compared with low-risk (n = 53)
groups (26.5% and 11.3%, respectively), but did not reach statistical
significance (OR 2.82, p = 0.075). Surprisingly, the frequency of
responses was higher in vaccine recipients who subsequently acquired HIV
infection compared to individuals who remained HIV seronegative (34.8% and
10.9%, respectively, OR 4.34, p = 0.013). This difference remains
statistically significant after adjusting for risk score (OR 4.05, p = 0.020).
No difference in the frequency of human cytomegalovirus (HCMV) -specific
proliferation was observed among all subgroups (p> 0.05).
Conclusions: Our preliminary data indicate that
HIV-specific T cells can be induced in HIV-uninfected volunteers receiving
recombinant gp120 HIV vaccine in the VAX004 study. The immune response rate
appears to be highest in high-risk participants who would go on to contract HIV
infection. These results suggest that AIDSVAX may boost preexisting cellular
immune responses due to pre-infection exposure. However, vaccine-induced
enhancement of HIV infection cannot be ruled out.
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