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Safety and Immunogenicity of ALVAC-HIV vCP1521 in Infants Born to HIV-1-infected Women in Uganda (HPTN 027)
Norman Jones*1, D Sebikari2, I Ssewanyana3, L Baglyos4, S Zwerski5, M Swenson6, J Moye7, F Mmiro2, L Guay8, H Cao1, and HPTN027 Protocol Team
1California Dept of Publ Hlth, Richmond, US; 2Makerere Univ Johns Hopkins Univ Res Collaboration, Kampala, Uganda; 3Joint Clinical Res Ctr, Kampala, Uganda; 4Sanofi Pasteur, Swiftwater, PA, US; 5NIAID, NIH, Bethesda, MD, US; 6Statistical Ctr for HIV/AIDS Res and Prevention, Fred Hutchinson Cancer Res Ctr, Seattle, WA, US; 7Natl Inst of Child Hlth and Human Devt, NIH, Bethesda, MD, US; and 8Johns Hopkins Univ, Baltimore, MD, US
Background: HPTN 027, the first pediatric HIV
vaccine study in Africa, is a randomized, double-blind, placebo-controlled
trial of ALVAC-HIV vCP1521 in HIV exposed infants. vCP1521 is a live attenuated
recombinant canarypox virus expressing gene products from the HIV-1 clade E Env and clade B Gag. Primary trial objectives are to assess safety and immunogenicity of
vCP1521.
Methods: Infants born to HIV-infected, consenting
women receive vaccine/placebo (4:1) at birth, months 1, 2, and 3 with follow-up
for 24 months. Adverse events are monitored and graded using the 2004 DAIDS
toxicity classification. Cryopreserved peripheral blood mononuclear cells (PBMC)
from infants, collected at 10, 14, and 24 weeks, were tested using pooled peptides
corresponding to the HIV-1 Env gp120 and consensus clade B Gag. Flow
cytometry-based assays for vaccine-specific responses included expression of
surface CD107, intracellular cytokine production (interferon [IFN] -g
and interleukin [IL] -2) and cell proliferation (CFSE). Responses ≥0.1%
and 2 times the background were considered positive.
Results: We enrolled 60 infants from October 2006
until May 2007 in this ongoing blinded study. We gave 210 study vaccinations with
no severe or life-threatening reactogenicity events. By 24 September
2007, more than 99% of adverse events were either not related (461 of 630,
73.1%) or probably not related (167 of 630, 26.5%) to study product; 91.4% (576
of 630) were of mild or moderate severity, and included mainly infections or
lab abnormalities. Env-specific CD8+ T and CD4+ T
cell responses (as measured by CD107 expression or IFN-g and
Il-2 production) can be detected in HIV-uninfected infants vaccinated with
vCP1521 2 weeks after the third vaccination (3 of 48 and 7/48, respectively).
CD8+ and CD4+ T cell proliferation in response to Env peptides stimulation were
detectable in 9 of 38 and 9 of 32, respectively. In contrast, lower CD8+
or CD4+ response rates were observed against Gag peptides (1 of 48
and 2 of 48, respectively).
Conclusions: Our preliminary
blinded results indicate that vaccine-specific immune responses, CD4- and
CD8-mediated, can be elicited in infants born to HIV-infected mothers as early
as 10 weeks. The presence of proliferation and IL-2 production indicates that
vCP1521 induces memory T cell responses, which are a critical aspect of vaccine
design. There have been no safety concerns related to vaccine study product.
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