Objective: Maternal-to-child-transmission of HIV-1 infection remains a significant cause of HIV-1 infection despite successful prevention strategies. Testing protective HIV-1 vaccines remains a critical priority. The immunogenicity of ALVAC-HIV vCP1521 (ALVAC) in infants born to HIV-1–infected women in Uganda was evaluated in the first pediatric HIV-1 vaccine study in Africa.
Design: HIV Prevention Trials Network 027 was a randomized, double-blind, placebo-controlled phase I trial to evaluate the safety and immunogenicity of ALVAC in 60 infants born to HIV-1–infected mothers with CD4 counts of >500 cells per microliter, which were randomized to the ALVAC vaccine or placebo. ALVAC-HIV vCP1521 is an attenuated recombinant canarypox virus expressing HIV-1 clade E env, clade B gag, and protease gene products.
Methods: Infants were vaccinated at birth and 4, 8, and 12 weeks of age with ALVAC or placebo. Cellular and humoral immune responses were evaluated using interferon-γ enzyme-linked immunosorbent spot, carboxyfluorescein diacetate succinimidyl ester proliferation, intracellular cytokine staining, and binding and neutralizing antibody assays. Fisher exact test was used to compare positive responses between the study arms.
Results: Low levels of antigen-specific CD4 and CD8 T-cell responses (intracellular cytokine assay) were detected at 24 months (CD4—6/36 vaccine vs. 1/9 placebo; CD8—5/36 vaccine vs. 0/9 placebo) of age. There was a nonsignificant trend toward higher cellular immune response rates in vaccine recipients compared with placebo. There were minimal binding antibody responses and no neutralizing antibodies detected.
Conclusions: HIV-1–exposed infants are capable of generating low levels of cellular immune responses to ALVAC vaccine, similar to responses seen in adults.
*Medical Research Council/Uganda Virus Research Institute, Entebbe, Uganda;
†SCHARP, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
‡Viral and Rickettsial Disease Laboratory, Richmond, CA;
§Joint Clinical Research Center, Kampala, Uganda;
‖Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD;
¶Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda;
#Department of Paediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda;
**George Washington University School of Public Health and Health Services, Washington, DC;
††FHI 360, Durham, NC; and
‡‡Sanofi Pasteur, Discovery Drive, Swiftwater, PA.
Correspondence to: Pontiano Kaleebu, MBChB, PhD, MRC/UVRI Uganda Research Unit on AIDS, c/o Uganda Virus Research Institute, Plot 51-57 Nakiwogo Road, Entebbe, Uganda (e-mail: email@example.com).
The HIV Prevention Trials Network (HPTN) 027 study was funded by the U.S. National Institutes of Health (NIH), initially through the HPTN and later through the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group. The HPTN (U01AI46749) has been funded by the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institute of Drug Abuse (NIDA), and National Institute of Mental Health (NIMH). The IMPAACT Group (U01AI068632) has been funded by NIAID, NICHD, and NIMH. The study product was provided for free by Sanofi-Pastuer.
The authors have no conflicts of interest to disclose.
This study is registered with ClinicalTrials.gov, identifier NCT00098163.
Received September 05, 2013
Accepted September 05, 2013