Immunogenicity of ALVAC-HIV vCP1521 in infants of HIV-1-infected women in Uganda (HPTN 027): the first pediatric HIV vaccine trial in Africa

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00098163.

Conflict of interest statement

Potential conflict of interest: None declared

Figures

Figure 1

HPTN 027 CONSORT diagram. Flow chart showing patterns of women and infants from assessment of HIV infected women for eligibility to infant enrollment showing reasons for exclusion.

Figure 2

A. Representative plots of antigen-specific CD4+ T cells in a vaccine responder. PBMC were stimulated with Env peptides then stained with anti-IL2 PE, 4 anti-CD4 PerCP-Cy5.5, anti-CD3 AmCyan, and analyzed by flow cytometry. Samples were first gated on the CD3+/CD4+ lymphocyte population then the percent of IL-2 positive CD4+ T cells were determined. B. Representative Plot of Env-specific CD4 proliferation. CFSE-labeled PBMC were stimulated with ENV peptides for 5 days then assessed for proliferation by flow cytometry. Results are expressed as percent of proliferating CD8+ T-cells as measured by the extent of CFSE dilution. Positive proliferation is defined as >0·1% net and at least twice background. C. Representative plots of antigen-specific CD8+ T cells in a vaccine responder. PBMC were stimulated with Env peptides then stained with anti-CD107a PE, anti-IFN-γ FITC, anti-CD4 PerCP-Cy5.5, anti-CD3 AmCyan and anti-CD8 APC-Cy7, and analyzed by flow cytometry. Samples were first gated on the CD3+/CD8+ lymphocyte p opulation then the percent of CD107 and IFN-γ positive CD8+ T cells were determined.

Figures 3A & 3B

Single Point ELISA Optical Density readings by antigen type at each visit for participants in placebo arm (a) and vaccine arm (b). Qualitative (single-point titers) measurements of binding antibodies were determined from cryopreserved serum at weeks week 10, 14, month 6, 12, 18, 24). One dilution of serum at 1:50 dilution were tested in duplicate in microtiter plates coated with the following antigen: gp41 (subtype B), gp120MN (Subtype B, VaxGen), p24 (subtype B) and DP31–a synthetic AVERY peptide not present in the vaccine (AnaSpec Incorporated, San Jose, California, USA). An assay was considered positive if the antigen-specific optical density (OD) was ≥ 0.2, i.e., after subtraction of the OD of the no antigen plate