Vaccination with 10-valent pneumococcal conjugate vaccine in infants according to HIV status

Abstract

Background: Phase III, open-label, single-center, controlled study in South Africa (ClinicalTrials.gov: NCT00829010) to evaluate immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) children.

Methods: Children stratified by HIV status received PHiD-CV primary vaccination (age 6/10/14 weeks; coadministered with routine childhood vaccines) and booster dose (age 9-10 months). Immune responses, assessed using enzyme-linked immunosorbent and functional assays, and safety were evaluated up to 14 months post-booster.

Results: Of 83, 101, and 100 children enrolled in HIV+, HEU, and HUU groups, 70, 91, and 93 were included in according-to-protocol immunogenicity cohort. For each vaccine-serotype, percentages of children with antibody concentrations ≥0.2 μg/mL were ≥97% 1 month post-primary vaccination and ≥98.5% 1 month post-booster (except for 6B and 23F at both timepoints). Post-primary vaccination, functional antibody responses were lower in HIV+ children: for each vaccine-serotype, percentages of children with opsonophagocytic activity (OPA) titres ≥8 were ≥72%, ≥81%, and ≥79% for HIV+, HEU, and HUU children. Post-booster, ≥87% of children in each group had OPA titres ≥8. Reactogenicity was similar across groups. Thirty one (37%) HIV+, 25 (25%) HEU, and 20 (20%) HUU children reported ≥1 serious adverse event. Five HIV+ and 4 HEU children died. One death (sudden infant death syndrome; HEU group; 3 days post-dose 1) was considered potentially vaccine-related.

Conclusion: PHiD-CV was immunogenic and well-tolerated in HIV+, HEU, and HUU children, and has the potential to provide substantial benefit irrespective of HIV infection status.

Conflict of interest statement

NF, JR-G, J-PY, MM, DB, and LS are employees of the GSK group of companies. JR-G, J-PY, MM, DB, and LS own shares of the GSK group of companies. Outside the submitted work, SAM declares his institution having received grants from Bill & Melinda Gates Foundation, the GSK group of companies, Novartis and Minervax. SAM has received consulting fees for advisory boards from the GSK group of companies, Medimmune, and Pfizer and payment for lectures including service on speakers bureaus from Sanofi Pasteur, the GSK group of companies, and Pfizer. SAM has also received payment from Medimmune for the development of educational presentations. All other authors declare no conflict of interest.

Figures

Figure 2

Participant flow of HIV-exposed and HIV-unexposed children vaccinated with 10-valent pneumococcal non-typeable H. influenzae protein D conjugate vaccine. ATP = according-to-protocol; N  = number of children; n = number with the characteristic; HEU = HIV-exposed-uninfected; HIV+ = HIV-infected; HUU = HIV-unexposed-uninfected; SAE = serious adverse event; TVC = total vaccinated cohort. ∗Only primary and first persistence analysis presented here. †Results presented elsewhere. Thirteen children with subject numbers were not vaccinated; they did not contribute to results.

Figure 3

Exploratory between-group comparisons of immunogenicity post-primary and post-booster vaccination (ATP immunogenicity cohort). Differences: HIV+ or HEU minus HUU; ratios: HIV+ or HEU divided by HUU. Post-primary, the HUU group consists of the pooled HUU (3+1/3+0) groups (panels A–D), and post-booster, the HUU group consists of the HUU (3+1) group (panels E–F). ATP = according-to-protocol; CI = confidence interval; GMC = geometric mean concentration; GMT = geometric mean titer; HEU = HIV-exposed-uninfected; HIV+ = HIV-infected; HUU = HIV-unexposed-uninfected; OPA = opsonophagocytic activity; PD = protein D.