Safety and Immunogenicity of Three Doses of a Five-Valent Pneumococcal Conjugate Vaccine in Children Younger Than Two Years With and Without Human Immunodeficiency Virus Infection

Abstract

Objective. To assess the safety and immunogenicity of three doses of a five-valent (types 6B, 23F, 14, 18C, and 19F) pneumococcal conjugate vaccine (PCV) among children younger than 2 years who are and are not infected with human immunodeficiency virus (HIV). Methods. A convenience sample of 18 HIV-infected children 2 years and younger (mean, 12.9 months) received three doses (each separated by 2 months) of PCV. An additional convenience sample of 33 non–HIV-infected children of virtually identical age, race, and sex as the HIV-infected group were randomized in a double-blind fashion to receive three doses of PCV or saline placebo. Safety data were collected for 72 hours after each vaccination. Sera were obtained before each and 1 month after the third vaccination to determine vaccine type-specific immunoglobulin G pneumococcal antibody titers by an enzyme-linked immunosorbent assay. Results. Seventeen HIV- and 30 non–HIV-infected children completed the study. The PCV was well tolerated by both HIV- and non–HIV-infected children. No significant differences in local or systemic reactions were noted between HIV- and non–HIV-infected PCV or placebo recipients. Three doses of PCV were immunogenic, as evidenced by 16- to 659-fold increases in type-specific geometric mean antibody titers over prevaccination levels in HIV- and non–HIV-infected children. With respect to an arbitrary protective level, 78% of the antibody titers from HIV-infected children and 88% of the titers from non–HIV-infected children were 1.0 μg/mL or greater 1 month after the third PCV dose. HIV-infected children with milder disease (Centers for Disease Control and Prevention classes N1–2, A1–2, and B1) were more likely to have protective antibody titers after the first and second PCV doses than HIV-infected children with more advanced disease (Centers for Disease Control and Prevention classes N3, A3, B2–3, and C1–3). However, after the third PCV dose, these differences disappeared. Conclusion. Three doses of PCV seem safe and immunogenic in both HIV- and non–HIV-infected children younger than 2 years. This type of vaccine should result in a marked reduction in systemic pneumococcal disease in both HIV- and non–HIV-infected children. Given the high incidence of invasive pneumococcal disease in HIV-infected children, this vaccine may markedly improve the quality of life for this unfortunate group of children.