Journal of Infectious Diseases
15 April 2009   Volume 199, Number 8
http://www.journals.uchicago.edu/toc/jid/current

EDITORIAL COMMENTARY
Prevention of Invasive Pneumococcal Disease in HIV-Infected Children: Expanding the Toolbox
Mark J. Abzug (1) and Stephen I. Pelton (2)
1University of Colorado Denver School of Medicine and The Children’s Hospital, Aurora; 2Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts

MAJOR ARTICLE
Quantitative and Qualitative Anamnestic Immune Responses to Pneumococcal Conjugate Vaccine in HIV-Infected and HIV–Uninfected Children 5 Years after Vaccination
Shabir A. Madhi,1,2; Keith P. Klugman,1,3; Locadiah Kuwanda,1,2; Clare Cutland,1,2; Helena Käyhty,3 and Peter Adrian1,2
Background.
Administration of pneumococcal conjugate vaccine (PCV) to HIV-infected children during infancy confers limited long-term protection in the absence of antiretroviral therapy. The objective of the present study was to determine the immune responses to PCV at 5 years of age in HIV-infected and HIV-uninfected children who had been primed with vaccine during infancy (i.e., previous vaccinees) and in those receiving their first dose of vaccine (i.e., control subjects).
Methods.
Serotype-specific antibodies were quantified by enzyme immunoassay, and antibody functionality to serotypes 6B, 9V, and 19F were evaluated using an opsonophagocytic killing assay 1 month after vaccination.
Results.
Of the HIV-infected children, 19.7% were receiving antiretroviral therapy, and 40.5% had a CD4+ cell percentage <15%. Geometric mean concentrations of antibody and the proportion with a concentration 0.35 μg/mL after vaccination were greater among HIV‐uninfected children than among HIV-infected children for both previous vaccinees and control subjects. Antibody concentrations after vaccination were lower for 3 of 7 serotypes among HIV-infected previous vaccinees than among control subjects. Detectable opsonophagocytic activity to all studied serotypes was lower among HIV-infected than among HIV‐uninfected previous vaccinees and control subjects. Postvaccination antibody‐mediated killing activity as determined by the opsonophagocytic killing assay was enhanced in control subjects compared with previous vaccinees among HIV‐uninfected children.
Conclusion.
HIV-infected vaccinees experience a partial loss of anamnestic responses to PCV. The optimal timing and frequency of booster vaccination as well as the responses to them among HIV-infected children need to be determined.

1Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand/Medical Research Council, and 2Vaccine Preventable Diseases, Department of Science and Technology/National Research Foundation, University of the Witwatersrand, Johannesburg, South Africa; 3Hubert Department of Global Health, Rollins School of Public Health and Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, Georgia; 4National Public Health Institute, Helsinki, Finland