title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: aMedical Research Council: Respiratory and Meningeal Pathogens Research Unit bDepartment of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa cNational Institute for Communicable Diseases: a Division of the National Health Laboratory Service, Johannesburg, South Africa dGSK, Wavre, Belgium.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
authors.forename: Anthonet
authors.initials: A
authors.lastname: Koen
authors.forename: Lisa
authors.initials: L
authors.lastname: Jose
authors.forename: Nadia
authors.initials: N
authors.lastname: van Niekerk
authors.forename: Peter V
authors.initials: PV
authors.lastname: Adrian
authors.forename: Clare
authors.initials: C
authors.lastname: Cutland
authors.forename: Nancy
authors.initials: N
authors.lastname: François
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Guiñazú
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Yarzabal
authors.forename: Marta
authors.initials: M
authors.lastname: Moreira
authors.forename: Dorota
authors.initials: D
authors.lastname: Borys
authors.forename: Lode
authors.initials: L
authors.lastname: Schuerman
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D015658:HIV Infections; D006801:Humans; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008074:Lipoproteins / Q000276:immunology; D011008:Pneumococcal Infections / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D013019:South Africa; D014611:Vaccination / Q000009:adverse effects; D018074:Vaccines, Conjugate / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: C586648:10-valent pneumococcal conjugate vaccine; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C067989:glpQ protein, Haemophilus influenzae