A trial of a 9-valent pneumococcal conjugate vaccine in children with and those without HIV infection

BACKGROUND: Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa. METHODS: At 6, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo. All children received Haemophilus influenzae type b conjugate vaccine. Efficacy and safety were analyzed according to the intention-to-treat principle. RESULTS: Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and 3 among vaccine recipients). Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent (95 percent confidence interval, 19 to 88; 21 cases in the control group and 7 in the vaccinated group), and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent (95 percent confidence interval, 16 to 78; 32 and 14 cases, respectively). CONCLUSIONS: Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection.