A Trial of a 9-Valent Pneumococcal Conjugate Vaccine in Children with and Those without HIV Infection

TLDR

Streptococcus pneumoniae is a leading cause of morbidity and mortality from acute respiratory infections in young children. The study evaluated the efficacy of a 9‑valent pneumococcal conjugate vaccine in a randomized, double‑blind trial in Soweto, South Africa. The trial enrolled 39,836 infants who received either the 9‑valent conjugate vaccine (19,922) or placebo (19,914) at 6, 10, and 14 weeks, with all also receiving Haemophilus influenzae type b conjugate vaccine. The vaccine reduced invasive pneumococcal disease by 83% in HIV‑negative children and 65% in HIV‑positive children, lowered radiologically confirmed pneumonia by 20–25% in HIV‑negative infants, and cut penicillin‑ and trimethoprim‑sulfamethoxazole‑resistant invasive disease by 67% and 56%, respectively.

Abstract

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.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.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).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.