Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.

BACKGROUND: Pneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown. METHODS: In a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease. RESULTS: In the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-to-treat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, -5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group. CONCLUSIONS: Among older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccine-type invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.).

Lower immunoglobulin G antibody responses to pneumococcal conjugate vaccination at the age of 2 years after previous nasopharyngeal carriage of Streptococcus pneumoniae.

OBJECTIVE: To determine whether nasopharyngeal pneumococcal carriage with serotypes 6B, 19F, or 23F interferes with immunoglobulin G (IgG) antibody responses to vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) at the age 24 months. STUDY DESIGN: Blood samples were collected before and after a PCV7 challenge vaccination at age 24 months from subsets of children participating in a randomized controlled trial. Children previously had received two doses of PCV7 at 2 and 4 months, two plus one doses of PCV7 at 2, 4, and 11 months, or no dosage until 24 months. Nasopharyngeal swabs were cultured at for Streptococcus pneumoniae at age 6 weeks and at 6, 12, 18, and 24 months. IgG responses were determined with enzyme immunoassay. RESULTS: Lower IgG responses against serotypes 6B, 19F, and 23F were observed on PCV7 challenge vaccination at 24 months in children who had received earlier PCV7 vaccinations and had been found positive for homologous carriage compared with non-carriers of these serotypes. Lower non-homologous IgG responses were observed after the PCV7 challenge at 24 months against serotype 6B after earlier 19F carriage and against serotype 19F after earlier 23F carriage compared with children who had not been positive for carriage of these serotypes. CONCLUSIONS: Pneumococcal colonization with serotypes 6B, 19F, and 23F is associated with diminished immune responses against these serotypes on PCV7 vaccination at 2 years of age. Underlying mechanisms deserve further investigation.

Effects of influenza plus pneumococcal conjugate vaccination versus influenza vaccination alone in preventing respiratory tract infections in children: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of influenza vaccination with or without heptavalent pneumococcal conjugate vaccination on respiratory tract infections (RTIs) in children. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled trial comprising 579 children age 18 to 72 months with a previous history of physician-diagnosed RTI, recruited between 2003 and 2005. The children were assigned to 2 doses of parenteral inactivated trivalent subunit influenza plus heptavalent pneumococcal conjugate vaccination (TIV+PCV7), influenza plus placebo vaccination (TIV+plac), or control hepatitis B virus vaccination plus placebo (HBV+plac). Main outcome measures were febrile RTI and related polymerase chain reaction (PCR)-confirmed influenza, primary care visits, antibiotic prescriptions, and acute otitis media (AOM) episodes. RESULTS: During influenza seasons, febrile RTI were reduced by 24% (95% confidence interval [CI] = 1% to 42%) in the TIV+PCV7 group and by 13% (95% CI = -12% to 32%) in the TIV+plac group compared with the control group. The occurrence of PCR-confirmed influenza was reduced by 52% (95% CI = 7% to 75%) in the TIV+PCV7 group and by 51% (95% CI = 3% to 75%) in the TIV+plac group. Episodes of AOM were reduced by 57% (95% CI = 6% to 80%) in the TIV+PCV7 group and by 71% (95% CI = 30% to 88%) in the TIV+plac group. Outside of the influenza seasons, no significant effects of vaccinations were demonstrated on the studied outcomes. CONCLUSIONS: During influenza seasons, influenza vaccination with or without pneumococcal conjugate vaccination substantially reduced cases of confirmed influenza and AOM episodes.