Incidence of pneumococcal disease due to non-pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004.
ABSTRACT Widespread use of pneumococcal conjugate vaccine (PCV7) resulted in decreases in invasive disease among children and elderly persons. The benefits may be offset by increases in disease due to serotypes not included in the vaccine (hereafter, "nonvaccine serotypes"). We evaluated the effect of PCV7 on incidence of disease due to nonvaccine serotypes.
Cases of invasive disease were identified in 8 geographic areas through the Centers for Disease Control and Prevention's Active Bacterial Core surveillance. Serotyping and susceptibility testing of isolates were performed. We calculated the incidence of disease for children aged <5 years and adults aged > or =65 years. We compared rates of serotype-specific disease before and after PCV7 was licensed for use.
The annual incidence of disease due to nonvaccine serotypes increased from an average of 16.3 cases/100,000 population during prevaccine years (1998-1999) to 19.9 cases/100,000 population in 2004 for children aged <5 years (P=.01) and from 27.0 cases/100,000 population during prevaccine years to 29.8 cases/100,000 population in 2004 for adults aged > or =65 years (P=.05). Significant increases in the incidences of disease due to serotypes 3, 15, 19A, 22F, and 33F were observed among children during this period (P<.05 for each serotype); serotype 19A has become the predominant cause of invasive disease in children. The incidence of disease due to these serotypes also increased among elderly persons.
The incidence of pneumococcal disease caused by nonvaccine serotypes is increasing. Ongoing surveillance is needed to monitor the magnitude of disease caused by nonvaccine serotypes, to ensure that future vaccines target the appropriate serotypes.
[Show abstract] [Hide abstract]
ABSTRACT: Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) in children has led to significant reduction in pneumococcal disease in children and adults. However, diseases caused by serotypes not included in PCV7 have increased. A 15-valent pneumococcal conjugate vaccine (PCV15) containing serotypes in PCV7 and 8 additional serotypes (1, 3, 5, 6A, 7F, 19A, 22F, 33F) was developed and evaluated in toddlers 12 to 15 months of age. Ninety toddlers who completed an infant series with PCV7 received a single dose of either aluminum-adjuvanted PCV15, nonadjuvanted PCV15, or PCV7. Injection-site and systemic adverse events (AEs) were collected for 14 days postvaccination and serious AEs (SAEs) were collected for 30 days postvaccination. Solicited AEs included local (pain/tenderness, swelling, nodule and redness) and systemic (fatigue, arthralgia and myalgia) AEs. Serotype-specific immunoglobulin G (IgG) and opsonophagocytic (OPA) responses were measured immediately prior and 30 days postvaccination. Incidences of local and systemic AEs were comparable across vaccine groups. The majority of reported events, regardless of vaccine received, were transient and of mild to moderate intensity. No clinically significant differences were observed when comparing duration and severity of AEs. No vaccine-related SAEs or discontinuations from the study due to AEs were reported. Pneumococcal IgG concentrations and OPA titers increased postvaccination, with appreciable fold rises for all serotypes. Antibody levels were comparable between both PCV15 formulations and generally comparable to PCV7 for the shared serotypes. Both formulations of PCV15 display acceptable safety profiles and induce IgG and OPA responses to all vaccine serotypes.The Pediatric Infectious Disease Journal 02/2015; 34(2):186-194. DOI:10.1097/INF.0000000000000516 · 3.14 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Streptococcus pneumoniae (the pneumococcus) is a highly recombinogenic bacterium responsible for a high burden of human disease globally. Genetic recombination, a process in which exogenous DNA is acquired and incorporated into its genome, is a key evolutionary mechanism employed by the pneumococcus to rapidly adapt to selective pressures. The rate at which the pneumococcus acquires genetic variation through recombination is much higher than the rate at which the organism acquires variation through spontaneous mutations. This higher rate of variation allows the pneumococcus to circumvent the host innate and adaptive immune responses, escape clinical interventions, including antibiotic therapy and vaccine introduction. The rapid influx of whole genome sequence (WGS) data and the advent of novel analysis methods and powerful computational tools for population genetics and evolution studies has transformed our understanding of how genetic recombination drives pneumococcal adaptation and evolution. Here we discuss how genetic recombination has impacted upon the evolution of the pneumococcus.04/2015; 4. DOI:10.1016/j.csbj.2015.03.007
[Show abstract] [Hide abstract]
ABSTRACT: Streptococcus pneumoniae has proteins that are attached to its surface by binding to phosphorylcholine of teichoic and lipoteichoic acids. These proteins are known as choline-binding proteins (CBPs). CBPs are an interesting alternative for the development of a cost-effective vaccine and PspA (Pneumococcal surface protein A) is believed to be the most important protective component among the different CBPs. We sought to use CBPs eluted from pneumococci as an experimental vaccine. Since PspA shows variability between isolates, we constructed strains producing different PspAs. We used the non-encapsulated Rx1 strain, which produces PspA from clade 2 (PspA2), to generate a pspA-knockout strain (Rx1-ΔpspA) and strains expressing PspA from clade 1 (Rx1-pspA1) and clade 4 (Rx1-pspA4). We grew Rx1, Rx1-ΔpspA, Rx1-pspA1 and Rx1-pspA4 in Todd-Hewitt medium containing 0.5% yeast extract and washed cells in 2% choline chloride (CC). SDS-PAGE analysis of the proteins recovered by CC wash showed few bands, and the CBPs PspA and PspC (Pneumococcal surface protein C) were identified by MS analysis. Subcutaneous immunization of mice with these full-length native proteins without adjuvant led to significantly higher survival when compared to immunization with diluent after an intranasal lethal challenge with two pneumococcal strains and also against a colonization challenge with one strain. Importantly, immunization with recombinant PspA4 (rPspA4) without adjuvant did not elicit significant protection. Copyright © 2014, American Society for Microbiology. All Rights Reserved.Clinical and vaccine Immunology: CVI 12/2014; 22(2). DOI:10.1128/CVI.00692-14 · 2.37 Impact Factor