title: Strain characteristics of Streptococcus pneumoniae carriage and invasive disease isolates during a cluster-randomized clinical trial of the 7-valent pneumococcal conjugate vaccine.
abstract: Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has led to significant reductions in disease while changing pneumococcal population dynamics via herd immunity and serotype replacement. We performed multilocus sequence typing (MLST) on 590 pneumococcal isolates obtained during the American Indian clinical trial of PCV7, in which communities were randomized for eligible children to receive either PCV7 or a meningococcal conjugate vaccine (MCV). Sequence types (STs) were analyzed to determine the impact of the vaccine on pneumococcal population structure and to assess the possible impact of pneumococcal genetic background on vaccine effects. One hundred forty-three STs were obtained, the most frequent being ST199, the only one that included vaccine serotypes (VTs), non-vaccine-associated nonvaccine serotypes (NVA/NVTs), and vaccine-associated serotypes (VATs). Serotype replacement observed in the PCV communities was due to a diverse population of STs, most of which also existed in the MCV communities. Possible capsular switching to create novel ST associations with NVA/NVTs was detected only once. Reductions in VTs and changes in VATs in PCV communities did not show evidence of variation by ST, after accounting for lower vaccine effectiveness against serotype 19F. These observations suggest the hypothesis that the vaccine acts as a "serotype filter": its effect on a particular strain can be predicted on the basis of the serotype of the strain, with little effect of genetic background (as assessed by MLST) over and above capsule. If sustained, such patterns provide some cause for optimism that rapid evolution of PCV escape strains with drug resistance or high virulence is unlikely.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. mlipsitc@hsph.harvard.edu
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
authors.forename: Keith
authors.initials: K
authors.lastname: O'Neill
authors.forename: Derrick
authors.initials: D
authors.lastname: Cordy
authors.forename: Boris
authors.initials: B
authors.lastname: Bugalter
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Trzcinski
authors.forename: Claudette M
authors.initials: CM
authors.lastname: Thompson
authors.forename: Richard
authors.initials: R
authors.lastname: Goldstein
authors.forename: Stephen
authors.initials: S
authors.lastname: Pelton
authors.forename: Heather
authors.initials: H
authors.lastname: Huot
authors.forename: Valerie
authors.initials: V
authors.lastname: Bouchet
authors.forename: Raymond
authors.initials: R
authors.lastname: Reid
authors.forename: Mathuram
authors.initials: M
authors.lastname: Santosham
authors.forename: Katherine L
authors.initials: KL
authors.lastname: O'Brien
mesh_terms: D002353:Carrier State / Q000382:microbiology; D005838:Genotype; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D032521:Immunity, Herd; D007198:Indians, North American; D007223:Infant; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D009305:Nasopharynx / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000145:classification*; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics / Q000276:immunology; D018074:Vaccines, Conjugate / Q000627:therapeutic use
chemical_list: D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate