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Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

ABSTRACT: Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses.Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ? 8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ? 8 than the effect of colonization on the lower proportion with antibody ? 0.35 ?g/ml.Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype.

SUBMITTER: Madhi SA

PROVIDER: S-EPMC3167924 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

Madhi Shabir A SA Violari Avy A Klugman Keith P KP Lin Gina G McIntyre James A JA von Gottberg Anne A Jean-Philippe Patrick P Cotton Mark F MF Adrian Peter P

Vaccine 20110723 40

<h4>Background</h4>Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.<h4>Methods</h4>We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose ...[more]

PMID: 21787822

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Project description:BackgroundWe describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic-resistant pneumococci in urban Alaskan children during 2000-2010.MethodsWe obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90 days before enrollment were determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS.ResultsWe recruited 3496 children (median, 452 per year). During 2000-2010, a range of 18-29% per year of children used PCN/amoxicillin (P value for trend = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0[FIGURE DASH]90%; P < 0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53-<1%; P < 0.01) and non[FIGURE DASH]PCV7-serotype proportion increased (43-95%; P < 0.01). PCN-R pneumococcal colonization prevalence decreased (23-9%; P < 0.01) and PCN-I pneumococcal colonization prevalence increased (13-24%; P < 0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non[FIGURE DASH]PCV7-type pneumococci remained unchanged; a mean of 31% per year of PCV7-type and 10% per year of non[FIGURE DASH]PCV7-type isolates were PCN-R, and 10% per year of PCV7 and 20% per year of non[FIGURE DASH]PCV7-type isolates were PCN-I.ConclusionsOverall, PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype groups (PCV7 vs. non-PCV7) despite stable PCN use in our population.

Project description:Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites.

Project description:BackgroundReduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children.MethodsFrom 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses.ResultsReceiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months.ConclusionsOur results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

Dataset Information

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

Publications

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

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