Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in Infants and Toddlers

Yeh, Sylvia H.; Gurtman, Alejandra; Hurley, David; Block, Stan L.; Schwartz, Richard H.; Patterson, Scott D.; Jansen, Kathrin U.; Love, Jack; Gruber, William C.; Emini, Emilio A.; Scott, Daniel A.

doi:10.1542/peds.2009-3027

Cited by 204 publications

(127 citation statements)

References 28 publications

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“…In the PCV7 group, a correlation between the IgG and OPA levels was observed for the PCV7 serotypes and cross-reacting serotype 6A but not for 19A or the other PCV13 additional serotypes (with the exception of serotypes 3 and 7F after the toddler dose, but the immune responses for these serotypes were very low). The correlation between the OPA and ELISA results has also been demonstrated in other studies (4,5). The degree of OPA-to-IgG correlation can be affected by the OPA assay type used, e.g., killing OPA assay versus uptake assay.…”

Section: Discussionsupporting

confidence: 64%

Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization

Juergens

Patterson

Trammel

et al. 2014

Clin Vaccine Immunol

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In a randomized double-blind trial in healthy Israeli infants in Israel who received the 13-valent or 7-valent pneumococcal conjugate vaccine (PCV13 or PCV7, respectively) at 2, 4, 6, and 12 months, PCV13 significantly reduced nasopharyngeal (NP) colonization of serotypes 1, 6A, 7F, 19A, cross-reacting 6C, and the common PCV7 serotype 19F, from ages 7 to 24 months. No differences were observed between the vaccine groups for serotype 3 or for the remaining common PCV7 serotypes. For serotype 5, too few events were observed to draw an inference. Generally consistent with these findings, PCV13 elicited significantly higher enzyme-linked immunosorbent assay ( W e previously reported a randomized double-blind trial involving 1,866 healthy infants in Israel, which assessed the effectiveness of the 13-valent and 7-valent pneumococcal conjugate vaccines (PCV13 and PCV7, respectively), administered at 2, 4, 6, and 12 months of age, in reducing nasopharyngeal (NP) colonization from ages 7 to 24 months, and we compared the immunogenicity of the two vaccines measured by enzyme-linked immunosorbent assay (ELISA) 1 month after the infant series and 1 month after the toddler dose (1). The impact on NP colonization was generally consistent with the higher immune responses elicited by PCV13 (PCV7 plus serotypes 1, 3, 5, 6A, 7F, and 19A) compared with those of PCV7 (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F), as measured by ELISA, in particular for serotypes 1, 6A, 7F, 19A, and 19F, for which immune responses were significantly higher and NP colonization was significantly lower in the PCV13 group. For serotype 5, there were too few acquisitions to draw inferences, and for serotype 3, which elicited the lowest IgG immune response, no impact on colonization was observed (1).To further assess immune responses and colonization, functional antibodies were measured by opsonophagocytic activity (OPA) assays in the remaining serum. A post hoc analysis was then performed to assess whether there is an association between anticapsular IgGbinding antibody responses measured by ELISA and the functional antibodies measured by OPA assays, in order to ascertain whether the transfer of inferred associations between IgG responses and NP colonization to OPA responses is appropriate. MATERIALS AND METHODSTrial design. This randomized double-blind trial was conducted in Israel by a single coordinating center overseeing activities at 11 clinical sites. The details of the study, including vaccine formulations, are described elsewhere (1). In brief, eligible subjects were randomly assigned at a 1:1 ratio to receive PCV13 or PCV7. PCV13 or PCV7 was administered at approximately 2, 4, and 6 months of age (infant series), as well as at 12 months of age (toddler dose), by intramuscular injection into the anterolateral left thigh. Other pediatric vaccines were administered according to national recommendations into the anterolateral right thigh. Blood samples for serology were obtained at 1 month after the infant series and at 1 month after the toddler dose...

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Section: Discussionsupporting

confidence: 64%

Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization

Juergens

Patterson

Trammel

et al. 2014

Clin Vaccine Immunol

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“…Indeed, despite an effectiveness of 26% (95% CI, Ϫ45% to 62%) as estimated by U.S. Centers for Disease Control and Prevention (41), the vaccine was not able to prevent the increase in 19A IPD (16,21,24). Previous studies by Pfizer, Inc. showed that over 80% of subjects vaccinated with three doses of 7vCRM had antibody concentrations against serotype 19A that reached the antibody threshold, whereas only approximately 17% of the subjects had functional antibodies when measured using the OPA assay (4,17,47). These and our results support the conclusion that a large fraction of the crossreactive antibodies induced by 7vCRM against serotype 19A are nonfunctional.…”

Section: Discussionmentioning

confidence: 96%

Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption

Schuerman

Wysocki

Tejedor

et al. 2011

Clin Vaccine Immunol

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We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (>0.2 g/ml) and OPA assay (titer, >8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of >0.2 g/ml IgG and an OPA titer of >8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.

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“…Furthermore, recent epidemiological data suggested that the administration of PCV7 has led to increases in the colonization of the nasopharynx by S. aureus and nonvaccine strains of S. pneumoniae, which may contribute to vaccine-resistant OM and other infections (20,149). In spite of this, a PCV13 vaccine, containing additional antigens for six other common pneumococcal strains, has recently been cleared for use in the United States and several other countries (223). Initial studies have shown similar safety and efficacy in priming antibody responses to the same degree as the PCV7 vaccine; follow-up studies will further clarify the success of this current vaccine design in reducing overall invasive pneumococcal morbidity (157).…”

Section: Considerations For Design and Use Of Polymicrobial Vaccinesmentioning

confidence: 99%

Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

et al. 2012

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SUMMARY Microorganisms coexist in a complex milieu of bacteria, fungi, archaea, and viruses on or within the human body, often as multifaceted polymicrobial biofilm communities at mucosal sites and on abiotic surfaces. Only recently have we begun to appreciate the complicated biofilm phenotype during infection; moreover, even less is known about the interactions that occur between microorganisms during polymicrobial growth and their implications in human disease. Therefore, this review focuses on polymicrobial biofilm-mediated infections and examines the contribution of bacterial-bacterial, bacterial-fungal, and bacterial-viral interactions during human infection and potential strategies for protection against such diseases.

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Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in Infants and Toddlers

Abstract: PCV13 will be as effective as PCV7 in the prevention of pneumococcal disease caused by the 7 common serotypes and could provide expanded protection against the 6 additional serotypes. The PCV13 safety profile was comparable to that of PCV7.

Cited by 204 publications

References 28 publications

Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization

Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization

Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption

Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

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