446. Serotype and Pathogen Replacement in Nasopharyngeal Carriage and Acute Otitis Media after Vaccination with Protein D-based Pneumococcal Conjugate Vaccines (PCVs)
Session: Poster Abstract Session: Pneumococcal Vaccine in Children and Adults
Thursday, October 3, 2013
Room: The Moscone Center: Poster Hall C
  • Hausdorff_IDWeek_Poster446_highres.pdf (2.1 MB)
  • Background: Double-blind randomized controlled trials (DBRCTs) have shown that the 7-valent pneumococcal CRM197-conjugate vaccine (7vCRM) reduces vaccine type (VT) nasopharyngeal carriage (NPC) and acute otitis media (AOM), but can simultaneously increase non-vaccine type (NVT) NPC and AOM, yielding reduced overall AOM but usually little or no net change in overall pneumococcal NPC. Some reports have also suggested a rise in AOM caused by non-typeable Haemophilus influenzae (NTHi) and in NPC of other pathogens. We assessed if such serotype and pathogen replacement occurred in NPC and AOM after vaccination with protein D-based PCVs.

    Methods: We evaluated vaccine impact on NVT and non-pneumococcal pathogen NPC and AOM in 3 DBRCTs (efficacy trials with non-active control): 2 with the 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV, GlaxoSmithKline Vaccines), in Finland (NCT00839254: NPC, N=5093) and Latin America (COMPAS, NCT00466947: NPC, N=1921; AOM, N=7214), and 1 with an investigational 11-valent formulation (11Pn-PD) in the Czech Republic and Slovakia (POET, NCT00119743: NPC, N=381; AOM, N=4968).

    Results: In the 3 DBRCTs, no increases in NVT NPC were observed until 3 months after PHiD-CV booster vaccination (Finnish study and COMPAS) or 12 months after 11Pn-PD booster vaccination (POET). These increases in the second year of life were generally smaller than the reductions in VT NPC seen at the same time points, resulting in a consistent trend for a net reduction in overall pneumococcal NPC throughout the second year of life. In COMPAS and POET (both assessing AOM etiology), PHiD-CV or 11Pn-PD vaccination substantially reduced the number of VT AOM episodes, with no apparent increase in NVT AOM. Despite inconsistent effects on NTHi NPC across the 3 studies, positive point estimates for vaccine efficacy against NTHi AOM were observed in POET and COMPAS. No change was observed for other pathogen NPC or AOM in the 3 DBRCTs.

    Conclusion: The DBRCTs to date did not provide evidence of replacement of VT by NVT or other pathogens in AOM after vaccination with protein-D based PCVs, and showed delayed, partial replacement of VT by NVT NPC, yielding a net decrease in overall pneumococcal carriage.

    Funding: GlaxoSmithKline Biologicals SA

    William P. Hausdorff, PhD, Christopher Clarke, PhD, Marta Moreira, MD, Tomas Mrkvan, PhD, Javier Ruiz Guiñazú, MD and Dorota Borys, MD, GlaxoSmithKline Vaccines, Wavre, Belgium


    W. P. Hausdorff, GlaxoSmithKline Vaccines: Employee and Shareholder, Salary

    C. Clarke, GlaxoSmithKline Vaccines: Employee, Salary

    M. Moreira, GSK Vaccines : Employee, Salary and Stocks from GSK Vaccines

    T. Mrkvan, GlaxoSmithKline Vaccines, registered as GlaxoSmithKline Biologicals, s.a.: Employee, . and Salary

    J. R. Guiñazú, GaloxSmithKline Vaccines: Employee and Shareholder, Salary

    D. Borys, GlaxoSmithKline Biologicals: Employee and Shareholder, Salary and shares and share options

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