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
Posters
  • 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

    Disclosures:

    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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