RESUMO
Immunological evaluation of the clinical impact of vaccines designed to protect against infection by Streptococcus pneumoniae requires measurement of serotype-specific functional antibodies. We describe the development and validation of a viable pneumococcal opsonophagocytosis assay (OPA) that can be used for routine serological analysis of paediatric immune responses after immunization. OPA seropositivity (%> or =8 threshold) reflected well invasive pneumococcal disease (IPD) effectiveness. In contrast, the 22F inhibition ELISA seropositivity (%> or =0.20microg/ml threshold) overestimated (19F) or underestimated (6B, 23F, 6A) IPD effectiveness for several serotypes. The seropositivity as estimated by a standardized and highly reproducible OPA was predictive for the serotype-specific IPD efficacy of pneumococcal conjugate vaccines.
Assuntos
Vacinas Meningocócicas/imunologia , Proteínas Opsonizantes/sangue , Fagocitose/imunologia , Vacinas Pneumocócicas/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática/métodos , Células HL-60 , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Vacinas Meningocócicas/uso terapêutico , Infecções Pneumocócicas/imunologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Streptococcus pneumoniae/imunologiaRESUMO
Diphtheria-tetanus-pertussis (DTP) combination vaccines based on inactivated whole-cell Bordetella pertussis (DTPw) or purified acellular pertussis components (DTPa) facilitate vaccine administration and will allow further co-administration such as with pneumococcal conjugates. Safety and immunogenicity studies are needed to demonstrate non-inferiority between combinations and the separate vaccines. The immunological non-inferiority is based on threshold antibody levels that represent correlates of protection. However, in case of pertussis, correlates of protection have not been defined or accepted. We describe the clinical evaluation of DTPa- and DTPw-based combinations and demonstrate their immunological non-inferiority as compared to their separately administered licensed counterparts. With respect to antibody responses against pertussis, a number of evaluations (vaccine response rates and geometric mean concentrations (GMCs) for anti-PT, anti-FHA, anti-PRN or anti-BPT; reverse cumulative distribution curves) are described. We also demonstrate that the B. pertussis mouse lung clearance model is able to predict clinical efficacy of licensed DTPa and DTPw vaccines and represents a useful tool to evaluate new combination vaccines.
