Natural Antibodies against Several Pneumococcal Virulence Proteins in Children during the Pre-Pneumococcal-Vaccine Era: the Generation R Study

Author:

Lebon Ankie123,Verkaik Nelianne J.3,Labout Joost A. M.12,de Vogel Corné P.3,Hooijkaas Herbert4,Verbrugh Henri A.3,van Wamel Willem J. B.3,Jaddoe Vincent W. V.125,Hofman Albert5,Hermans Peter W. M.6,Ma Jiangtao7,Mitchell Tim J.7,Moll Henriette A.2,van Belkum Alex3

Affiliation:

1. The Generation R Study Group, Erasmus MC, Rotterdam, Netherlands

2. Department of Pediatrics, Erasmus MC—Sophia Children's Hospital, Rotterdam, Netherlands

3. Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, Netherlands

4. Department of Immunology, Erasmus MC, Rotterdam, Netherlands

5. Department of Epidemiology, Erasmus MC, Rotterdam, Netherlands

6. Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

7. Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, Glasgow, United Kingdom

Abstract

ABSTRACT The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae . A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months ( n = 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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