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Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children
Authors:Sigurveig Th Sigurdardottir  Kimberly J Center  Katrin Davidsdottir  Vilhjalmur A Arason  Bjorn Hjalmarsson  Ragnheidur Elisdottir  Gunnhildur Ingolfsdottir  Robert Northington  Daniel A Scott  Ingileif Jonsdottir
Institution:1. Department of Immunology, Landspitali, The National University Hospital of Iceland, Hringbraut, 101 Reykjavik, Iceland;2. Faculty of Medicine, University of Iceland, Reykjavik, Iceland;3. Pfizer Inc., 500 Arcola Road, Collegeville, PA 19426, USA;4. Pfizer Inc., 401 North Middletown Road, Pearl River, NY 10965 USA;5. Centre for Child Health Services, The Primary Health Care of the Reykjavik Capital Area, Alfabakka 16, 109 Reykjavik, Iceland
Abstract:

Background

Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

Objective

To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal–meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

Methods

Children (n = 89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002–2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n = 50) and PCV9/PCV13 (n = 39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

Results

One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35 μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

Conclusions

PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.
Keywords:Antibody persistence  Conjugate vaccine  Hyporesponsiveness  Memory  Pneumococcus  Polysaccharide
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