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Serotype-specific immune unresponsiveness to pneumococcal conjugate vaccine following invasive pneumococcal disease

Ray Borrow1, Elaine Stanford, Pauline Waight

  • 1Vaccine Evaluation Unit, Health Protection Agency North West, Manchester Laboratory, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester M13 9XZ, United Kingdom. ray.borrow@hpa.org.uk

Infection and Immunity
|September 10, 2008
PubMed

Insights

Ten children showed inadequate antibody response to the pneumococcal 7-valent conjugate vaccine (PCV7), suggesting potential immune paralysis or genetic factors may affect vaccine effectiveness in preventing invasive pneumococcal disease (IPD).

Area of Science:

  • Immunology
  • Vaccinology
  • Pediatrics

Background:

  • The pneumococcal 7-valent conjugate vaccine (PCV7) was introduced into routine infant immunization in England, Wales, and Northern Ireland.
  • Pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered to children with invasive pneumococcal disease (IPD) to assess PCV7 response.
  • A protective antibody level was defined as a concentration of >= 0.35 microg/ml.

Purpose of the Study:

  • To evaluate the serotype-specific antibody response to PCV7 in children with invasive pneumococcal disease (IPD).
  • To identify potential factors contributing to vaccine non-responsiveness.

Main Methods:

  • Serum samples were collected from 107 children within 14 to 90 days of vaccination (one or more doses in the second year of life).
  • Samples were assayed using a multiplexed microsphere assay with cell wall polysaccharide and serotype 22F adsorption.
  • Serotype-specific antibody concentrations were measured to determine vaccine response.

Main Results:

  • Eight children failed to develop an adequate antibody response to their infecting serotype (6B, 18C, 4, 14) despite multiple PCV7 doses.
  • Two additional children were nonresponsive to a serotype (6B) different from their infecting serotype.
  • None of the 10 nonresponsive children had clinical risk factors for IPD; two had marginally low total IgG but responded to other PCV7 serotypes.

Conclusions:

  • Serotype-specific unresponsiveness to PCV7 was observed in a subset of children with IPD.
  • Potential causes include immune paralysis from high pneumococcal polysaccharide antigen loads.
  • A genetic predisposition to nonresponse to specific pneumococcal serotypes may also play a role.

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