Social Mixing with Other Children during Infancy Enhances Antibody Response to a Pneumococcal Conjugate Vaccine in Early Childhood

Abstract

Children who have siblings and/or who attend day care have higher rates of nasopharyngeal colonization with pneumococci than lone children do. Pneumococcal colonization is usually asymptomatic but is a prerequisite for invasive disease. We studied the effect of social mixing with other children on immunity to a pneumococcal vaccine. One hundred sixty children aged 1 year were immunized with a 7-valent conjugate pneumococcal vaccine. A blood sample was obtained before and 9 to 11 days after the vaccine. The concentration and avidity of antibody against vaccine pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were studied in relation to pneumococcal carriage rate and measures of social mixing. Children with increased social mixing had higher antibody concentrations against serotypes 4, 9V, 14, and 23F than lone children did. The least-carried serotype, serotype 4, was the one of the most immunogenic. This contrasts with serotype 6B, the most common nasopharyngeal isolate but the least immunogenic. Social mixing in infancy enhances the immune response to a Streptococcus pneumoniae polysaccharide-protein conjugate vaccine at 1 year of age. Exposure to pneumococci in the first year of life may induce immunological priming. An alternative explanation is that differences in immunological experience, such as increased exposure to respiratory viral infections in early childhood, alters the response to vaccines perhaps by affecting the balance between Th1 and Th2 cytokines. The low immunogenicity of serotype 6B polysaccharide might make conditions more favorable for carriage of the 6B organism and explain why 6B pneumococci were more frequently isolated than other serotypes.

Nasopharyngeal Carriage ofStreptococcus pneumoniaeShortly before Vaccination with a Pneumococcal Conjugate Vaccine Causes Serotype‐Specific Hyporesponsiveness in Early Infancy

“…In 1 study, the administration of 1 dose of PCV7 to 1-year-old toddlers resulted in significantly lower anti-9V antibody concentration 9-11 days after immunization in 8 children carrying S. pneumoniae serotype 9V at the time of immunization than in 152 children not carrying this serotype [39]. However, no significant differences were demonstrated for the other serotypes.…”

Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine

“…Serotype 4 induced the best IgA response following the primary immunization. This may be one reason for the low rates of detection of this serotype in carriage studies, and a lack of carriage in adults and toddlers may explain the similarity in response to this serotype following primary immunization (11,24,61,65).…”

“…Thus, the response to the primary dose of conjugate in this age group looks more like a naïve response than that seen in adults, even though the vaccine is conjugated. The absence of naturally acquired, polysaccharide-specific IgG B-cell memory in the toddlers prior to immunization might be related to a lack of priming via the nasopharyngeal carriage of pneumococci, except that a number of epidemiological studies have clearly shown that 80% of toddlers have carried the vaccine or vaccine-related serotypes of pneumococci by 1 year of age (10,36,40,61,65). These observations suggest that the amount of pneumococcal carriage experienced during the first year of life may not be sufficient to maintain the levels of IgG or the elevated frequencies of IgG memory B cells against all serotypes in this age group.…”

“…This is in contrast to the carriage data obtained for the same children, where serotype 23F was isolated frequently and serotype 4 was VOL. 15,2008 B-CELL RESPONSE TO A PNEUMOCOCCAL CONJUGATE VACCINE 189 never isolated (61). The responses of toddler B cells to the polysaccharides in the vaccine may be affected by the immunogenicity of the antigen.…”

The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies

“…69,70 Exposure to a greater number of serotypes also enhances immune responses. 71 In addition to anti-capsular antibodies, colonization in humans and in …”