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Clinical Trial
. 2011 Sep 16;29(40):6994-7001.
doi: 10.1016/j.vaccine.2011.07.035. Epub 2011 Jul 23.

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization

Shabir A Madhi  1 , Avy Violari, Keith P Klugman, Gina Lin, James A McIntyre, Anne von Gottberg, Patrick Jean-Philippe, Mark F Cotton, Peter Adrian; CIPRA 4 team
Collaborators, Affiliations
Clinical Trial

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization

Shabir A Madhi et al. Vaccine. .

Abstract

Background: Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.

Methods: We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses.

Results: Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ≥ 8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ≥ 8 than the effect of colonization on the lower proportion with antibody ≥ 0.35 μg/ml.

Conclusion: Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype.

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Figures

Figure 1
Figure 1
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 6B prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 6B only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
Figure 1
Figure 1
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 6B prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 6B only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
Figure 2
Figure 2
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 19F prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 19F only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
Figure 2
Figure 2
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 19F prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 19F only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
Figure 3
Figure 3
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 23F prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 23F only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
Figure 3
Figure 3
a-c: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for colonized versus not colonized with serotype 23F prior to first dose of PCV. d-f: Comparison of geometric mean antibody concentrations at baseline and one- and six months after three doses of pneumococcal conjugate vaccine (PCV) for infants colonized with serotype 23F only prior to the second and/or third dose of PCV versus those not colonized until the third PCV dose.
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