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Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.

ABSTRACT: In developing countries, introduction of pneumococcal conjugate vaccine has not eliminated circulation of vaccine serotypes. Vaccinating pregnant mothers to increase antibody concentrations in their newborn infants may reduce the acquisition of pneumococcal carriage and subsequent risk of disease. We explored the efficacy of passive immunity, attributable to anti-protein and anticapsular pneumococcal antibodies, against acquisition of carriage.We examined the rate of nasopharyngeal acquisition of pneumococci in the first 90 days of life associated with varying anticapsular and anti-protein antibody concentrations in infant cord/maternal venous blood in Kilifi, Kenya. We used multivariable Cox proportional hazard models to estimate continuous functions relating acquisition of nasopharyngeal carriage to the concentration of maternally derived antibody.Cord blood or maternal venous samples were collected from 976 mother-infant pairs. Pneumococci were acquired 561 times during 33,905 person-days of follow-up. Increasing concentrations of anti-protein antibodies were associated with either a reduction (PhtD1, PspAFam2, Spr0096, StkP) or, paradoxically, an increase (CbpA, LytC, PcpA, PiaA, PspAFam1, RrgBT4) in acquisition rate. We observed a nonsignificant reduction in the incidence of homologous carriage acquisition with high concentrations of maternally derived anticapsular antibodies to 5 serotypes (6A, 6B, 14, 19F, and 23F).The protective efficacy of several anti-protein antibodies supports the strategy of maternal vaccination to protect young infants from carriage and invasive disease. We were not able to demonstrate that passive anticapsular antibodies were protective against carriage acquisition at naturally occurring concentrations though it remains possible they may do so at the higher concentrations elicited by vaccination.

SUBMITTER: Ojal J

PROVIDER: S-EPMC5850545 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.

Ojal John J Goldblatt David D Tigoi Caroline C Scott J Anthony G JAG

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20180101 1

<h4>Background</h4>In developing countries, introduction of pneumococcal conjugate vaccine has not eliminated circulation of vaccine serotypes. Vaccinating pregnant mothers to increase antibody concentrations in their newborn infants may reduce the acquisition of pneumococcal carriage and subsequent risk of disease. We explored the efficacy of passive immunity, attributable to anti-protein and anticapsular pneumococcal antibodies, against acquisition of carriage.<h4>Methods</h4>We examined the r ...[more]

PMID: 29020230

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Project description:BackgroundPrior studies have demonstrated hyporesponsiveness to pneumococcal conjugate vaccines (PCVs) when administered in the presence of homologous carriage. This may be substantially more important in Africa where carriage prevalence is high. Deriving a correlate of protection (CoP) for carriage is important in guiding the future use of extended PCVs as population control of pneumococcal disease by vaccination is now focused principally on its indirect effect. We therefore explored the complex relationship between existing carriage and vaccine responsiveness, and between serum IgG levels and risk of acquisition.MethodsWe undertook secondary analyses of data from two previously published clinical trials of the safety and immunogenicity of PCV in Kenya. We compared responses to vaccination between serotype-specific carriers and non-carriers at vaccination. We assessed the risk of carriage acquisition in relation to PCV-induced serum IgG levels using either a step- or continuous-risk function.ResultsFor newborns, the immune response among carriers was 51-82% lower than that among non-carriers, depending on serotype. Among toddlers, for serotypes 6B, 14 and 19F the post-vaccination response among carriers was lower by between 29 and 70%. The estimated CoP against acquisition ranged from 0.26 to 1.93?g/mL across serotypes, however, these thresholds could not be distinguished statistically from a model with constant probability of carriage independent of assay value.ConclusionWe have confirmed hyporesponsiveness in an equatorial African setting in both infants and toddlers. Population responses to vaccination are likely to improve with time as carriage prevalence of vaccine serotypes is reduced. We have not found clear correlates of protection against carriage acquisition among toddlers in this population. Assessing the potential of new vaccines through the use of CoP against carriage is still difficult as there are no clear-cut serotype specific correlates.

Project description:The currently used Streptococcus pneumoniae vaccines have had a significant impact on the pneumococcal diseases caused by the serotypes they cover. Their limitations have stimulated a search for alternate vaccines that will cover all serotypes, be affordable and effective in young children. Pneumococcal protein antigens are potential vaccine candidates that may meet some of the shortfalls of the current vaccines. Thus, this study aimed to determine the relationship between antibodies against pneumococcal protein antigens and nasopharyngeal carriage in infants.One hundred and twenty mother-infant pairs were enrolled into the study. They had nasopharyngeal swabs(NPS) taken at birth and every two weeks for the first eight weeks after delivery, and blood samples were obtained at birth and every four weeks for the first eight weeks after delivery. Nasopharyngeal carriage of S. pneumoniae was determined from the NPS and antibodies against the pneumococcal proteins CbpA, PspA and rPly were measured in the blood samples.The S. pneumoniae carriage rate in infants increased to that of mothers by eight weeks of age. The odds of carriage in infants was 6.2 times (95% CI: 2.0-18.9) higher when their mothers were also carriers. Bacterial density in infants was lower at birth compared to their mothers (p = 0.004), but increased with age and became higher than that of their mothers at weeks 4 (p = 0.009), 6 (p = 0.002) and 8 (p<0.0001). At birth, the infants' antibodies against CbpA, and rPly pneumococcal protein antigens were similar, but that of PspA was lower (p<0.0001), compared to their mothers. Higher antibody concentrations to CbpA [OR (95% CI): 0.49 (0.26-0.92, p = 0.03)], but not PspA and rPly, were associated with protection against carriage in the infants.Naturally induced antibodies against the three pneumococcal protein antigens were transferred from mother to child. The proportion of infants with nasopharyngeal carriage and the bacterial density of S. pneumoniae increased with age within the first eight weeks of life. Higher concentrations of antibodies against CbpA, but not PspA and rPly, were associated with reduced risk of nasopharyngeal carriage of S. pneumoniae in infants.

Dataset Information

Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.

Publications

Effect of Maternally Derived Anti-protein and Anticapsular IgG Antibodies on the Rate of Acquisition of Nasopharyngeal Carriage of Pneumococcus in Newborns.

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