Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

Roma Chilengi, Michelo Simuyandi, Lauren Beach, Katayi Mwila, Sylvia Becker-Dreps, Devy M Emperador, Daniel E Velasquez, Samuel Bosomprah, Baoming Jiang, Roma Chilengi, Michelo Simuyandi, Lauren Beach, Katayi Mwila, Sylvia Becker-Dreps, Devy M Emperador, Daniel E Velasquez, Samuel Bosomprah, Baoming Jiang

Abstract

Introduction: Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).

Methods: 420 mother-child pairs were recruited at infant age 6-12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.

Results: Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68-0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).

Conclusion: Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Study Participants Flow chart.
Fig 1. Study Participants Flow chart.
Fig 2. Cumulative frequency profiles of RV-IgA…
Fig 2. Cumulative frequency profiles of RV-IgA titres in pre dose 1 breastmilk of 216 mother-infant pairs by infant IgA seroconversion post dose 2 of rotavirus vaccine.
Seroconversion was defined as four-fold increase in rotavirus-specific IgA titres in post dose 2 sera when compared to the corresponding pre-immunization sera.

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Source: PubMed

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