Immunogenicity of rotavirus vaccine (Rotarix) in infants with environmental enteric dysfunction


Innocent Mwape, Samuel Bosomprah, John Mwaba, Katayi Mwila-Kazimbaya, Natasha Makabilo Laban, Caroline Cleopatra Chisenga, Gibson Sijumbila, Michelo Simuyandi, Roma Chilengi



Deployment of rotavirus vaccines has contributed to significant declines in diarrheal morbidity
and mortality globally. Unfortunately, vaccine performance in low-middle income countries
(LMICs) is generally lower than in developed countries. The cause for this has been
associated with several host and maternal factors including poor water sanitation and
hygiene (WASH) status, which are predominant in LMICs. More recently, environmental
enteric dysfunction (EED) has specifically been hypothesized to contribute to poor vaccine
uptake and response. The aim of this study was to examine the association between serological
biomarkers of EED and seroconversion to rotavirus vaccine in Zambian infants.

This was a retrospective cohort study of 142 infants who had been fully immunized with
Rotarix™, and had known seroconversion status. Seroconversion was defined as 4-fold or
more increase in rotavirus-specific IgA titres between pre-vaccination and one month postdose
two vaccination. We performed ELISA assays to assess soluble CD14 (sCD14), Endotoxin
Core IgG Antibodies (EndoCAb), intestinal fatty acid binding protein (i-FABP) and
Zonulin according to the manufacturers protocols. Generalised linear model with familypoisson,
link-log and robust standard error was used to estimate the independent effects of
biomarkers on seroconversion adjusting for important cofounders.

The median concentration of Zonulin, Soluble CD14, EndoCaB, and IFABP were 209.3
(IQR = 39.7, 395.1), 21.5 (IQR = 21.5, 21.5), 0.3 (IQR = 0.3, 0.3), and 107.7 (IQR = 6.4,
1141.4) respectively. In multivariable analyses adjusting for the independent effect of other
biomarkers and confounders (i.e. age of child at vaccination, breast-milk anti-rotavirus IgA, infant serum anti-rotavirus IgG, and IgA seropositivity at baseline), there was strong evidence
of about 24% increase in seroconversion due to doubling Zonulin concentration
(Adjusted risk ratio (aRR) = 1.24; 95% CI = 1.12 to1.37; p<0.0001). Similarly, we found
about 7% increase in seroconversion due to doubling IFABP concentration (aRR = 1.07;
95% CI = 1.02 to 1.13; p = 0.006).

We found that high levels of zonulin and IFABP played a role in seroconversion. It is plausible
that increased gut permeability in EED allows greater uptake of the live virus within the
vaccine, but later consequences result in deleterious local structural distortions and malabsorption

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