Impact of maternal antibodies and microbiota development on the immunogenicity of oral rotavirus vaccine in African, Indian, and European infants

Edward P. K. Parker (), Christina Bronowski, Kulandaipalayam Natarajan C. Sindhu, Sudhir Babji, Blossom Benny, Noelia Carmona-Vicente, Nedson Chasweka, End Chinyama, Nigel A. Cunliffe, Queen Dube, Sidhartha Giri, Nicholas C. Grassly, Annai Gunasekaran, Deborah Howarth, Sushil Immanuel, Khuzwayo C. Jere, Beate Kampmann, Jenna Lowe, Jonathan Mandolo, Ira Praharaj, Bakthavatsalam Sandya Rani, Sophia Silas, Vivek Kumar Srinivasan, Mark Turner, Srinivasan Venugopal, Valsan Philip Verghese, Alistair C. Darby, Gagandeep Kang and Miren Iturriza-Gómara ()
Additional contact information
Edward P. K. Parker: London School of Hygiene and Tropical Medicine
Christina Bronowski: University of Liverpool
Kulandaipalayam Natarajan C. Sindhu: Christian Medical College
Sudhir Babji: Christian Medical College
Blossom Benny: Christian Medical College
Noelia Carmona-Vicente: University of Liverpool
Nedson Chasweka: University of Malawi
End Chinyama: University of Malawi
Nigel A. Cunliffe: University of Liverpool
Queen Dube: University of Malawi
Sidhartha Giri: Christian Medical College
Nicholas C. Grassly: Imperial College London
Annai Gunasekaran: Christian Medical College
Deborah Howarth: University of Liverpool
Sushil Immanuel: Christian Medical College
Khuzwayo C. Jere: University of Liverpool
Beate Kampmann: London School of Hygiene and Tropical Medicine
Jenna Lowe: University of Liverpool
Jonathan Mandolo: University of Malawi
Ira Praharaj: Christian Medical College
Bakthavatsalam Sandya Rani: Christian Medical College
Sophia Silas: Christian Medical College
Vivek Kumar Srinivasan: Christian Medical College
Mark Turner: University of Liverpool
Srinivasan Venugopal: Christian Medical College
Valsan Philip Verghese: Christian Medical College
Alistair C. Darby: University of Liverpool
Gagandeep Kang: Christian Medical College
Miren Iturriza-Gómara: University of Liverpool

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Identifying risk factors for impaired oral rotavirus vaccine (ORV) efficacy in low-income countries may lead to improvements in vaccine design and delivery. In this prospective cohort study, we measure maternal rotavirus antibodies, environmental enteric dysfunction (EED), and bacterial gut microbiota development among infants receiving two doses of Rotarix in India (n = 307), Malawi (n = 119), and the UK (n = 60), using standardised methods across cohorts. We observe ORV shedding and seroconversion rates to be significantly lower in Malawi and India than the UK. Maternal rotavirus-specific antibodies in serum and breastmilk are negatively correlated with ORV response in India and Malawi, mediated partly by a reduction in ORV shedding. In the UK, ORV shedding is not inhibited despite comparable maternal antibody levels to the other cohorts. In both India and Malawi, increased microbiota diversity is negatively correlated with ORV immunogenicity, suggesting that high early-life microbial exposure may contribute to impaired vaccine efficacy.

Date: 2021
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DOI: 10.1038/s41467-021-27074-1

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