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Clinical Trial
. 2024 Sep 19;16(9):1488.
doi: 10.3390/v16091488.

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi

Benjamin Morgan  1 , Eleanor A Lyons  1 , Amanda Handley  1   2 , Nada Bogdanovic-Sakran  1 , Daniel Pavlic  1 , Desiree Witte  3   4 , Jonathan Mandolo  3   5 , Ann Turner  4 , Khuzwayo C Jere  3   4 , Frances Justice  1 , Darren Suryawijaya Ong  1 , Rhian Bonnici  1 , Karen Boniface  1 , Celeste M Donato  1 , Ashley Mpakiza  3 , Anell Meyer  1   6 , Naor Bar-Zeev  4 , Miren Iturriza-Gomara  4   7 , Nigel A Cunliffe  4 , Margaret Danchin  1   7   8 , Julie E Bines  1   6   9
Affiliations
Clinical Trial

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi

Benjamin Morgan et al. Viruses. .

Abstract

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

Trial registration: ClinicalTrials.gov NCT03483116.

Keywords: RV3-BB vaccine; maternal antibodies; rotavirus vaccine.

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Conflict of interest statement

MCRI holds the patent for the RV3-BB vaccine: J.E.B., E.A.L., B.M., A.H., D.P., N.B.-S., R.B., D.S.O., F.J., and C.M.D. are/were employees of MCRI. C.M.D. has served on advisory boards for GSK (2019, 2021), with all payments directed to an administrative fund held by MCRI. N.C. is a National Institute for Health and Care Research (NIHR) Senior Investigator (NIHR 203756). N.C., A.T., and K.C.J. are affiliated with the NIHR Global Health Research Group on Gastrointestinal Infections at the University of Liverpool. N.C. and K.C.J. are affiliated with the NIHR Health Protection Research Unit in Gastrointestinal Infections at the University of Liverpool, a partnership with the UK Health Security Agency in collaboration with the University of Warwick. Views are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, the UK government, or the UK Health Security Agency.

Figures

Figure 1
Figure 1
Timing of administration of rotavirus vaccines in association with age-related changes in titres of maternal serum and breastmilk antibodies and infant serum IgG and IgA titres. Neonatal vaccine schedule (first dose at birth) (red arrows) with RV3-BB vaccine; infant vaccine schedule (first dose at 6–8 weeks of age) (black arrows): WHO-prequalified rotavirus vaccines (Rotarix®, RotaTeq®, Rotavac® (Bharat Biotech, Hyderabad, India) and Rotasiil® (Serum Institute of India, Pune, India) and RV3-BB vaccine administered in the infant schedule). Adapted from: Otero CE, Langel SN, Blasi M, Permar SR. PLoS Pathogens 2020 16(11):e1009010 [8].
Figure 2
Figure 2
Study design.
Figure 3
Figure 3
Infant participant flow for the Maternal Antibody study.
Figure 4
Figure 4
(a–c) Mean maternal rotavirus-specific serum IgA and IgG antibody titres (log transformed) in association with vaccine response in participants administered RV3-BB vaccine in the combined neonatal vaccine schedule group and the infant vaccine schedule group. The “y” axis denotes the serum maternal serum IgA and IgG antibodies titres (log). The “x” axis denotes the study groups according to neonatal or infant vaccine schedule group, per Investigation product (IP) dose, and according to vaccine response with the positive vaccine response variable (“Yes”) or negative vaccine response variable (“No”). Data are presented in a box-and-whisker plot, with the box extending from the 25th to the 75th percentile and the line in the middle plotted at the median. The whiskers represent the 10–90th percentiles, with all datapoints outside the 10–90th percentiles shown. Statistics and plotting were performed in Prism 9 for MacOs. Non-normally distributed data were analysed using the Mann–Whitney test. formula image Maternal rotavirus-specific serum IgA antibody titres (log). formula image Maternal rotavirus-specific serum IgG antibody titres (log).
Figure 5
Figure 5
Maternal rotavirus-specific serum IgA and IgG antibody titres are plotted against the anti-rotavirus serum IgA antibody titres of their infant after (a) the first dose (post vaccine dose 1) and (b) the full three-dose course (post vaccine dose 3) in each of the four treatment allocation groups. Separate linear regression models were used to explore the relationship between maternal rotavirus-specific serum IgA and IgG antibody titres (log transformed) against infant anti-rotavirus serum IgA antibody titre after vaccine dose 1 and dose 3. Statistical analyses were performed with Prism (GraphPad Software, Inc., version 10.0.1) by use of the unpaired Mann–Whitney test due to data not fitting the normal distribution. A p value of less than 0.05 was considered to be significant. 95% CI = 95% confidence interval. * = significant p < 0.05. ns = not significant p > 0.05. 1.0 × 106 neonate = low-titre neonatal vaccine schedule group. 3.0 × 106 neonate = mid-titre neonatal vaccine schedule group. 1.0 × 107 neonate = high-titre neonatal vaccine schedule group. 1.0 × 107 infant = infant vaccine schedule group.
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References

    1. Burke R.M., Tate J.E., Parashar U.D. Global experience with rotavirus vaccines. J. Infect. Dis. 2021;15:S792–S800. doi: 10.1093/infdis/jiab399. - DOI - PMC - PubMed
    1. International Vaccine Access Centre Vaccine Information Management System (VIMS) Global Rotavirus Vaccine Access Report. 2024. [(accessed on 18 July 2024)]. Available online: https://jhsph.edu/research/centers-and-institutes/ivac/view-hub.org/vacc....
    1. Black R.E., Perin J., Yeung D., Rajeev T., Miller J., Elwood S.E., Platts-Milss J.A. Estimated global and regional causes of deaths from diarrhea in childen younger that 5 years during 2002–21: A systematic review and Bayesian multinomial analysis. Lancet Glob. Health. 2024;12:e919–e928. doi: 10.1016/S2214-109X(24)00078-0. - DOI - PMC - PubMed
    1. Mehra R., Ray A., Das S., Chowdhury B.K., Koshal S.S., Hora R., Kumari A., Quadri S.F., Roy A.D. Enablers and barriers to rotavirus vaccine coverage in Assam, India–A qualitative study. Vaccine X. 2024;18:100479. doi: 10.1016/j.jvacx.2024.100479. - DOI - PMC - PubMed
    1. Lee B. Update on rotavirus vaccine underperformance in low-to-middle-income countries and next-generation vaccines. Hum. Vaccines Immunother. 2021;17:1787–1802. doi: 10.1080/21645515.2020.1844525. - DOI - PMC - PubMed

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