Poster Presentation Lorne Infection and Immunity 2023

Cumulative vaccine take of RV3-BB rotavirus vaccine observed in Indonesian infants regardless of histo-blood group antigen status (#125)

Celeste M Donato 1 2 3 , Amanda Handley 1 4 , Sean G Byars 5 , Nada Bogdanovic-Sakran 1 , Eleanor Lyons 1 , Darren Suryawijaya Ong 1 , Daniel Pavlic 1 , Julie E Bines 1 2 6
  1. Enteric Diseases, Murdoch Children's Research Institute, Parkville, Victoria, Australia
  2. Department of Paediatrics, University of Melbourne, Parkville, Victoria , Australia
  3. Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia
  4. Medicines Development for Global Health, South Bank, VIC , Australia
  5. University of Melbourne, Parkville, VIC, Australia
  6. Department of Gastroenterology and Clinical Nutrition, Royal Children’s Hospital, Parkville, Victoria, Australia

Background: A disparity in vaccine effectiveness between high- and low-income settings has been observed for live-oral rotavirus vaccines administered to infants. Population differences in histo-blood group antigen (HBGA) status (determined by polymorphisms of the FUT2 and FUT3 genes) could be one factor contributing to this disparity due to human rotavirus strains binding to HBGAs in a strain dependent manner.

 

The RV3-BB rotavirus vaccine is comprised of a naturally attenuated human neonatal G3P[6] rotavirus strain. A phase IIb, randomized, double-blind, placebo-controlled trial of oral RV3-BB rotavirus vaccine was conducted in infants in Central Java and Yogyakarta, Indonesia. The aim of this study was to determine whether Lewis and secretor status impacted vaccine take.

 

Methods: Total DNA was extracted from infant stool samples (n= 164), the FUT2 and FUT3 genes amplified by PCR and sequenced on a NovaSeq SP Lane (Illumina). The single nucleotide polymorphisms (SNPs) identified in the FUT2 and FUT3 genes were analysed to infer the Lewis and secretor status of each participant. Cumulative vaccine take was defined as a serum immune response of anti-rotavirus immunoglobulin A (IgA) or serum neutralizing antibodies 28 days following dose administration or as detection of RV3-BB virus excretion in stool.

 

Results: Combined Lewis and secretor phenotype could be determined for 147/164 participants, with 94 designated as Lewis positive secretors, 1 designated as a Lewis positive non-secretor and 31 designated as Lewis positive weak secretors. A further 16 participants were designated as Lewis negative secretors and 5 were designated as Lewis negative weak secretors. Cumulative vaccine take was not significantly associated with either participant secretor status (RR=1.00, 95%CI=0.94-1.06, p=0.97) or Lewis phenotype (RR=1.03, 95%CI=0.94-1.14, p=0.33).

 

Conclusions: The G3P[6] human neonatal RV3-BB vaccine produced positive cumulative vaccine take, regardless of participant HBGA status in Indonesian infants.