Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 221, Issue 7, Pages 1070-1078Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz333
Keywords
Rotavirus; RV3-BB; histo-blood group antigens; neonatal vaccination; vaccine take; Lewis antibodies; secretor status
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Funding
- Australian National Health and Medical Research Council [ID491239]
- New Zealand Health Research Council International Investment Opportunities Fund Trans-Tasman Clinical Trials Collaborative Initiative [08_T02]
- Victorian Government's Operational Infrastructure Support Program
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Background. VP4 [P] genotype binding specificities of rotaviruses and differential expression of histo-blood group antigens (HBGAs) between populations may contribute to reduced efficacy against severe rotavirus disease. P[6]-based rotavirus vaccines could broaden protection in such settings, particularly in Africa, where the Lewis-negative phenotype and P[6] rotavirus strains are common. Methods. The association between HBGA status and G3P[6] rotavirus vaccine (RV3-BB) take was investigated in a phase 2A study of RV3-BB vaccine involving 46 individuals in Dunedin, New Zealand, during 2012-2014. FUT2 and FUT3 genotypes were determined from DNA extracted from stool specimens, and frequencies of positive cumulative vaccine take, defined as an RV3-BB serum immune response (either immunoglobulin A or serum neutralizing antibody) and/or stool excretion of the vaccine strain, stratified by HBGA status were determined. Results. RV3-BB produced positive cumulative vaccine take in 29 of 32 individuals (91%) who expressed a functional FUT2 enzyme (the secretor group), 13 of 13 (100%) who were FUT2 null (the nonsecretor group), and 1 of 1 with reduced FUT2 activity (i.e., a weak secretor); in 37 of 40 individuals (93%) who expressed a functional FUT3 enzyme (the Lewis-positive group) and 3 of 3 who were FUT3 null (the Lewis-negative group); and in 25 of 28 Lewis-positive secretors (89%), 12 of 12 Lewis-positive nonsecretors (100%), 2 of 2 Lewis-negative secretors, and 1 of 1 Lewis-negative weak secretor. Conclusions. RV3-BB produced positive cumulative vaccine take irrespective of HBGA status. RV3-BB has the potential to provide an improved level of protection in settings where P[6] rotavirus disease is endemic, irrespective of the HBGA profile of the population.
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