Antigenica and Genetic Characterization of Identified Rotavirus Strains in Qatar In Response to Rotarix Vaccine Usage

Abstract

Aim: To identify genetic and antigenic variation in RV in response to vaccine usage. Methods: A total of 231 RV-positive fecal samples were collected from children suffering from AGE during three-year study period between June 2016 and June 2019. The age of the subjects ranged between 2 months and 14 years (median of 16 months). RV genotyping and neutralizing regions, which include both VP4 (P-type) and VP7 (G type), were amplified and sequenced. We characterized amino acid sequence variability and predicted antigenicity compared to the Rotarix vaccine strain. Phylogenetic analyses were performed using MEGA7.0. Fisher’s exact test was used to run the statistical analysis for the clinical and demographical characteristics of circulating strains. Results: RV infection was most common in children between 3-36 months of age. Among the RV-positive cases, 135 (59.3%) had been vaccinated using either of the RV vaccines available. The number of children vaccinated with one and two-dose was 53 (39.2%) and 82 (60.8%), respectively. The percentage reduction of disease in a vaccinated group of pediatrics compared to an unvaccinated group of pediatrics was 25%. Of these, 108 (78.2%) experienced diarrhea for less than three days, and only eight (6.7%) had diarrhea for more than five days. All vaccinated children showed mild to moderate dehydration except for ten children who were then treated with intravenous fluids. G3 strains were the most strains detected (40%) followed by G2 (17.7%), G4 (16.8%), G9 (15%), G1 (9%), and G8 (0.9%). The dominant RV strains during the study period were G3P[8] (30.8%), G2P[8] (12.3%), G4P[8] (11.7%) and G1P[8] (10.4%). Comparisons of the amino acid residues defining the VP7 and VP4 antigenic domains revealed several mismatches between G1P [8] strains and the G1 and P[8] strains contained in the currently licensed rotavirus vaccines Rotarix. Eighty percent (n=8) of the G1 genotype specimens harbored three amino acid substitutions (N94S, S123N, and M217T) in 7‐1a and 7‐2b antigenic sites in comparison to the Rotarix vaccine. The P[8] strains with G4 and G9 counterparts showed the highest degree of variation among all specimens with known G genotype. These viruses had 15 and 13 substitutions in their VP4 antigenic epitopes when compared with the P[8] component of the Rotarix vaccines. Conclusion: This study suggests genetic variability in G1 genotype specimens to escape the vaccine-derived immune response. It also identified the wide diversity of circulating RV genotypes in Qatar