Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi

Abstract

The human, G1P [8] rotavirus vaccine (Rotarix) significantly reduced severe rotavirus gastroenteritis episodes in a clinical trial in South Africa and Malawi, but vaccine efficacy was lower in Malawi (49.5%) than reported in South Africa (76.9%) and elsewhere. The aim of this study was to examine the molecular relationships of circulating wild-type rotaviruses detected during the clinical trial in Malawi to RIX4414 (the strain contained in Rotarix) and to common human rotavirus strains. Of 88 rotavirus-positive, diarrhoeal stool specimens, 43 rotaviruses exhibited identifiable RNA migration patterns when examined by polyacrylamide gel electrophoresis. The genes encoding VP7, VP4, VP6 and NSP4 of 5 representative strains possessing genotypes G12P[6], G1P[8], G9P [8], and G8P[4] were sequenced. While their VP7 (G) and VP4 (P) genotype designations were confirmed, the VP6 (I) and NSP4 (E) genotypes were either I1E1 or I2E2, indicating that they were of human rotavirus origin. RNA-RNA hybridization using 21 culture-adapted strains showed that Malawian rotaviruses had a genomic RNA constellation common to either the Wa-like or DS-1 like human rotaviruses. Overall, the Malawi strains appear similar in their genetic make-up to rotaviruses described in countries where vaccine efficacy is greater, suggesting that the lower efficacy in Malawi is unlikely to be explained by the diversity of circulating strains.

Group A rotaviruses circulating prior to a national immunization programme in Nigeria: Clinical manifestations, high G12P[8] frequency, intra‐genotypic divergence of VP4 and VP7

“…Since its first detection in the Philippines in 1987, G12 strains have been detected in many parts of the world and may be regarded as the sixth most important human genotype . Furthermore, G12 strains have been found with high frequency in most of the recent African studies . Of note is the fact that all the G12 strains observed in this study were associated with P[8] exclusively.…”

“…[18][19][20] Furthermore, G12 strains have been found with high frequency in most of the recent African studies. 12,21,22 Of note is the fact that all the G12 strains observed in this study were associated with P[8] exclusively. Most African G12…”

Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa

“…In addition, the number of RV whole genomes reported from Africa still remains relatively low compared to whole genomes from other parts of the world (Dennis et al, 2014; Heylen et al, 2014; Jere et al, 2011, 2012, 2014; Magagula et al, 2015; Nakagomi et al, 2013; Nyaga et al, 2013, 2014). Such data would aid our understanding of viral factors that could possibly assist in understanding the lower immunogenicity and efficacy of RV vaccines observed in developing countries (Armah et al, 2010; Madhi et al, 2010; Nakagomi et al, 2012; Sow et al, 2012; Steele et al, 2012). …”

Multiplexed one-step RT-PCR VP7 and VP4 genotyping assays for rotaviruses using updated primers

“…Four hundred of these sequences were representatives of known lineages and sub-lineages of the five common VP4 genotypes (Donato et al, 2012; Magagula et al, 2014; Nakagomi et al, 2012; Nyaga et al, 2014), while 1400 were representatives of known lineages and sub-lineages of the six common VP7 genotypes (Donato et al, 2012; Esona et al, 2013; Magagula et al, 2014; Nakagomi et al, 2012; Nyaga et al, 2014; Stupka et al, 2009, 2012). The consensus sequences obtained from multiple alignments of the six most common RVA VP7 genotypes (G1, G2, G3, G4, G9 and G12) and five most common VP4 genotypes (P[4], P[6], P[8], P[9] and P[10]) were used to design oligonucleotide primers for specificVP7 and VP4 genotypes, respectively.…”