Genetic Diversity of Human Rotavirus A Among Hospitalized Children Under-5 Years in Lebanon

Abstract

Human rotavirus remains a major cause of gastroenteritis worldwide despite the availability of effective vaccines. In this study, we investigated the genetic diversity of rotaviruses circulating in Lebanon. We genetically characterized the VP4 and VP7 genes encoding the outer capsid proteins of 132 rotavirus-associated gastroenteritis specimens, previously identified in hospitalized children (<5 years) from 2011 to 2013 in Lebanon. These included 43 vaccine-breakthrough specimens and the remainder were from non-vaccinated subjects. Phylogenetic analysis of VP4 and VP7 genes revealed distinct clustering compared to the vaccine strains, and several substitutions were identified in the antigenic epitopes of Lebanese specimens. No unique changes were identified in the breakthrough specimens compared to non-breakthroughs that could explain the occurrence of infection in vaccinated children. Further, we report the emergence of a rare P[8] OP354-like strain with a G9 VP7 in Lebanon, possessing high genetic variability in their VP4 compared to vaccine strains. Therefore, human rotavirus strains circulating in Lebanon and globally have accumulated numerous substitutions in their antigenic sites compared to those currently used in the licensed vaccines. The successful spread and continued genetic drift of these strains over time might undermine the effectiveness of the vaccines. The effect of such changes in the antigenic sites on vaccine efficacy remains to be assessed.

Comparative Analysis of G1P[8] Rotaviruses Identified Prior to Vaccine Implementation in Pakistan With Rotarix™ and RotaTeq™ Vaccine Strains

“…As rotavirus is continually altering its genetic makeup, it is therefore imperative to study how immunity derived from vaccines influences the development and spread of the vaccine-targeted major RVA strains ( 25 ). Vaccines that fail to eliminate a viral pathogen can apply pressures that cause changes in a microbial population’s genetic composition ( 26 ).…”

Prevalence, Pattern and Genetic Diversity of Rotaviruses among Children under 5 Years of Age with Acute Gastroenteritis in South Africa: A Systematic Review and Meta-Analysis

“…Similarly, a significant proportion of diarrheal episodes were consistently noted in an association with the heterotypic G2P [4] rotavirus genotype in Latin America, Belgium, Botswana, and Australia [87,[95][96][97] and G9P [8] in northern Vietnam [98], despite reports of large-scale vaccination with the Rotarix vaccine. While some authors have attributed changing aspects of genotype distribution to lack of sufficient protections against heterologous and the newly emerging rotavirus strains, creating opportunities for strain selection due to vaccine-induced immunological pressures [87,99], others are of the opinion that natural strain fluctuation or gene reassortment events would be more likely to influence the emergence and the epidemiological fitness of variants in the absence of limited herd immunity [22,100]. Although the rotavirus vaccine has been shown to offer both homotypic and heterotypic immunity [101], a reduction in the level of vaccine protection against the emerging dominant non-G1 strains (G2, G9, and G12) circulating among South African children is a possibility, as low vaccine effectiveness of 62% against strains with the G or P in the vaccine formulation and 52% against strains without a G or P in the vaccine formulation has been previously observed in South Africa [78].…”

“…To date, 36 different G genotypes and 51 different P genotypes have been described by RT-PCR and sequencing techniques [17]. Six G/P combinations: G1P [8], G2P [4], G3P [8], G4P [8], G9P [8], and G12P [8] or G9P [8] are the most prevalent combinations detected in humans globally [18][19][20][21][22][23][24]. Previously, uncommon rotavirus genotypes such as G1P [4], G2P [8], G9P [4], G12P [4], G8P [6], G8P [8], and G12P [6] have in recent times acquired epidemiological relevance on the African continent [13,25] and increased strain surveillance is needed to monitor the prevalence and potential changes of the dominant G and P types circulating in a given region.…”

Novel antigen panel for modern broad-spectrum recombinant rotavirus A vaccine

“…In addition, African strains with the P[6] genotype represented one-third of all strains identified [ 19 ]. After the mass introduction of vaccines in various countries, there was the replacement of previously widespread RVA strains with new ones (including rare genotypes), an increase in the diversity of genotypes, and an increase in the number of mutations in the antigenic determinants of the VP4 and VP7 proteins of strains in circulation compared to vaccine strains [ 20 21 22 23 ]. The lower efficacy of vaccines against emerging RVA strains has been reported [ 20 ].…”