4 million hospitalisations in children under five years of age [2

4 million hospitalisations in children under five years of age [2]. The mortality rates associated with rotavirus disease are unevenly distributed; of the estimated 527,000 annual rotavirus deaths, the overwhelming majority occur in developing nations in Asia and Sub-Saharan Africa [3]. Rotavirus belongs to the Reoviridae virus family and has an 11 segment double-stranded RNA (dsRNA) genome that encodes six structural viral PS-341 purchase proteins (VP1–4, VP6, VP7) and six non-structural proteins (NSP1–6). The RNA genome is encased in three concentric layers of protein consisting of a core, inner and outer capsid [4]. Rotavirus can be classified into seven

groups (Group A–G) based on the genetic characteristics and antigenicity of the inner capsid protein VP6. Group A rotaviruses are the most common cause of symptomatic disease in humans. The two outer capsid proteins VP7 and VP4 elicit type-specific and cross-reactive neutralising antibody responses, and are used to classify Group A rotavirus strains into G (glycoprotein, VP7) and P (protease sensitive, VP4)

genotypes, respectively [4] and [5]. Of the 24 G genotypes and 33 P genotypes described to date, 12 G and 15 P genotypes are known to infect humans [6] and [7]. Genotype G1P[8], G2P[4], G3P[8], G4P[8] and G9P[8] strains cause over 90% of rotavirus disease worldwide. In North America, Europe and Australia they represent over 90% of characterised isolates, but in South America and Africa they represent 83% and 55% of isolates respectively [8]. Genotype G9 strains were initially identified Epacadostat mw in the USA, and Japan in the 1983–1984 [9] and [10]. Genotype G9 strains re-emerged in early to

mid 1990s and the global prevalence has increased, such that G9 in combination with P[8], P[4] and P[6] have been detected in over 55 countries in Europe, Asia, Africa, South and North America and represent the dominant genotype in some regions during the past decade [5] and [8]. The development those and implementation of efficacious vaccination programs against rotavirus are a global priority. Two live-oral vaccines are currently available on the global market; Rotarix™ and RotaTeq™, and are licensed in over 100 and 85 countries worldwide respectively. They are included in the routine vaccination programs of many countries including the USA, Brazil, Panama, Venezuela, Belgium and Australia [11]. Rotarix™ is a live-attenuated monovalent vaccine, possessing a genotype G1P[8] strain, while RotaTeq™ is a live-attenuated pentavalent vaccine that contains five genetically distinct human-bovine reassortant virus strains [12] and [13]. Each reassortant strain contains a human gene encoding one of the outer capsid proteins within a bovine WC3 strain backbone (G6P[5]). Four of the reassortant strains have a VP7 gene encoding G1, G2, G3 or G4 and one reassortant strain carries the VP4 gene encoding P[8] [13].

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