Vaccine-derived NSP2 segment in rotaviruses from vaccinated children with gastroenteritis in Nicaragua

Department of Microbiology, University of León, UNAN-León, Nicaragua.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases (Impact Factor: 3.02). 04/2012; 12(6):1282-94. DOI: 10.1016/j.meegid.2012.03.007
Source: PubMed


Rotavirus (RV) vaccination programs have been established in several countries using the human-attenuated G1P[8] monovalent vaccine Rotarix (GlaxoSmithKline) and/or the human-bovine reassortant G1, G2, G3, G4, P[8] pentavalent vaccine RotaTeq (Merck). The efficacy of both vaccines is high (∼90%) in developed countries, but can be remarkably lower in developing countries. For example, a vaccine efficacy against severe diarrhea of only 58% was observed in a 2007-2009 Nicaraguan study using RotaTeq. To gain insight into the significant level of vaccine failure in this country, we sequenced the genomes of RVs recovered from vaccinated Nicaraguan children with gastroenteritis. The results revealed that all had genotype specificities typical for human RVs (11 G1P[8], 1 G3P[8]) and that the sequences and antigenic epitopes of the outer capsid proteins (VP4 and VP7) of these viruses were similar to those reported for RVs isolated elsewhere in the world. As expected, nine of the G1P[8] viruses and the single G3P[8] virus had genome constellations typical of human G1P[8] and G3P[8] RVs: G1/3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. However, two of the G1P[8] viruses had atypical constellations, G1-P[8]-I1-R1-C1-M1-A1-N2-T1-E1-H1, due to the presence of a genotype-2 NSP2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the bovine N2 NSP2 gene of RotaTeq, indicating that the two atypical viruses originated via reassortment of human G1P[8] RVs with RotaTeq viruses. Together, our data suggest that the high level of vaccine failure in Nicaraguan is probably not due to antigenic drift of commonly circulating virus strains nor the emergence of new antigenetically distinct virus strains. Furthermore, our data suggest that the widespread use of the RotaTeq vaccine has led to the introduction of vaccine genes into circulating human RVs.

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    • "M2 100 100 100 99 100 96 77 99 89 83 99 100 100 99 99 100 100 99 94 100 99 97 98 74 100 99 100 98 99 100 85 99 86 77 87 100 70 0 . 2 E Fig . 1 . ( Continued ) J . Med . Virol . DOI 10 . 1002 / jmv isolated globally [ Wyatt et al . , 1983 ; Rahman et al . , 2007 ; Matthijnssens et al . , 2008a ; Jere et al . , 2011 ; Bucardo et al . , 2012 ]"
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    ABSTRACT: Group A rotaviruses (RVAs) are the leading cause of severe gastroenteritis and eventually death among infants and young children worldwide, and disease prevention and management through vaccination is a public health priority. In August 2009, Rotarix™ was introduced in the South African Expanded Programme on Immunisation. As a result, substantial reductions in RVA disease burden have been reported among children younger than 5 years old. Rotavirus strain surveillance post-vaccination is crucial to, inter alia, monitor and study the evolution of vaccine escape strains. Here, full-genome sequence data for the 11 gene segments from 11 South African G1P[8] rotavirus strains were generated, including 5 strains collected from non-vaccinated children during the 2004-2009 rotavirus seasons and 6 strains collected from vaccinated children during the 2010 rotavirus season. These data were analyzed to gain insights into the overall genetic makeup and evolution of South African G1P[8] rotavirus strains and to compare their genetic backbones with those of common human Wa-like RVAs from other countries, as well as with the Rotarix™ and RotaTeq™ G1P[8] vaccine components. All 11 South African G1P[8] strains revealed a complete Wa-like genotype constellation of G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1. On the basis of sequence similarities, the South African G1P[8] strains (with the exception of strain RVA/Human-wt/ZAF/1262/2004/G1P[8]) were closely related to each other (96-100% identity in all gene segments). Comparison to the Rotarix™ and RotaTeq™ G1P[8] vaccine components revealed a moderate nucleotide identity of 89-96% and 93-95%, respectively. The results indicated that none of the gene segments of these 11 South African G1P[8] strains were vaccine-derived. This study illustrates that large-scale next generation sequencing will provide crucial information on the influence of the vaccination program on evolution of rotavirus strains. This is the first report to describe full genomic analyses of G1P[8] RVA strains collected from both non-vaccinated and vaccinated children in South Africa. J. Med. Virol. 9999: XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 01/2015; 87(1). DOI:10.1002/jmv.23971 · 2.35 Impact Factor
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    • "/G4P[14] and Gottfried has been reported previously from human RVA cases from Bulgaria, Hungary, India, and Nicaragua and is thought to be of porcine origin (Bucardo et al., 2012; Mladenova et al., 2012; Mukherjee et al., 2011; Papp et al., 2013). For all genes except VP4, NSP3, and NSP4, the Barbados strain genes cluster within supported clades containing both human and porcine RVA strains and, in the cases of VP1, VP2, VP3, and NSP1, a small number of equine and bovine strains as well (Figs. "
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    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 09/2014; 28. DOI:10.1016/j.meegid.2014.09.020 · 3.02 Impact Factor
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    • "In general, the gene segments of KisB332 showed lower nucleotide sequence identities to known contemporary and historic human or animal RVAs, especially in the VP6, VP1, VP2 and NSP1 genes (figures 6 and [7]). Although these gene segments of KisB332 were only relatively distantly related to known RVA strains, they showed the highest relatedness to RVA/Human-wt/NCA/24J/2010/G1P[8] (for VP6), RVA/Pig-tc/USA/OSU/1977/G5P9[7] (VP1), RVA/Pig-wt/KOR/K71/2006/G5P7 (VP2) and human reference strain RVA/Human-tc/USA/WI61/1983/G9P1A[8] (NSP1) [56], [57]. The VP3 of KisB332 was most closely related to porcine RVA strain OSU (figure 7). "
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