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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