BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6,020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time RT-PCR followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HR) of infection among children with versus without prior exposure. RESULTS: Norovirus was detected in 1,288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR=0.35; p=0.015), GI.7 (HR=0.19; p=0.022), GII.4 (HR=0.39; p<0.001), and GII.6 (HR=0.52; p=0.006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR=0.52; p=0.005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to re-infection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.
BACKGROUND: Norovirus is a leading cause of acute gastroenteritis worldwide yet there is limited information on homotypic or heterotypic protection following natural infection to guide vaccine development. METHODS: A total of 6,020 stools collected from 299 Peruvian children between 2010 and 2014 were tested by norovirus real-time RT-PCR followed by sequence-based genotyping. Cox proportional hazards models were used to derive adjusted hazard ratios (HR) of infection among children with versus without prior exposure. RESULTS: Norovirus was detected in 1,288 (21.3%) samples. GII.4 (26%), GII.6 (19%), and GI.3 (9%) viruses accounted for 54% of infections. Homotypic protection for GI.3 (HR=0.35; p=0.015), GI.7 (HR=0.19; p=0.022), GII.4 (HR=0.39; p<0.001), and GII.6 (HR=0.52; p=0.006) infections was observed. Hazard analysis showed that children with prior GII.4 infection exhibited heterotypic protection with a 48% reduction of subsequent GI.3 infection (HR=0.52; p=0.005). Prior exposure to GI.3, GII.2, and GII.17 infections enhanced susceptibility to subsequent infections with several other norovirus genotypes. CONCLUSIONS: Children up to 2 years of age infected with GII.4 noroviruses demonstrated both homotypic and heterotypic protection to re-infection with other genotypes. These data support the need for ongoing vaccine development efforts with GII.4 as the main component and caution the inclusion of genotypes that may enhance susceptibility to infections.
Authors: A Kroneman; H Vennema; K Deforche; H v d Avoort; S Peñaranda; M S Oberste; J Vinjé; M Koopmans Journal: J Clin Virol Date: 2011-04-21 Impact factor: 3.168