@article{mbs:/content/journal/jgv/10.1099/vir.0.82126-0, author = "Reimerink, Johan H. J. and Boshuizen, Jos A. and Einerhand, Alexandra W. C. and Duizer, Erwin and van Amerongen, Geert and Schmidt, Nico and Koopmans, Marion P. G.", title = "Systemic immune response after rotavirus inoculation of neonatal mice depends on source and level of purification of the virus: implications for the use of heterologous vaccine candidates", journal= "Journal of General Virology", year = "2007", volume = "88", number = "2", pages = "604-612", doi = "https://doi.org/10.1099/vir.0.82126-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.82126-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "Rotavirus is an important cause of morbidity and mortality worldwide and vaccines are currently under development, with clinical trails conducted in humans worldwide. The immune responses in infant BALB/c mice were examined following oral inoculation with murine rotavirus EDIM (2×104 focus-forming units) and with three CsCl gradient-purified fractions of heterologous simian rotavirus SA11 (standardized at 2×106 CCID50) that differed in antigen composition: fraction 1 was enriched for double-layered rotavirus particles, fraction 2 for triple-layered particles and fraction 3 consisted mainly of cell components. Diarrhoea and high IgG responses, but marginal IgA responses, were observed after inoculation with all three SA11 fractions. Virus shedding was observed in all EDIM-inoculated mice, but in none of the SA11-inoculated mice. Rotavirus-specific IgG1 : 2a ratios were similar in mice inoculated with EDIM and SA11 fraction 1, but higher for SA11 fraction 3- and lower for SA11 fraction 2-inoculated mice. A higher IgG1 : 2a ratio indicates a more Th2-like immune response. This undesirable response is apparently mostly induced by inoculation with heterologous rotavirus in the presence of abundant cell-associated and soluble rotavirus proteins, compared with infection with a more purified preparation or with homologous virus. These data show that, following inoculation with a standardized amount of infectious virus, the composition of the fraction influences the outcome of the immune responses significantly.", }