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.
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 x 10(4) focus-forming units) and with three CsCl gradient-purified fractions of heterologous simian rotavirus SA11 (standardized at 2 x 10(6) CCID(50)) 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.
authors.affiliation: Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors.forename: Johan H J
authors.initials: JHJ
authors.lastname: Reimerink
authors.affiliation: Laboratory of Pediatrics, Pediatric Gastroenterology and Nutrition, Erasmus MC/Sophia, Rotterdam, The Netherlands.
authors.forename: Jos A
authors.initials: JA
authors.lastname: Boshuizen
authors.affiliation: Laboratory of Pediatrics, Pediatric Gastroenterology and Nutrition, Erasmus MC/Sophia, Rotterdam, The Netherlands.
authors.forename: Alexandra W C
authors.initials: AWC
authors.lastname: Einerhand
authors.affiliation: Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors.forename: Erwin
authors.initials: E
authors.lastname: Duizer
authors.affiliation: Central Animal Laboratory, National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Central Animal Laboratory, National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: Schmidt
authors.affiliation: Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors.forename: Marion P G
authors.initials: MPG
authors.lastname: Koopmans
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D002500:Centrifugation, Isopycnic; D002586:Cesium; D002712:Chlorides; D005260:Female; D007421:Intestine, Small / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D012401:Rotavirus / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity; D012400:Rotavirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D002712:Chlorides; D022243:Rotavirus Vaccines; D014764:Viral Proteins; D002586:Cesium; C028019:cesium chloride