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

J Gen Virol. 2007 Feb;88(Pt 2):604-612. doi: 10.1099/vir.0.82126-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn*
  • Antibodies, Viral / blood
  • Antigens, Viral* / administration & dosage
  • Antigens, Viral* / immunology
  • Antigens, Viral* / isolation & purification
  • Centrifugation, Isopycnic
  • Cesium
  • Chlorides
  • Female
  • Intestine, Small / pathology
  • Intestine, Small / virology
  • Mice
  • Mice, Inbred BALB C
  • Pregnancy
  • Rotavirus Infections / immunology
  • Rotavirus Infections / pathology
  • Rotavirus Infections / prevention & control*
  • Rotavirus Vaccines / immunology*
  • Rotavirus* / immunology
  • Rotavirus* / isolation & purification
  • Rotavirus* / pathogenicity
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Viral Proteins* / administration & dosage
  • Viral Proteins* / immunology
  • Viral Proteins* / isolation & purification

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Chlorides
  • Rotavirus Vaccines
  • Viral Proteins
  • Cesium
  • cesium chloride