VP1 pseudocapsids, but not a glutathione-S-transferase VP1 fusion protein, prevent polyomavirus infection in a T-cell immune deficient experimental mouse model

J Med Virol. 2003 Jun;70(2):293-300. doi: 10.1002/jmv.10394.

Abstract

The ability to vaccinate against polyomavirus infection in a T-cell deficient as well as a normal immune context was studied using polyomavirus major capsid protein (VP1) pseudocapsids (VP1-ps) or a glutathione-S-transferase-VP1 (GST-VP1) fusion protein. VP1-ps (1 or 10 microg) were administered subcutaneously, alone or together with Freund's complete and incomplete adjuvant, to CD4(-/-)8(-/-) T-cell deficient or normal C57Bl/6 mice on four occasions. Alternatively, CD4(-/-)8(-/-) and normal mice were inoculated with either GST-VP1 or Py-VP1-ps (5 microg). Following immunisation, antibody titres were tested by ELISA to VP1-ps or GST-VP1 or by haemagglutination inhibition (HAI). Mice were then infected with polyomavirus. Three weeks post-infection, the mice were killed and examined for the presence of polyomavirus DNA by PCR. Viral DNA was not detected in CD4(-/-)8(-/-) mice immunised with either VP1-ps alone or in combination with Freund's complete and incomplete adjuvant, or in any of the normal mice immunised with VP1-ps or GST-VP1. However, viral DNA was detected in 2/5 of the CD4(-/-)8(-/-) mice immunised with GST-VP1 and in non-immunised controls. Greater antibody titres were observed to VP1-ps than to GST-VP1 in CD4(-/-)8(-/-) mice after VP1-ps compared to GST-VP1 immunisation and antibody responses were better in normal than in immune-deficient mice. Only immunisation with VP1-ps resulted in haemagglutination inhibition. Complete protection against polyomavirus infection in the T-cell deficient context was obtained with VP1-ps, but not with GST-VP1, immunisation using the present vaccination protocol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / blood
  • Capsid
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Capsid Proteins / metabolism
  • Disease Models, Animal
  • Glutathione Transferase / genetics
  • Glutathione Transferase / immunology
  • Glutathione Transferase / metabolism
  • Guinea Pigs
  • Hemagglutination
  • Humans
  • Immunization
  • Immunologic Deficiency Syndromes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Polyomavirus / immunology
  • Polyomavirus Infections / prevention & control*
  • Polyomavirus Infections / virology
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology*
  • Tumor Virus Infections / prevention & control*
  • Tumor Virus Infections / virology
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Recombinant Fusion Proteins
  • VP1 protein, polyomavirus
  • Viral Vaccines
  • Glutathione Transferase