VP1 pseudocapsids, but not a glutathione-S-transferase VP1 fusion protein, prevent polyomavirus infection in a T-cell immune deficient experimental mouse model.
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.
Vlastos
Andrea
A
Department of Oncology-Pathology, Karolinska Institute, Karolinska Hospital, SE-171 76 Stockholm, Sweden. Andrea.Vlastos@cck.ki.se
Andreasson
Kalle
K
Tegerstedt
Karin
K
Holländerová
Dana
D
Heidari
Shirin
S
Forstová
Jitka
J
Ramqvist
Torbjörn
T
Dalianis
Tina
T
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D006384:Hemagglutination; D006801:Humans; D007114:Immunization; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011120:Polyomavirus / Q000276:immunology; D027601:Polyomavirus Infections / Q000517:prevention & control* / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control* / Q000821:virology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000914:Antibodies, Viral; D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; D014765:Viral Vaccines; D005982:Glutathione Transferase