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

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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 μg) 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 μg). 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. J. Med. Virol. 70: 293–300, 2003.