A recombinant human adenovirus expressing the simian immunodeficiency virus Gag antigen can induce long-lived immune responses in mice.
Human adenovirus type 5 can be used as a vector to elicit immune responses to antigens expressed from heterologous DNA sequences incorporated into the viral genome, for example in mice immunized intraperitoneally. We have used a recombinant adenovirus which expresses the p55gag antigen of simian immunodeficiency virus to evaluate the nature and longevity of the response elicited when administered to mice by alterative routes which translate more readily to larger animals and man. In C57BI/6 mice immunized orally with a single dose of virus, a majority of the animals which showed evidence of responding to the immunogen by producing an anti-adenovirus response also produced a plasma antibody response to Gag which persisted for more than 1 year and a Gag-specific cytotoxic T cell response that could be detected for at least 6 months. In a minority of similarly immunized responding animals, only a cytotoxic response to Gag was observed although both humoral and cellular responses to adenovirus antigens were seen; intranasal immunization produced a Gag-specific response similar to this latter pattern. These findings suggest that delivery of adenovirus recombinants orally or intranasally may be a useful strategy for eliciting long-term cytotoxic T cell memory responses in splenocytes to candidate vaccine antigens.
Flanagan
B
B
Department of Biological Sciences, University of Warwick, Coventry, UK.
Pringle
C R
CR
Leppard
K N
KN
D000260:Adenoviruses, Human / Q000235:genetics*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000914:Antibodies, Viral; D000956:Antigens, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins