Summary auto-generated
This study evaluated a recombinant human adenovirus type 5 (Ad5) vector expressing the simian immunodeficiency virus (SIV) p55 Gag antigen as a potential vaccine candidate. The researchers administered the virus (Ad404p55) to C57Bl/6 mice via intraperitoneal, oral, or intranasal routes and measured immune responses over time. Intraperitoneal immunization induced both plasma antibodies to SIV p27 (a capsid component of Gag) and cytotoxic T lymphocytes (CTLs) against p27. Oral immunization produced variable results: in responding animals, IgG antibodies persisted for over one year and p27-specific CTLs were detectable for at least six months. Intranasal immunization generated delayed CTL responses but minimal detectable plasma antibodies to SIV antigens. Interestingly, some orally and intranasally immunized animals showed p27-specific CTL responses without detectable plasma IgG antibodies. The study did not detect mucosal IgA responses in gut or respiratory tract despite repeated attempts. These findings suggest that oral and intranasal administration of Ad recombinants could be practical routes for inducing long-term cellular immunity to vaccine antigens, though optimization strategies may be needed to improve infection rates and consistency of responses.
Key findings
- Recombinant adenovirus expressing SIV Gag antigen elicited long-lived immune responses in mice, with plasma IgG antibodies persisting over one year and CTL responses detectable for at least six months following oral immunization.
- Oral and intranasal immunization routes produced different immune response patterns compared to intraperitoneal administration, with some animals generating p27-specific CTL responses without detectable serum IgG antibodies.
- Route of administration significantly influenced response characteristics: intraperitoneal immunization reliably induced both humoral and cellular immunity, while oral and intranasal routes produced more variable results but avoided parenteral injection.
- Not all orally immunized animals became infected by the vaccine virus, suggesting that encapsulation or adjuvants may be needed to improve the reliability of mucosal vaccination with adenovirus vectors.
- Despite mucosal immunization routes, no local IgA responses were detected in fecal, intestinal, or lung samples, indicating that mucosal immune stimulation did not occur as expected.
This summary was generated automatically from the article PDF and is not part of the original publication. Refer to the PDF for the authoritative text.
Abstract
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.