Protective local cytotoxic T lymphocyte responses stimulated by mucosal vaccination

To design effective mucosal vaccines against pathogens such as HIV the relative importance of different immune mechanisms in mediating protection needs to be determined and strategies to optimize their induction should be developed.In a model system, Belyakov et al.1xThe importance of local mucosal HIV-specific CD8+ cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. Belyakov, I.M. et al. J. Clin. Invest. 1998; 102: 2072–2081Crossref | PubMedSee all References1 have dissected the mechanisms by which mucosal immunization with an HIV peptide protects mice against subsequent intrarectal challenge with recombinant vaccinia virus expressing HIV-1 gp160. The peptide immunogen stimulates both antibody and cytotoxic T lymphocyte (CTL) responses. However, the construction of the challenge virus was such that gp160 was expressed in infected host cells but was not incorporated into the virus particle itself, making a protective role for neutralizing antibody unlikely. Instead, long-lasting resistance to mucosal infection was mediated by CD8+ CTLs. Protective mucosal immunization induced CTLs in both local tissues and the spleen; subcutaneous immunization only induced CTLs in the spleen and was not protective, suggesting that local responses are necessary for protection.Recombinant interleukin 12 (rIL-12), mixed with the cationic lipofection agent DOTAP and administered with the peptide vaccine, increased CTL responses and protection. When given systemically, IL-12 did not enhance CTL generation. Locally applied low doses of cytokine might be an effective way of manipulating immune responses in other contexts; it might also avoid problems, such as toxicity, that are associated with systemic administration.