Abstract
Combinations of different delivery routes for priming and boosting represent vaccination strategies that can modulate magnitude, quality, and localization of the immune response. A murine model was used to study T cell clonal expansion following intranasal (IN) or subcutaneous (SC) priming, and secondary immune responses after boosting by either homologous or heterologous routes. T cell primary activation was studied by using the adoptive transfer model of ovalbumin-specific transgenic CD4+ T cells. Both IN and SC immunization efficiently elicited, in the respective draining lymph nodes, primary clonal expansion of antigen-specific CD4+ T cells that disseminated toward distal lymph nodes (mesenteric and iliac) and the spleen. After boosting, a significant serum IgG response was induced in all groups independent of the combination of immunization routes used, while significant levels of local IgA were detected only in mice boosted by the IN route. Mucosal priming drove a stronger Th1 polarization than the systemic route, as shown by serum IgG subclass analysis. IFN-gamma production was observed in splenocytes of all groups, while prime-boost vaccine combinations that included the mucosal route, yielded higher levels of IL-17. Memory lymphocytes were identified in both spleen and draining lymph nodes in all immunized mice, with the highest number of IL-2 producing cells detected in mice primed and boosted by the nasal route. This work shows the critical role of immunization routes in modulating quality and localization of immune responses in prime-boost vaccine strategies.
Highlights
Most licensed vaccines include a priming dose and at least one boost of the same immunogen to generate an effective immune response in terms of increasing magnitude, quality, and localization
The presence of primed T cells at distal sites is due to migration of proliferated T cells from draining lymph nodes, as previously demonstrated (Ciabattini et al, 2011)
In the present work we show that prime-boost combinations by IN and SC routes affect the local and systemic immune responses in mice
Summary
Most licensed vaccines include a priming dose and at least one boost of the same immunogen to generate an effective immune response in terms of increasing magnitude, quality, and localization. Developed to combine recombinant DNA priming with viral vector boosting (McShane, 2002; Ranasinghe and Ramshaw, 2009), the heterologous prime-boost approach has been applied to many different combinations of delivery systems and has been tested in several clinical trials (Hill et al, 2010; Paris et al, 2010; Rowland and McShane, 2011; O’Hara et al, 2012; Sheehy et al, 2012). The heterologous prime-boost approach can be achieved by combining different routes of vaccination This strategy, principally based on the combination of mucosal and parenteral delivery, has the advantage of inducing immune responses in both the local and systemic compartments that are as strong or stronger than those resulting from homologous mucosal or parenteral vaccination alone (McCluskie et al, 2002; Glynn et al, 2005; Mapletoft et al, 2010; Pattani et al, 2012). The use of homologous or heterologous routes can impact on the efficiency and the localization of the immune response to a vaccine formulation
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