Prime-Boost Strategies in Mucosal Immunization Affect Local IgA Production and the Type of Th Response

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.

Nanoformulation of synergistic TLR ligands to enhance vaccination against Entamoeba histolytica

“…Intranasal priming in particular has been shown to influence stronger Th1 polarization along with a higher local IgA response [42]. Similarly, mice receiving either an intranasal prime or boost were shown to also produce higher levels of IL-17A [42]. We saw a robust antigen specific gut IgA response, which can be a major advantage in the context of vaccines against enteric pathogens.…”

“…Mucosal immunization has been shown to elicit both local and systemic humoral as well as cellular responses in animal models and in humans [41]. Intranasal priming in particular has been shown to influence stronger Th1 polarization along with a higher local IgA response [42]. Similarly, mice receiving either an intranasal prime or boost were shown to also produce higher levels of IL-17A [42].…”

Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection

“…The priming and boosting strategy is demonstrated to be required to establish optimal T cell immunity. 21 However, current human inactivated influenza vaccines are given through intradermal or intramuscular injection, and thus fail to generate robust anti-influenza T cell immunity in the lung. It has been shown that the local boosting strategy can help establish robust memory T cells in peripheral tissues.…”

“…It has been shown that the local boosting strategy can help establish robust memory T cells in peripheral tissues. [21][22][23] In addition, robust resident T cell immunity in lung is critical to protect from acute influenza viral infection. [24][25][26] Nevertheless, little is known about the effects of pulmonary boosting vaccines with adjuvants on local development of antigen-specific Treg cells in lung.…”

Is Prime Boost Strategy a Promising Approach in HIV Vaccine Development?

“…The factors which favor development of mucosal immune responses include the mucosal or trans cutaneous immunization and the replicating nature of the vaccine agents [84,85]. A prime boost strategy with heterologous routes of administration based on the combination of mucosal and parenteral delivery has been attempted in a murine model for inducing immune responses at both mucosal and systemic levels [86]. Although mucosal route for vaccination is desired for its ease of administration and development of local immunity, mucosal vaccinations are faced with safety concerns and problems of lesser efficacy [87].…”