Abstract
The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here, we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1826 adjuvants, administered by the parenteral and nasal routes. Using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen; however, only parenterally primed cells responded to booster immunization. Subcutaneous (SC) priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that SC priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.
Highlights
Heterologous combinations of vaccine formulations for priming and boosting the immune system represent a strategic tool for the development of generation vaccines
Frequencies of Tet+ T cells detected in naïve mice or elicited by priming or primeboost combination are reported. Priming with both CAF01 by the SC route and CpG by the intra nasal (IN) route induced a significant increase of Tet+ T cell frequency compared to naïve animals, while CAF01 administered by the IN route was not effective in stimulating antigen-specific T-cell priming
Our data show that parenteral priming with H56 antigen and CAF01 adjuvant followed by nasal boosting with vaccine antigen and CpG is the prime-boost combination able to elicit the strongest peptide-specific CD4+ T cell response in both spleen and lungs, compared to the other homologous or heterologous prime-boost combinations tested
Summary
Heterologous combinations of vaccine formulations for priming and boosting the immune system represent a strategic tool for the development of generation vaccines. CD4+ T cell responses upon prime-boost combinations vaccination strategies, different routes of delivery, such as mucosal and parenteral, can be combined in order to induce immune responses in both the local and systemic compartments [7, 8]. CD4+ T-cell priming properties of different adjuvants [10,11,12], delivery systems [13, 14], and immunization routes [15,16,17], have been characterized for a rational design of effective prime-boost combinations [8]. The route of immunization deeply influences the local and systemic immune response [18,19,20] and affects the polarization of CD4+ T effector cells into different helper subtypes. The use of combined prime-boost immunization can impact on the efficiency and the localization of the immune response to a vaccine formulation
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