Intranasal Vaccination with the Recombinant Listeria monocytogenes ΔactA prfA* Mutant Elicits Robust Systemic and Pulmonary Cellular Responses and Secretory Mucosal IgA

We previously showed that recombinant (r) Listeria monocytogenes carrying Delta actA and a selected prfA* mutation (r-Listeria Delta actA prfA*) secreted > 100-fold more immunogen in broth culture than wild-type r-Listeria or r-Listeria Delta actA and elicited much greater cellular and humoral immune responses than r-Listeria Delta actA after intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-Listeria Delta actA prfA* vaccine candidates. Intranasal vaccination of mice with r-Listeria Delta actA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-gamma(+)) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-gamma(+) cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-Listeria Delta actA prfA* delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-Listeria Delta actA prfA* appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.