Abstract
While a new generation of vaccine vectors has been developed for eliciting cellular immune responses, little is known about the optimal routes for their administration or about the ramifications of the kinetics of in vivo vaccine antigen expression for immunogenicity. We evaluated the kinetics of vaccine antigen expression by real-time in vivo photon imaging and showed dramatic differences in these kinetics using different vectors and different routes of administration. Further, using a gamma interferon enzyme-linked immunospot assay to measure T-lymphocyte immune responses, we observed an association between the kinetics of vaccine antigen expression in vivo and the magnitude of vaccine-elicited memory T-lymphocyte responses. These results highlight the utility of the real-time in vivo photon-imaging technology in evaluating novel immunization strategies and suggest an association between the kinetics of vaccine antigen clearance and the magnitude of vaccine-elicited T-lymphocyte memory immune responses.
Highlights
While a new generation of vaccine vectors has been created to induce cellular immune responses, we know little about how to use them to maximize the generation of memory T-lymphocyte populations
While a new generation of vaccine vectors has been developed for eliciting cellular immune responses, little is known about the optimal routes for their administration or about the ramifications of the kinetics of in vivo vaccine antigen expression for immunogenicity
Luciferin is inoculated into mice that have received luciferaseexpressing immunogens, and the quantity of light emitted by this reaction is monitored in living mice [6]
Summary
While a new generation of vaccine vectors has been created to induce cellular immune responses, we know little about how to use them to maximize the generation of memory T-lymphocyte populations. The in vivo evaluation of new vaccine vectors to select optimal routes of administration, dose, and biodistribution has been difficult, requiring serial sacrifice of laboratory animals and assessment of individual organs for vaccine antigen expression. To simplify this process of vaccine evaluation, we have adopted an in vivo imaging system (IVIS) to measure the expression of luciferase by vaccine vectors. This imaging strategy harnesses the ability of the luciferase protein to catalyze the light-producing oxidation of the small molecule luciferin. Tion between the kinetics of antigen expression in vivo and the induction of long-term memory T cells
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