In vivo molecular imaging analysis of a Nasal vaccine that induces protective immunity against botulism in nonhuman primates

Nasal administrationis an effective route foraneedle-free vaccine. However, nasally administered Ags have the potential toreach the CNS directly from the nasal cavity, thus raising safety concerns.Inthis study, weperformed real-time quantitative trackingofanasal vaccine candidate for botulism, which is a nontoxic subunit fragment of Clostridium botulinum type A neurotoxin (BoHc/A) effective in the induction of the toxin-neutralizing immune response, by using¹⁸F-labeled BoHc/A-positron-emission tomography, an in vivo molecular imaging method. This method provides results that are consistent with direct counting of [¹⁸F] radioactivity or the traditional [ ¹¹¹In]-radiolabel method in dissected tissues of mice and nonhuman primates. We found no deposition of BoHc/A in the cerebrum or olfactory bulb after nasal administration of¹⁸F-labeled BoHc/A in both animals. We also established a real-time quantitative profile of elimination of this nasal vaccine candidate and demonstrated that it induces highly protective immunity against botulism in nonhuman primates. Our findings demonstrate the efficiency and safety of a nasal vaccine candidate against botulism in mice and nonhuman primates using in vivo molecular imaging.