Evaluation of Intranasal Immunization Procedure for RSV Vaccines in Non-Human Primates using PET

1133 Objectives Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in children and seniors worldwide. Despite the prevalence of the disease, there is currently no RSV vaccine, and therapeutic options are limited. Common practices for intranasal (IN) delivery in rodents provide a range of outcomes that could result in ambiguous interpretation. We have since refined methods to retain vaccine inoculum solely in the upper respiratory tract (URT) while providing sufficient immune responses to protect against viral challenge. Non-human primates are equally invaluable to assess novel RSV vaccines preclinically, with African green monkeys (C. aethiops) commonly used for evaluating efficacy and safety of RSV vaccines. We evaluated whether traditional intranasal immunization methodologies utilized in non-human primate studies result in vaccine deposition in both the upper and lower respiratory tract, providing a pathway to an immune response that would not be available in a clinical setting. Methods African Green monkey (N=6) were dosed intranasally with either 250 µL or 100 µL RSV vaccine radiolabeled with 64Cu. Monkeys were fasted and anesthetized with Ketamine/Xylazine followed by Propofol. A 30 minute PET scan of the URT was started followed immediately by IN delivery of vaccine. A 5 minute per bed whole body scan was acquired 1 hour post-dose to determine distribution to the lower respiratory tract. Blood samples were taken prior to scanning and 28 days post-dose to determine immunogenicity. PET images were analyzed to determine the percent of injected radiotracer in nasal cavity, pharynx/larynx, trachea, and lungs. Results PET analysis results are in Table 1. This analysis revealed substantial lung accumulation (up to 34%) in animals receiving the 250 µL dose, while animals receiving the 100 µL dose had very low lung accumulation (2% or less). Serum titers of the vaccine determined animals were positive at the highest dilution factor at 28 days post-dose for both 100 µL and 250 µL doses. Conclusions PET results demonstrated that nasal administration of 250 µL of 64Cu-RSV leads to variable, but substantial lung accumulation. Reduction of dose to 100 µL resulted in substantial reduction of pulmonary immunization accumulation with no loss of immunogenicity.