Evaluation of the Safety and Efficacy of the Respiratory Syncytial Virus FG Chimeric Vaccine KD-409 in Rodent Models for Maternal and Pediatric Vaccination

Abstract

Respiratory syncytial virus (RSV) causes severe infection in neonates and infants. However, a suitable RSV vaccine for children has yet to be approved. We developed an effective and safe RSV vaccine for newborns and children. Accordingly, we evaluated the safety and efficacy of the RSV FG chimeric protein KD-409, which incorporates a highly conserved region of the RSV G protein into the RSV F protein, in several rodent models. We confirmed the effect of our vaccine-induced antibody transfer using a guinea pig model. Subsequently, we evaluated the exacerbation of infection in a BALB/c mouse model of passive immunity, which was designed to mimic the vaccination of pregnant women. Notably, KD-409 in the presence of alum did not exacerbate infection, which occurred upon administering pre-F with alum. Our active immunization model of BALB/c mice, which simulated vaccination with a pediatric vaccine, suggested that KD-409 with alum was less likely to exacerbate inflammation than FI-RSV or pre-F with alum. The efficacy was evaluated in a cotton rat model, in which KD-409 demonstrated better protection against infection than pre-F without adjuvant, the only currently approved formulation for immunizing pregnant women. Collectively, antibody transfer in pregnant guinea pigs during immunization, safety in mice during passive and active immunization, and efficacy in cotton rats demonstrate the high potential of KD-409 as a novel vaccine candidate. Our results provide insights into the potential of KD-409 as a safe and effective next-generation RSV vaccine that can cover the neonatal-to-pediatric age range. IMPORTANCEThe safety and efficacy of KD-409, an RSV FG chimeric protein, were evaluated in appropriate rodents. We found that KD-409 was less likely to exacerbate infections and symptoms, and exhibited superior safety and efficacy to pre-F without adjuvant, which is the only approved vaccine for pregnant women. Thus, KD-409 represents a valuable immunization modality for maternal and pediatric immunization.