Live-Attenuated Rift Valley Fever Virus Encoding Peste des Petits Ruminants Virus H or F Antigens Provides Immunity upon a Single Dose in Sheep

Introduction/Background: Rift Valley fever virus (RVFV) and peste des petits ruminants virus (PPRV) are significant pathogens affecting small ruminants, causing substantial economic losses in the affected regions. The development of effective vaccines against both viruses is crucial for disease control. Recombinant viruses expressing heterologous antigens have shown promise as multivalent vaccine candidates. Methods: Recombinant RVFVs were generated to express either the Hemagglutinin (H) or Fusion (F) proteins from the PPRV strain Nigeria 75/1. The stability of these recombinant viruses was assessed through consecutive passages in cell culture. Immunogenicity studies were conducted in both mice and sheep to evaluate the induction cellular and humoral immune responses capable of protecting against both RVFV and PPRV. Results: The recombinant RVFVs expressing PPRV H or F proteins demonstrated stability in cell culture, maintaining high viral titers and consistent transgene expression over five passages. Immunization of mice resulted in the production of serum antibodies capable of neutralizing both RVFV and PPRV in vitro. In sheep, the recombinant viruses elicited both neutralizing antibodies and cell-mediated immune responses specific to PPRV and RVFV antigens. Conclusions: The successful generation and characterization of recombinant RVFVs expressing PPRV antigens demonstrate the potential of using rationally attenuated RVFV as a vector for multivalent vaccine development. These results suggest that this approach could be a viable strategy for simultaneous immunization against Rift Valley fever and other prevalent ruminant diseases, such as peste des petits ruminants.