Distinct Pathological Changes in Preweaning Mice Infected with Live-Attenuated Rift Valley Fever Virus Strains.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101509722 Publication Model: Electronic Cited Medium: Internet ISSN: 1999-4915 (Electronic) Linking ISSN: 19994915 NLM ISO Abbreviation: Viruses Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Rift Valley fever virus*/pathogenicity ; Rift Valley fever virus*/immunology ; Rift Valley fever virus*/genetics ; Rift Valley Fever*/virology ; Rift Valley Fever*/pathology ; Rift Valley Fever*/prevention & control ; Rift Valley Fever*/immunology ; Vaccines, Attenuated*/immunology ; Vaccines, Attenuated*/administration & dosage ; Viral Vaccines*/immunology ; Viral Vaccines*/administration & dosage ; Mice, Inbred C57BL* ; Disease Models, Animal*; Animals ; Mice ; Virulence ; Female

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Middle East. Live-attenuated RVF vaccines have been studied for both veterinary and human use due to their strong immunogenicity and cost-effective manufacturing. The live-attenuated MP-12 vaccine has been conditionally approved for veterinary use in the U.S.A., and next-generation live-attenuated RVF vaccine candidates are being actively researched. Assessing the virulence phenotype of vaccine seeds or lots is crucial for managing vaccine safety. Previously, preweaning 19-day-old outbred CD1 mice have been used to evaluate the MP-12 strain. This study aimed to characterize the relative virulence of three live-attenuated RVF vaccine strains in 19-day-old inbred C57BL/6 mice: the recombinant MP-12 (rMP-12), the RVax-1, and the ∆NSs-∆NSm-rZH501 strains. Although this mouse model did not show dose-dependent pathogenesis, mice that succumbed to the infection exhibited distinct brain pathology. Mice infected with ∆NSs-∆NSm-rZH501 showed an infiltration of inflammatory cells associated with infected neurons, and focal lesions formed around virus-infected cells. In contrast, mice infected with rMP-12 or RVax-1 showed a minimal association of inflammatory cells in the brain, yet the virus spread diffusely. The preweaning model is likely useful for evaluating host responses to attenuated RVFV strains, although further refinement may be necessary to quantitate the virulence among different RVFV strains or vaccine lots.

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T32AI007526-22 NIAID Emerging and Tropical Infectious Diseases Training Program Grant, Pre-Doctoral Fellowship; R01AI150917 NIH/NIAID

Keywords: MP-12; RVax-1; Rift Valley fever; age dependent; encephalitis; hepatitis; live-attenuated vaccine; mouse; preweaning; ∆NSs-∆NSm-rZH501

0 (Vaccines, Attenuated)
0 (Viral Vaccines)

Date Created: 20240727 Date Completed: 20240728 Latest Revision: 20240729

20240729

PMC11281583

10.3390/v16070999

39066162