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Title: Evaluation of efficacy, potential for vector transmission and duration of immunity testing of MP-12, an attenuated Rift Valley fever virus vaccine candidate, in sheep

Author
item MILLER, MYRNA - University Of Wyoming
item BENNETT, KRISTINE - National Centre For Disease Control
item Drolet, Barbara
item LINDSAY, ROBBIN - Public Health Agency Of Canada
item MECHAM, JAMES - Retired ARS Employee
item REEVES, WILL - United States Air Force
item WEINGARTL, HANNA - Canadian Food Inspection Agency
item Wilson, William

Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/30/2015
Publication Date: 8/1/2015
Publication URL: http://handle.nal.usda.gov/10113/62677
Citation: Miller, M.M., Bennett, K., Drolet, B.S., Lindsay, R., Mecham, J.O., Reeves, W.K., Weingartl, H.M., Wilson, W.C. 2015. Evaluation of efficacy, potential for vector transmission and duration of immunity testing of MP-12, an attenuated Rift Valley fever virus vaccine candidate, in sheep. Clinical and Vaccine Immunology. 22(8):930-937. doi:10.1128/CVI.00114-15.

Interpretive Summary: The study describes the evaluation of a recently conditionally licensed vaccine for for the mosquito-borne virus Rift Valley fever, which causes severe to lethal disease in domestic ruminants and man. The disease is endemic is Sub-Saharan Africa and could be accidentally introduced into non-endemic countries. This study demonstrated presence of an immune response for up to two years and safety of the vaccine due to inability of mosquitoes to be infected upon feeding on vaccinated lambs.

Technical Abstract: Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. There are currently no fully licensed vaccines for this arthropod-borne virus in the US. Studies in sheep and cattle have found an attenuated strain of RVFV, MP-12, to be both safe and efficacious, and a conditional license of this vaccine (Zoetis, Inc. Florham Park, NJ) for use in livestock has been issued pending further testing. The purpose of this study is to determine the vaccine’s potential for vector transmission, ability to prevent disease and viremia from virulent challenge, and duration of immunity to 24 months post-vaccination. Vaccination experiments were conducted in sheep, including vector transmission using 4 mosquito species common to North America, measuring neutralizing antibodies to 24 months post vaccination, and challenge with virulent virus. We demonstrate that a single dose elicits neutralizing antibodies with titers >1:40 at 24 months post vaccination, and antibodies measured by competitive enzyme linked immunosorbent assay targeting three viral proteins: N, N-terminal half of glycoprotein GN (GNn), and NSs, gave similar results. Vaccinated sheep were protected from clinical signs after challenge with wild-type virus and had only viral RNA detected at one-day post infection in some sheep, while control sheep had fever and high-titered viremia extending for five days. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates sterilizing immunity to virulent challenge with antibody duration of at least 2 years without evidence of risk for vector transmission.