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

Myrna M. Miller, Kristine E. Bennett, Barbara S. Drolet, Robbin Lindsay, James O. Mecham, Will K. Reeves, Hana M. Weingarti, William C. Wilson
Clinical and Vaccine Immunology 2015 v.22 no.8 pp. 930-937
sterilizing immunity, viremia, Rift Valley fever phlebovirus, vaccination, strains, risk, enzyme-linked immunosorbent assay, viruses, virulence, glycoproteins, humans, Culicidae, cattle, neutralizing antibodies, virus transmission, sheep, vaccines, viral proteins, RNA, fever, United States, Africa
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.