TY - JOUR
T1 - MP-12 virus containing the clone 13 deletion in the NSs gene prevents lethal disease when administered after Rift Valley fever virus infection in hamsters
AU - Gowen, Brian B.
AU - Westover, Jonna B.
AU - Sefing, Eric J.
AU - Bailey, Kevin W.
AU - Nishiyama, Shoko
AU - Wandersee, Luci
AU - Scharton, Dionna
AU - Jung, Kie Hoon
AU - Ikegami, Tetsuro
N1 - Publisher Copyright:
© 2015 Gowen, Westover, Sefing, Bailey, Nishiyama, Wandersee, Scharton, Jung and Ikegami.
PY - 2015
Y1 - 2015
N2 - Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.
AB - Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) causes a range of illnesses that include retinitis, fulminant hepatitis, neurologic disease, and hemorrhagic fever. In hospitalized individuals, case fatality rates can be as high as 10-20%. There are no vaccines or antivirals approved for human use to prevent or treat severe RVFV infections. We previously tested the efficacy of the MP-12 vaccine strain and related variants with NSs truncations as a post-exposure prophylaxis in mice infected with wild-type pathogenic RVFV strain ZH501. Post-exposure efficacy of the rMP12-C13type, a recombinant MP-12 vaccine virus which encodes an in-frame truncation removing 69% of the NSs protein, resulted in 30% survival when administering the virus within 30 min of subcutaneous ZH501 challenge in mice, while the parental MP-12 virus conferred no protection by post-exposure vaccination. Here, we demonstrate uniform protection of hamsters by post-exposure vaccination with rMP12-C13type administered 6 h post-ZH501 infection while no efficacy was observed with the parental MP-12 virus. Notably, both the MP-12 and rMP12-C13type viruses were highly effective (100% protection) when administered 21 days prior to challenge. In a subsequent study delaying vaccination until 8, 12, and 24 h post-RVFV exposure, we observed 80, 70, and 30% survival, respectively. Our findings indicate that the rapid protective innate immune response elicited by rMP12-C13type may be due to the truncated NSs protein, suggesting that the resulting functional inactivation of NSs plays an important role in the observed post-exposure efficacy. Taken together, the data demonstrate that post-exposure vaccination with rMP12-C13type is effective in limiting ZH501 replication and associated disease in standard pre-exposure vaccination and post-challenge treatment models of RVFV infection, and suggest an extended post-exposure prophylaxis window beyond that initially observed in mice.
KW - Phlebovirus
KW - Post-exposure
KW - Rift valley fever virus
KW - Vaccine
KW - Viral hemorrhagic fever
UR - http://www.scopus.com/inward/record.url?scp=84937131807&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937131807&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2015.00651
DO - 10.3389/fmicb.2015.00651
M3 - Article
C2 - 26175722
AN - SCOPUS:84937131807
SN - 1664-302X
VL - 6
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
IS - JUN
M1 - 651
ER -