Rift Valley fever virus (RVFV) is a mosquito-borne pathogen with
significant human and veterinary health consequences that periodically
emerges in epizootics. RVF causes fetal loss and death in ruminants and
in humans can lead to liver and renal disease, delayed-onset
encephalitis, retinitis, and in some cases severe hemorrhagic fever. A
live attenuated vaccine candidate (DDVax), was developed by the deletion
of the virulence factors NSs and NSm from a clinical isolate, ZH501, and
has proven safe and immunogenic in rodents, pregnant sheep and non-human
primates. Deletion of NSm also severely restricted mosquito midgut
infection and inhibited vector-borne transmission. To demonstrate
environmental safety, this study investigated the replication,
dissemination and transmission efficiency of DDVax in mosquitoes
following oral exposure compared to RVFV strains MP-12 and ZH501.
Infection and dissemination profiles were also measured in mosquitoes 7
days after feeding on goats inoculated with DDvax or MP-12. Hypothesis:
DDVax should infect mosquitoes at significantly lower rates than other
RVF strains and, due to lack of NSm, be transmission
incompetent. Exposure of Ae. aegypti and Cx. tarsalis to
6-8 log plaque forming units (PFU)/mL DDVax by
artificial bloodmeal resulted in significantly reduced DDVax infection
rates in mosquito bodies compared to controls. Plaque assays indicated
negligible transmission of infectious DDVax in Cx. tarsalis
saliva (1/140 sampled) and none in Ae aegypti saliva (0/120).
Serum from goats inoculated with DDVax or MP-12 did not harbor
detectable infectious virus by plaque assay at 1, 2, or 3
days-post-inoculation; infectious virus was, however, recovered from
mosquito bodies that fed on goats vaccinated with MP-12 (13.8% and
4.6%, respectively), but strikingly, DDvax positive mosquito bodies
were greatly reduced (4%, and 0%, respectively). Furthermore, DDVax
did not disseminate to legs/wings in any of the goat-fed mosquitoes.
Collectively, these results are consistent with a beneficial
environmental safety profile .
Safety study of Rift Valley Fever human vaccine candidate (DDVax) in mosquitoes
