scholarly journals Safety study of Rift Valley Fever human vaccine candidate (DDVax) in mosquitoes

Author(s):  
Corey L. Campbell ◽  
Trey K. Snell ◽  
Susi Bennett ◽  
John H. Wyckoff ◽  
Darragh Heaslip ◽  
...  
Vaccine ◽  
2014 ◽  
Vol 32 (20) ◽  
pp. 2345-2349 ◽  
Author(s):  
Hana M. Weingartl ◽  
Charles K. Nfon ◽  
Shunzhen Zhang ◽  
Peter Marszal ◽  
William C. Wilson ◽  
...  

Author(s):  
Corey L. Campbell ◽  
Trey K. Snell ◽  
Susi Bennett ◽  
John Wyckoff ◽  
Emma K. Harris ◽  
...  

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 .


Vaccine ◽  
2019 ◽  
Vol 37 (12) ◽  
pp. 1642-1650 ◽  
Author(s):  
Z. Boumart ◽  
S. Daouam ◽  
Z. Bamouh ◽  
M. Jazouli ◽  
K.O Tadlaoui ◽  
...  

2021 ◽  
Author(s):  
Paul Wichgers Schreur ◽  
Petra Mooij ◽  
Gerrit Koopman ◽  
Babs Verstrepen ◽  
Zahra Fagrouch ◽  
...  

Abstract Rift Valley fever virus (RVFV) is an emerging mosquito-borne bunyavirus that is highly pathogenic to wild- and domesticated ruminants, camelids and humans. While animals are exclusively infected via mosquito bites, humans can also be infected via contact with tissues or blood released during the slaughtering of RVFV-infected animals. No human vaccine is available and currently commercialized veterinary vaccines do not optimally combine efficacy with safety. We previously reported the development of two novel live-attenuated RVF vaccines, created by splitting the M genome segment and deleting the major virulence determinant NSs. The vaccine candidates, referred to as the veterinary vaccine vRVFV-4s and the human vaccine hRVFV-4s, were shown to induce protective immunity in multiple species after a single vaccination. Anticipating on accidental exposure of humans to the veterinary vaccine, and to evaluate the safety of the hRVFV-4s candidate vaccine for humans, the safety of each vaccine was evaluated in the most susceptible nonhuman primate model, the common marmoset (Callithrix jacchus). Marmosets were inoculated with high doses of each vaccine and were monitored for clinical signs as well as for vaccine virus dissemination, shedding and spreading to the environment. To accurately assess the attenuation of both vaccine viruses, separate groups of marmosets were inoculated with the parent wild-type RVFV strains. Both wild-type strains induced high viremia and disseminated to primary target organs, associated with mild- to severe morbidity, while both vaccines were well tolerated with absence of dissemination and shedding, while inducing potent neutralizing antibody responses. The results of the studies support the unprecedented safety profile of both vaccines for animals and humans.


Vaccine ◽  
2013 ◽  
Vol 31 (43) ◽  
pp. 4988-4994 ◽  
Author(s):  
John C. Morrill ◽  
Richard C. Laughlin ◽  
Nandadeva Lokugamage ◽  
Jing Wu ◽  
Roberta Pugh ◽  
...  

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