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Human vaccine candidate (DDVax) development against Rift Valley Fever: dissemination safety studies in mosquitoes
  • +9
  • Corey L. Campbell,
  • Trey K. Snell,
  • Susi Bennett,
  • John Wyckoff,
  • Emma K. Harris,
  • Daniel A. Hartman,
  • Elena Lian,
  • Brian Bird,
  • Mark D. Stenglein,
  • Richard Bowen,
  • Rebekah Kading,
  • * Darragh
Corey L. Campbell
Colorado State University

Corresponding Author:[email protected]

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Trey K. Snell
Colorado State University
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Susi Bennett
Colorado State University
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John Wyckoff
BioMARC Infectious Diseases Research Center CSU
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Emma K. Harris
Colorado State University
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Daniel A. Hartman
Colorado State University
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Elena Lian
Colorado State University
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Brian Bird
University of California Davis School of Veterinary Medicine
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Mark D. Stenglein
Colorado State University
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Richard Bowen
Colorado State University
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Rebekah Kading
Colorado State University
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* Darragh
BioMARC Infectious Diseases Research Center CSU
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Abstract

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 10 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 .
19 Aug 2021Submitted to Transboundary and Emerging Diseases
20 Aug 2021Submission Checks Completed
20 Aug 2021Assigned to Editor
22 Aug 2021Reviewer(s) Assigned
10 Sep 2021Review(s) Completed, Editorial Evaluation Pending
12 Sep 2021Editorial Decision: Revise Major
21 Nov 20211st Revision Received
21 Nov 2021Submission Checks Completed
21 Nov 2021Assigned to Editor
30 Nov 2021Review(s) Completed, Editorial Evaluation Pending
30 Nov 2021Editorial Decision: Accept