title: Immunogenicity of a recombinant Rift Valley fever MP-12-NSm deletion vaccine candidate in calves.
abstract: The safety and immunogenicity of an authentic recombinant (ar) of the live, attenuated MP-12 Rift Valley fever (RVF) vaccine virus with a large deletion of the NSm gene in the pre-Gn region of the M RNA segment (arMP-12ΔNSm21/384) was tested in 4-6 month old Bos taurus calves. Phase I of this study evaluated the neutralizing antibody response, measured by 80% plaque reduction neutralization (PRNT80), and clinical response of calves to doses of 1 × 10(1) through 1 × 10(7) plaque forming units (PFU) administered subcutaneously (s.c.). Phase II evaluated the clinical and neutralizing antibody response of calves inoculated s.c. or intramuscularly (i.m.) with 1 × 10(3), 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384. No significant adverse clinical events were observed in the animals in these studies. Of all specimens tested, only one vaccine viral isolate was recovered and that virus retained the introduced deletion. In the Phase I study, there was no statistically significant difference in the PRNT80 response between the dosage groups though the difference in IgG response between the 1 × 10(1)PFU group and the 1 × 10(5)PFU group was statistically significant (p<0.05). The PRNT80 response of the respective dosage groups corresponded to dose of vaccine with the 1 × 10(1)PFU dose group showing the least response. The Phase II study also showed no statistically significant difference in PRNT80 response between the dosage groups though the difference in RVFV-specific IgG values was significantly increased (p<0.001) in animals inoculated i.m. with 1 × 10(4) or 1 × 10(5)PFU versus those inoculated s.c. with 1 × 10(3) or 1 × 10(5)PFU. Although the study groups were small, these data suggest that 1 × 10(4) or 1 × 10(5)PFU of arMP-12ΔNSm21/384 administered i.m. to calves will consistently stimulate a presumably protective PRNT80 response for at least 91 days post inoculation. Further studies of arMP-12ΔNSm21/384 are warranted to explore its suitability as an efficacious livestock vaccine.
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, 301 University Blvd., Room 4.142B MRB, Galveston, TX 77555-1019, USA. Electronic address: jcmorril@utmb.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Morrill
authors.forename: Richard C
authors.initials: RC
authors.lastname: Laughlin
authors.forename: Nandadeva
authors.initials: N
authors.lastname: Lokugamage
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Roberta
authors.initials: R
authors.lastname: Pugh
authors.forename: Pooja
authors.initials: P
authors.lastname: Kanani
authors.forename: L Garry
authors.initials: LG
authors.lastname: Adams
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.forename: C J
authors.initials: CJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002417:Cattle; D002418:Cattle Diseases / Q000517:prevention & control*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D009500:Neutralization Tests; D012295:Rift Valley Fever / Q000517:prevention & control / Q000662:veterinary*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology; D017384:Sequence Deletion; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: Calves; RVF MP-12-NSm deletion vaccine; Rift Valley fever; arMP-12ΔNSm21/384