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Immunogenicity of a recombinant Rift Valley fever MP-12-NSm deletion vaccine candidate in calves

Author:
Morrill, John C., Laughlin, Richard C., Lokugamage, Nandadeva, Wu, Jing, Pugh, Roberta, Kanani, Pooja, Adams, L. Garry, Makino, Shinji, Peters, C.J.
Source:
Vaccine 2013 v.31 no.43 pp. 4988-4994
ISSN:
0264-410X
Subject:
RNA, Rift Valley fever, calves, genes, immune response, immunoglobulin G, neutralization, neutralizing antibodies, viral vaccines, viruses
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 1×101 through 1×107 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 1×103, 1×104 or 1×105PFU 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 1×101PFU group and the 1×105PFU group was statistically significant (p<0.05). The PRNT80 response of the respective dosage groups corresponded to dose of vaccine with the 1×101PFU 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 1×104 or 1×105PFU versus those inoculated s.c. with 1×103 or 1×105PFU. Although the study groups were small, these data suggest that 1×104 or 1×105PFU 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.
Agid:
1113185