A Recombinant Raccoon Poxvirus Vaccine Expressing both Yersinia pestis F1 and Truncated V Antigens Protects Animals against Lethal Plague

Abstract

In previous studies, we demonstrated in mice and prairie dogs that simultaneous administration of two recombinant raccoon poxviruses (rRCN) expressing Yersinia pestis antigens (F1 and V307—a truncated version of the V protein) provided superior protection against plague challenge compared to individual single antigen constructs. To reduce costs of vaccine production and facilitate implementation of a sylvatic plague vaccine (SPV) control program for prairie dogs, a dual antigen construct is more desirable. Here we report the construction and characterization of a novel RCN-vectored vaccine that simultaneously expresses both F1 and V307 antigens. This dual antigen vaccine provided similar levels of protection against plague in both mice and prairie dogs as compared to simultaneous administration of the two single antigen constructs and was also shown to protect mice against an F1 negative strain of Y. pestis. The equivalent safety, immunogenicity and efficacy profile of the dual RCN-F1/V307 construct warrants further evaluation in field efficacy studies in sylvatic plague endemic areas.

Responses of Juvenile Black-tailed Prairie Dogs (Cynomys ludovicianus) to a Commercially Produced Oral Plague Vaccine Delivered at Two Doses

“…As part of the transition from custom to mass production, we wanted to assure that changes in vaccine or bait production had not inadvertently compromised immunogenicity. Seroconversion in response to mass-produced vaccine baits appeared equivalent to rates reported in captive prairie dogs from previous laboratory studies (37-65%; Rocke et al 2014Rocke et al , 2015. Antibody responses to vaccine bait consumption varied among individuals ( Fig.…”

“…To test for seroconversion, we used a lateral flow assay that detects antibodies against Yersinia pestis V antigen as an index of humoral immune response to RCN-F1/V307 Rocke et al 2014Rocke et al , 2015. The assay was run as described by , with reactions scored subjectively as 0 (no visible reaction), 0-1 (very faint, an added class), 1, 2, 3, or 4.…”

Plague Vaccine Development: Current Research and Future Trends

“…The RCN-F1/V307 vaccine imparted similar degree of protection against plague not only in mice but also in prairie dogs as compared to single antigen constructs. The RCN-F1/V307 vaccine also provided protection in mice against an F1-negative strain of Y. pestis (82, 83). …”

Using Off-the-Shelf Technologies to Mass Manufacture Oral Vaccine Baits for Wildlife

“…; Abbott et al 2012). Consequently, work has been underway since the early 2000s to develop oral vaccination as a plague management tool (Abbott et al 2012;Johnson et al 2014;Rocke et al 2014). Small-scale field trials have been undertaken, but landscapescale application via mechanized delivery will be needed for biologically meaningful plague control (Johnson et al 2014;Tripp et al 2015;USFWS 2016).…”

“…Baits carrying plague vaccine (the genetically-modified raccoonpox virus strain RCN-F1/V307; Rocke et al 2014) consists mainly of distilled water, an attractant (peanut butter), and a patented, gelatin-based biopolymer matrix (Incortrixt, FoodSource Lures Corporation, Birmingham, Alabama, USA) used previously as a carrier for a recombinant vaccinia-Lyme disease vaccine (Table 1; Bhattacharya et al 2011;FoodSource 2013). Three critical features of the biopolymer matrix are: 1) live vaccines can be incorporated into the mix at a temperature low enough to assure viability; 2) the vaccine bait mixture remains malleable at this lower temperature; and 3) the vaccine remains viable through drying (Bhattacharya et al 2011;FoodSource 2013).…”