scholarly journals Development of an Empty Viral Capsid Vaccine against Foot and Mouth Disease

Author(s):  
Marvin J. Grubman ◽  
Yehuda Stram ◽  
Peter W. Mason ◽  
Hagai Yadin

Foot-and-mouth disease (FMD), a highly infectious viral disease of cloven-hoofed animals, is economically the most important disease of domestic animals. Although inactivated FMD vaccines have been succesfully used as part of comprehensive eradication programs in Western Europe, there are a number of concerns about their safety. In this proposal, we have attempted to develop a new generation of FMD vaccines that addresses these concerns. Specifically we have cloned the region of the viral genome coding for the structural proteins and the proteinase responsible for processing of the structural protein precursor into both a DNA vector and a replication-deficient human adenovirus. We have demonstrated the induction of an FMDV-specific immune response and a neutralizing antibody response with the DNA vectors in mice, but preliminary potency and efficacy studies in swine are variable. However, the adenovirus vector induces a significant and long-lived neutralizing antibody response in mice and most importantly a neutralizing and protective response in swine. These results suggest that the empty capsid approach is a potential alternative to the current vaccination strategy.

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0157435 ◽  
Author(s):  
Maria Gullberg ◽  
Louise Lohse ◽  
Anette Bøtner ◽  
Gerald M. McInerney ◽  
Alison Burman ◽  
...  

2015 ◽  
Vol 23 (2) ◽  
pp. 125-136 ◽  
Author(s):  
Gisselle N. Medina ◽  
Nestor Montiel ◽  
Fayna Diaz-San Segundo ◽  
Diego Sturza ◽  
Elizabeth Ramirez-Medina ◽  
...  

ABSTRACTNovel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+and CD8+gamma interferon (IFN-γ)+cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle.


PLoS ONE ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. e0173327
Author(s):  
Maria Gullberg ◽  
Louise Lohse ◽  
Anette Bøtner ◽  
Gerald M. McInerney ◽  
Alison Burman ◽  
...  

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 996
Author(s):  
Ntungufhadzeni M. Rathogwa ◽  
Katherine A. Scott ◽  
Pamela Opperman ◽  
Jacques Theron ◽  
Francois F. Maree

The effective control of foot-and-mouth disease (FMD) relies strongly on the separation of susceptible and infected livestock or susceptible livestock and persistently infected wildlife, vaccination, and veterinary sanitary measures. Vaccines affording protection against multiple serotypes for longer than six months and that are less reliant on the cold chain during handling are urgently needed for the effective control of FMD in endemic regions. Although much effort has been devoted to improving the immune responses elicited through the use of modern adjuvants, their efficacy is dependent on the formulation recipe, target species and administration route. Here we compared and evaluated the efficacy of two adjuvant formulations in combination with a structurally stabilized SAT2 vaccine antigen, designed to have improved thermostability, antigen shelf-life and longevity of antibody response. Protection mediated by the Montanide ISA 206B-adjuvanted or Quil-A Saponin-adjuvanted SAT2 vaccines were comparable. The Montanide ISA 206B-adjuvanted vaccine elicited a higher SAT2 neutralizing antibody response and three times higher levels of systemic IFN-γ responses at 14- and 28-days post-vaccination (dpv) were observed compared to the Quil-A Saponin-adjuvanted vaccine group. Interestingly, serum antibodies from the immunized animals reacted similarly to the parental vaccine virus and viruses containing mutations in the VP2 protein that simulate antigenic drift in nature.


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