Granulocyte-macrophage colony-stimulating factor does not increase the potency or efficacy of a foot-and-mouth disease virus subunit vaccine

Abstract

Foot-and-mouth disease (FMD) is one of the most feared diseases of livestock worldwide. Vaccination has been a very effective weapon in controlling the disease, however a number of concerns with the current vaccine including the inability of approved diagnostic tests to reliably distinguish vaccinated from infected animals and the need for high containment facilities for vaccine production, have limited its use during outbreaks in countries previously free of the disease. A number of FMD vaccine candidates have been tested and a replication-defective human adenovirus type 5 (Ad5) vector containing the FMDV capsid (P1-2A) and 3C protease coding regions has been shown to completely protect pigs against challenge with the homologous virus (FMDV A12 and A24). An Ad5-P1-2A+3C vaccine for FMDV O1 Campos (Ad5-O1C), however, only induced a low FMDV-specific neutralizing antibody response in swine potency tests. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been successfully used to stimulate the immune response in vaccine formulations against a number of diseases, including HIV, hepatitis C and B. To attempt to improve the FMDV-specific immune response induced by Ad5-O1C, we inoculated swine with Ad5-O1C and an Ad5 vector containing the gene for porcine GM-CSF (pGM-CSF). However, in the conditions used in this trial, pGM-CSF did not improve the immune response to Ad5-O1C and adversely affected the level of protection of swine challenged with homologous FMDV.

Enhanced Antiviral Activity against Foot-and-Mouth Disease Virus by a Combination of Type I and II Porcine Interferons

“…with 10 5 PFU of FMDV serotype A24, i.e., 13 50% pig infectious doses, at two sites in the heel bulb of the left rear foot (27,60). This route of challenge in swine is one recommended by the OIE (4) and has been used previously by us and many other investigators (14,15,19,45,66,75). The animals were monitored for 3 weeks after challenge.…”

Optimized Adenoviral Vector That Enhances the Assembly of FMDV O1 Virus-Like Particles in situ Increases Its Potential as Vaccine for Serotype O Viruses

“…Although recombinant adenovirus vectors have demonstrated promising capabilities as vaccine candidates for several FMDV strains ( Grubman et al, 2009 ), it has been more difficult to achieve the same results with some strains of serotype O, specifically for the epidemiologically relevant O1/Campos/Brazil/58 strain ( Caron et al, 2005 ; D’Antuono et al, 2010 ; Moraes et al, 2011 ; Romanutti et al, 2013 ; Medina et al, 2015 ).…”

“…Furthermore, the Adt-O1Manisa vector in combination with Ad5-boIFNλ3, which drives the expression of bovine IFN-λ3, completely protects cattle against homologous challenge as early as 3 dpi ( Diaz-San Segundo et al, 2016 ). On the contrary, in initial efficacy studies, the Ad5-O1/Campos/Brazil/58 (Ad5-O1C)-vectored vaccine has shown limited performance in target species such as swine ( Caron et al, 2005 ). Consequently, several strategies have been implemented to improve Ad5-O1C vaccine performance.…”

Foot-and-Mouth Disease

“…However, in these studies, three DNA inoculations were given prior to challenge. Interestingly, Caron et al (2005) found that co-delivery of an Ad5 vector encoding pGM-CSF and an Ad5-FMDV empty capsid was less effective than an empty capsid construct alone. However, studies with other immunogens indicate that the adjuvant effect of GM-CSF is most pronounced when this cytokine is co-expressed in the same vector ( Wang et al, 2002 ).…”