Combination of Adt-O1Manisa and Ad5-boIFNλ3 induces early protective immunity against foot-and-mouth disease in cattle

Abstract

Foot-and-mouth-disease (FMD) remains the most infectious livestock disease worldwide. Although commercially available inactivated or adenovirus-vectored-vaccines (Ad5-FMD) are effective, they require 5-7 days to induce protection. Therefore, new control strategies that stimulate rapid immune responses are needed. Expression of bovine interferon λ3 using the Ad5-vector platform (Ad5-boIFNλ3) is able to delay disease in cattle, but clinical signs appear at 9 days after challenge. We hypothesized that combination of Ad5-boIFNλ3 and Ad5-FMD could induce immediate and lasting protection against FMD. Cattle were vaccinated with an Ad5-FMD, Ad5-boIFNλ3, or the combination of both, followed by challenge at three days post-immunization. All animals treated with Ad5-FMD combined with Ad5-boIFNλ3 were fully protected against FMD, despite the absence of systemic neutralizing antibodies or antiviral activity at the time of challenge. Induction of a strong cell-mediated immune response suggested that Ad5-boIFNλ3 is able to act as an adjuvant of Ad5-FMD vaccine in cattle.

The Different Tactics of Foot-and-Mouth Disease Virus to Evade Innate Immunity

“…Treated animals were completely protected against FMD and developed a significant adaptive immune response ( Moraes et al, 2003 ). More recently, similar results were described in cattle treated with a combination of Ad5-boIFN-λ3 and Ad5-O1Manisa (Ad5-O1M) against aerosol challenge with FMDV ( Diaz-San Segundo et al, 2016 ).…”

Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease

“…Using a comparable platform, a combination of Ad5-boIFN-λ3 and Ad5-FMD-O1M had a similar performance in cattle. In this experiment, complete protection was achieved after animals were exposed to FMDV by aerosol ( 42 ). Remarkably, protection of animals treated with the combination occurred despite the absence of detectable neutralizing antibodies or antiviral activity in serum at the time of the challenge ( 42 ).…”

“…In this experiment, complete protection was achieved after animals were exposed to FMDV by aerosol ( 42 ). Remarkably, protection of animals treated with the combination occurred despite the absence of detectable neutralizing antibodies or antiviral activity in serum at the time of the challenge ( 42 ). Although not proved in this study, it is possible that the remaining antiviral activity at the mucosal level was able to block FMDV replication, as described for type III IFN during rotavirus infection ( 159 ).…”

Foot-and-Mouth Disease: Optimization, Reproducibility, and Scalability of High-Yield Production of Virus-Like Particles for a Next-Generation Vaccine

“…Using the baculovirus expression system, a novel mutation in the VP2 sequence of FMDV serotype A has been reported to produce thermostable VLPs which is especially helpful in some developing countries where maintaining the cold chain for vaccine distribution can be complicated ( 14 ). Regarding viral vector vaccines using adenovirus technology for serotype A, there is already a license in the USA for emergency use in case of an outbreak ( 5 , 18 , 19 ). We have previously demonstrated that VLPs based on A2001 Argentina strain, produced using transient gene expression (TGE) in suspension-growing cells, were able to elicit an immune response in a mouse model with a 100% protection after viral challenge, a response comparable to the one obtained using a similar amount of inactivated virus ( 20 ).…”