Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system’s first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection—usually only 1–3 days post-treatment (dpt)—diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.. Authors: Attreed, Sarah E. [US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS)]; Silva, Christina [US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS)]; Rodriguez-Calzada, Monica [US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)]; Mogulothu, Aishwarya [US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); Univ. of Connecticut, Storrs, CT (United States)]; Abbott, Sophia [US Dept. of Agriculture (USDA), Greenport, NY (United States). Agricultural Research Service (ARS); US Dept. of Agriculture (USDA), Beltsville, MD (United States). Agricultural Research Service (ARS)]. DOE Contract: SC0014664. Subjects: biotherapeutics; 60 APPLIED LIFE SCIENCES; FMDV; IFN; IFNλ3; IL28B; PEGylation; foot-and-mouth disease; type III interferon