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

Sarah E Attreed; Christina Silva; Monica Rodriguez-Calzada; Aishwarya Mogulothu; Sophia Abbott; Paul Azzinaro; Peter Canning; Lillian Skidmore; Jay Nelson; Nick Knudsen; Gisselle N Medina; Teresa de Los Santos; Fayna Díaz-San Segundo

doi:10.3389/fmicb.2024.1360397

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

Front Microbiol. 2024 Apr 4:15:1360397. doi: 10.3389/fmicb.2024.1360397. eCollection 2024.

Authors

Sarah E Attreed¹, Christina Silva¹, Monica Rodriguez-Calzada^{1

2}, Aishwarya Mogulothu^{1

3}, Sophia Abbott^{1

4}, Paul Azzinaro¹, Peter Canning⁵, Lillian Skidmore⁶, Jay Nelson⁶, Nick Knudsen⁶, Gisselle N Medina^{1

7}, Teresa de Los Santos¹, Fayna Díaz-San Segundo^{1

8}

Affiliations

¹ Plum Island Animal Disease Center, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, NY, United States.
² Oak Ridge Institute for Science and Education Plum Island Animal Disease Center Research Participation Program, Oak Ridge, TN, United States.
³ Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States.
⁴ Animal Biosciences and Biotechnology Laboratory, Northeast Area, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD, United States.
⁵ VetBio Partners, LLC., Carmel, IN, United States.
⁶ Ambrx Biopharma, Inc., La Jolla, CA, United States.
⁷ National Bio-and Agro-Defense Facility, Plains Area, Agricultural Research Service, U.S. Department of Agriculture, Manhattan, KS, United States.
⁸ Office of Biodefense, Research Resources and Translational Research, National Institute of Allergy and Infectious Disease, Rockville, MD, United States.

Abstract

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.

Keywords: FMDV; IFN; IFNλ3; IL28B; PEGylation; biotherapeutics; foot-and-mouth disease; type III interferon.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Agricultural Research Service (ARS)-CRIS Project 8064-32000-061, an ARS Innovation Fund support grant (Award# 092-0142-020, 042) along with a Material Transfer Research Agreement (MTRA) with Ambrx Biopharma, Inc. (MTRA#58-8064-9-014). During the time of the study and/or manuscript writing, SaA and MR-C were recipients of a Plum Island Animal Disease Center Research Participation Program fellowship, administered by the Oak Ridge Institute for Science and Education (ORISE) through and interagency agreement with the U.S. Department of Energy.