BoHV-1-Vectored BVDV-2 Subunit Vaccine Induces BVDV Cross-Reactive Cellular Immune Responses and Protects against BVDV-2 Challenge.

Shafiqul I Chowdhury,Selvaraj Pavulraj,Katrin Pannhorst,Neha Sangewar,Rhett W Stout,Waithaka Mwangi,Xue Wen,Daniel B Paulsen

doi:10.3390/vaccines9010046

Shafiqul I Chowdhury, Selvaraj Pavulraj + Show 6 more

Open Access

https://doi.org/10.3390/vaccines9010046

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Journal: Vaccines	Publication Date: Jan 13, 2021
Citations: 15	License type: CC BY 4.0

Affiliation: Louisiana State University, Kansas State University

Abstract

The bovine respiratory disease complex (BRDC) remains a major problem for both beef and dairy cattle industries worldwide. BRDC frequently involves an initial viral respiratory infection resulting in immunosuppression, which creates a favorable condition for fatal secondary bacterial infection. Current polyvalent modified live vaccines against bovine herpesvirus type 1(BoHV-1) and bovine viral diarrhea virus (BVDV) have limitations concerning their safety and efficacy. To address these shortcomings and safety issues, we have constructed a quadruple gene mutated BoHV-1 vaccine vector (BoHV-1 QMV), which expresses BVDV type 2, chimeric E2 and Flag-tagged Erns-fused with bovine granulocyte monocyte colony-stimulating factor (GM-CSF) designated here as QMV-BVD2*. Here we compared the safety, immunogenicity, and protective efficacy of QMV-BVD2* vaccination in calves against BVDV-2 with Zoetis Bovi-shield Gold 3 trivalent (BoHV-1, BVDV types 1 and 2) vaccine. The QMV-BVD2* prototype subunit vaccine induced the BoHV-1 and BVDV-2 neutralizing antibody responses along with BVDV-1 and -2 cross-reactive cellular immune responses. Moreover, after a virulent BVDV-2 challenge, the QMV-BVD2* prototype subunit vaccine conferred a more rapid recall BVDV-2-specific neutralizing antibody response and considerably better recall BVDV types 1 and 2-cross protective cellular immune responses than that of the Zoetis Bovi-shield Gold 3.

Highlights

The bovine respiratory disease complex (BRDC) remains a major economic problem for both beef and dairy cattle industries in North America and worldwide due to calf mortality, treatment expenses, and additional labor incurred
The expression of chimeric bovine viral diarrhea virus (BVDV)–2 E2 antigen and Flag–tagged Erns–GM–CSF in QMV–BVD2*–infected cell lysates was verified by SDS–PAGE/Western immunoblotting
Even though the same amounts of proteins were loaded in the two duplicate gels (2.8 in M & M), the amount of Flag–tagged chimeric Erns–GM–CSF protein detected by the anti–Flag antibody, on the Western immunoblot (Figure 4A) was considerably less compared with that of chimeric E2 recognized by the Anti–BVDV–2 E2–specific monoclonal antibody (mAb)

Summary

Introduction

The bovine respiratory disease complex (BRDC) remains a major economic problem for both beef and dairy cattle industries in North America and worldwide due to calf mortality, treatment expenses, and additional labor incurred. The United States Department of Agriculture National Animal Health Monitoring Service reported that BRD affects 12.4% of calves during the pre-weaning period, resulting in 22.5% calf mortality. The detrimental economic impact of BRD on the American beef industry is even larger than in the dairy industry. It is the most expensive disease affecting feedlot cattle, and it is estimated to cause losses of approximately one billion dollars per year in the USA [2]. The initial viral respiratory infection creates a favorable condition for colonization of the lungs, usually by M. haemolytica, resulting in severe pneumonia and death of infected cattle, especially in the feedlots [3]

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