The effect of the TLR9 ligand CpG-oligodeoxynucleotide on the protective immune response to alcelaphine herpesvirus-1-mediated malignant catarrhal fever in cattle.

Nevi Parameswaran,Helen Todd,Mark P Dagleish,David Deane,George C Russell,Dawn M Grant,David M Haig,Kathryn Bartley

doi:10.1186/1297-9716-45-59

Nevi Parameswaran, Helen Todd + Show 6 more

Open Access

https://doi.org/10.1186/1297-9716-45-59

Copy DOI

Abstract

We wished to determine the effect of of CpG ODN adjuvant on the magnitude and duration of protective immunity against alcelaphine herpesvirus-1 (AlHV-1) malignant catarrhal fever (MCF), a fatal lymphoproliferative disease of cattle. Immunity was associated with a mucosal barrier of virus-neutralising antibody. The results showed that CpG ODN included either with emulsigen adjuvant and attenuated AlHV-1 (atAlHV-1) or alone with atAlHV-1 did not affect the overall protection from clinical disease or duration of immunity achieved using emulsigen and atAlHV-1. This is in contrast to other similar studies in cattle with BoHV-1 or cattle and pigs with various other immunogens. In addition to this, several other novel observations were made, not reported previously. Firstly, we were able to statistically verify that vaccine protection against MCF was associated with virus-neutralising antibodies (nAbs) in nasal secretions but was not associated with antibodies in blood plasma, nor with total virus-specific antibody (tAb) titres in either nasal secretions or blood plasma. Furthermore, CpG ODN alone as adjuvant did not support the generation of virus-neutralising antibodies. Secondly, there was a significant boost in tAb in animals with MCF comparing titres before and after challenge. This was not seen with protected animals. Finally, there was a strong IFN-γ response in animals with emulsigen and atAlHV-1 immunisation, as measured by IFN-γ secreting PBMC in culture (and a lack of IL-4) that was not affected by the inclusion of CpG ODN. This suggests that nAbs at the oro-nasal-pharyngeal region are important in protection against AlHV-1 MCF.

Highlights

Malignant catarrhal fever (MCF) is a usually-fatal lymphoproliferative disease of a range of ungulates including cattle, deer, bison, water buffalo and pigs [1]
We wished to determine whether the TLR9 agonist CpG oligodeoxynucleotide (CpG ODN) used with atAlHV-1 alone or in combination with Emulsigen and atAlHV-1 could improve the magnitude and duration of protective immunity afforded by our vaccine against alcelaphine herpesvirus-1 (AlHV-1) associated MCF
We show that the inclusion of CpGODN as an adjuvant was not effective in this regard, nor did it affect the degree of disease protection obtained with atALHV-1 and emulsigen alone

Summary

Introduction

Malignant catarrhal fever (MCF) is a usually-fatal lymphoproliferative disease of a range of ungulates including cattle, deer, bison, water buffalo and pigs [1]. It is caused by members of the Macavirus genus of the subfamily. There is no apparent disease in these reservoir hosts, but when the virus is transmitted to susceptible animals, MCF often ensues [1]. MCF is currently a serious problem in several parts of the world including: Indonesia, where cattle are infected by OvHV-2, North America, in farmed bison infected by OvHV-2 and in Eastern and Southern Africa where migrating wildebeest transmit AlHV-1 to cattle [1]

Objectives

Methods

Results

Discussion

Conclusion