Safety and immunogenicity of a malignant catarrhal fever vaccine candidate expressing ovine gammaherpesvirus-2 glycoprotein B in cattle.

BACKGROUND: Infection of susceptible livestock species, including domestic cattle and American bison, with ovine gammaherpesvirus-2 (OvHV-2), a gammaherpesvirus in the genus Macavirus, can result in an often-fatal disease known as sheep-associated malignant catarrhal fever (SA-MCF). Prevention of SA-MCF via vaccination is a key goal to support livestock producers. METHODS: We assessed the safety and immunogenicity of a viral-vectored vaccine candidate consisting of a non-pathogenic recombinant alcelaphine gammaherpesvirus-1 expressing the OvHV-2 glycoprotein B (rAlHV-1/OvHV-2gB). The vaccine, formulated with an oil-in-water adjuvant, was administered intramuscularly to cattle using a prime-plus-two-boosters regimen. RESULTS: Immunized animals did not develop MCF following rAlHV-1/OvHV-2gB inoculation. The vaccine virus did not establish persistent infection, and no viral shedding was detected after any immunization. Minor and transient adverse reactions associated with the adjuvant use were observed in some animals. Immunization with rAlHV-1/OvHV-2gB significantly altered the proportions of monocytes, T- and B- cells and induced the production of IFN-γ, CCL4, and CXCL10 in blood. Following in vitro stimulation with rAlHV-1/OvHV-2gB, peripheral blood mononuclear cells from immunized animals exhibited proliferation of CD4+ and CD8+ cells, along with production of both pro- and anti-inflammatory cytokines and chemokines. OvHV-2 gB-specific antibodies were present in both blood and nasal secretions, with neutralizing antibodies detected only in blood. CONCLUSION: Despite the need for further optimization of vaccine formulation and delivery, the rAlHV-1/OvHV-2gB vaccine elicited robust immune responses, supporting further evaluation of its protective efficacy in vaccine-challenge trials.