Duration of protective immunity and antibody responses in cattle immunised against alcelaphine herpesvirus-1-induced malignant catarrhal fever

Abstract

Protection of cattle from alcelaphine herpesvirus-1 (AlHV-1)-induced malignant catarrhal fever (MCF) has been described previously, using an attenuated virus vaccine in an unlicensed adjuvant. The vaccine was hypothesised to induce a protective barrier of virus-neutralising antibody in the oro-nasal region, supported by the observation of high titre neutralising antibodies in nasal secretions of protected animals. Here we describe further analysis of this vaccine strategy, studying the effectiveness of the vaccine formulated with a licensed adjuvant; the duration of immunity induced; and the virus-specific antibody responses in plasma and nasal secretions. The results presented here show that the attenuated AlHV-1 vaccine in a licensed adjuvant protected cattle from fatal intranasal challenge with pathogenic AlHV-1 at three or six months. In addition, animals protected from MCF had significantly higher initial anti-viral antibody titres than animals that succumbed to disease; and these antibody titres remained relatively stable after challenge, while titres in vaccinated animals with MCF increased significantly prior to the onset of clinical disease. These data support the view that a mucosal barrier of neutralising antibody blocks infection of vaccinated animals and suggests that the magnitude of the initial response may correlate with long-term protection. Interestingly, the high titre virus-neutralising antibody responses seen in animals that succumbed to MCF after vaccination were not protective.

The Pathology of Malignant Catarrhal Fever, With an Emphasis on Ovine Herpesvirus 2

“…25,118 Currently, there is renewed interest in vaccination for this group of viruses, a goal long thought out of reach due to discouraging results in the 1970s and 1980s. 32,75,118,125,126 It is now clear that some dead-end host species recover, 92,93,153 corroborating clinical suspicions from the late 1920s and early 1930s that MCF is not invariably fatal. Important differences exist between the ecology of sheep-and wildebeest-associated MCF.…”

Identification of immuno-reactive capsid proteins of malignant catarrhal fever viruses

“…The antibody titre in protected animals did not rise significantly after challenge suggesting that virus was unable to penetrate the mucosal barrier and boost the response. Conversely, in vaccinated animals that succumbed to MCF, the antibody titre rose significantly after challenge, indicating successful virus entry and stimulation of an anamnestic response that was not protective (Russell et al, 2012;Parameswaran et al, 2014). This study also showed that in a few animals, protection from MCF was found despite the generation of little or no neutralising antibody, suggesting that immune mechanisms other than virus-neutralising antibody may influence protection from AlHV-1 (Parameswaran et al, 2014).…”

“…AlHV-1 that has been propagated in culture for up to five passages is capable of inducing MCF in susceptible species such as cattle and certain laboratory animals but further laboratory passage of the virus leads to the attenuation of pathogenicity and is accompanied by rearrangements of the virus genome (Wright et al, 2003). Attenuated strains of AlHV-1 have been used as the basis for all serological tests for MCF described to date Li et al, 1994;Russell et al, 2012) and the attenuated strain of AlHV-1 C500 at passage >1000 has been used as a candidate vaccine that could protect cattle from intranasal challenge with a fatal dose of pathogenic AlHV-1 in experimental trials Russell et al, 2012). In susceptible species, primary, transient viral replication appears to occur within lung epithelium, after which the virus disseminates systemically .…”

“…It has been suggested that establishment of a protective mucosal immune barrier in the naso-pharyngeal region is critical for vaccine protection against MCF infection Parameswaran et al, 2014). A recent vaccination study has shown that a high-titre virus-specific antibody response prior to challenge correlates with protection (Russell et al, 2012). The antibody titre in protected animals did not rise significantly after challenge suggesting that virus was unable to penetrate the mucosal barrier and boost the response.…”

Biochemical and proteomic investigation of bovine nasal secretion

“…Many deer die within 48 hr of the first clinical signs and affected bison generally die within 3 days (O'Toole et al, 2002). In contrast, mortality seen in cattle can occur within a few days or weeks after the first clinical signs (Russell et al, 2012).…”