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

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.

The efficacy of alcelaphine herpesvirus-1 (AlHV-1) immunization with the adjuvants Emulsigen ® and the monomeric TLR5 ligand FliC in zebu cattle against AlHV-1 malignant catarrhal fever induced by experimental virus challenge

“…This boosted (anamnestic) response in the infected cattle indicates that the virus managed to infect these animals, stimulating memory cells to produce more antibodies. This was consistent with previous work (Parameswaran et al, 2014, Russell et al, 2012). As 12 of these cattle died, we conclude that, if the vaccine fails to protect against infection, any antibody response that takes place after infection is not protective.…”

Wildebeest-associated malignant catarrhal fever: perspectives for integrated control of a lymphoproliferative disease of cattle in sub-Saharan Africa

“…6-month duration of protective immunity in vaccinated animals Recombinant AlHV-1 virus with ORF73 deletion Rabbit 2013 [ 50 ] ORF73-deleted recombinant virus induced a strong antibody response. Animals protected against MCF-associated pathology following lethal challenge and with virulent virus Attenuated C500 strain-AlHV-1 from serially passaged cell cultures with Emulsigen (licensed) adjuvant and unmethylated CpG oligodeoxy nucleotide (TLR9 agonist) Cattle 2014 [ 49 ] Unmethylated CpG oligodeoxynucleotide offers no additional advantage to length or level of protective immunity achieved using attenuated AlHV-1 with Emulsigen (licensed) adjuvant …”

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).…”

“…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).…”

“…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). Despite the apparent importance of the antibody response in protection against challenge, little is known regarding the identity of the targets of these antibodies.…”