Evaluation of recombinant Newcastle disease viruses (NDV) as candidate vaccine delivery vectors for rotavirus VP7 and NSP4

[摘要] Rotavirus (RV) is one of the leading causes of neonatal calf diarrhoea (NCD), a disease which has a devastating impact on the agricultural industry due to high morbidity and mortality rates. There is also mounting evidence for interspecies transmission of RV from animals to humans which contribute to strain diversity and stresses the need for a One Health approach in RV control. The development of the Newcastle disease virus (NDV) reverse-genetic system has opened up ways in which attenuated NDV La Sota can be used as a vaccine vector in non-avian species. Natural host-range restrictions and an inability to combat the host's innate immunity, has rendered the use of attenuated NDV in mammals inherently safe. Since NDV is antigenically distinct from common animal pathogens, it will not be recognized by a pre-existing immunity. By utilizing the genome sequence of a South African bovine group A RV, recombinant NDVs were engineered to express RV outer capsid protein, VP7, and enterotoxin protein, NSP4. Protein expression was confirmed by immunofluorescent monolayer assay (IFMA) and western blot analysis. The ability of the recombinant NDVs to elicit humoral immune responses were evaluated in laboratory-bred adult mice. Vaccination was done twice via the oronasal or subcutaneous route and blood samples were collected 3 weeks after each immunization. The serums of the vaccinated mice were analysed for RV-related humoral immune responses by IFMAs and virus neutralization assays. Immune responses induced in mice dosed with rNDV-VP7 were suboptimal and lacked neutralizing ability for either mode of administration. This might be explained by a loss of antigenic determinates resembling those of the native protein when VP7 is expressed in the absence of other RV proteins. Immune responses induced in rNDV-NSP4 vaccinated mice were promising and correlated well with an oronasal route of administration. It has been reported that antibodies directed against NSP4 have the capacity to neutralize the enterotoxicity of the protein and reduce the severity of RV-related diarrhoea during the early stages of infection. In addition, NSP4 has been shown to have adjuvant properties. This study indicates the potential of rNDV-NSP4 in a combination vaccine which might help to prevent diarrhoea in new-born calves and increase the immune responses towards a co-administered antigen.

[发布机构] University of the Free State