In addition, NDV has been used as an oncolytic agent against bovine papillomatosis in cattle and has been shown to be safe in repeated inoculations [38]. NDV shares only a low level of amino acid sequence identity with bovine paramyxoviruses and is antigenically distinct, suggesting that the entire bovine population would be susceptible to infection with a NDV vectored vaccine. Thus prior immunity against common bovine viruses should not affect the replication and immunogenicity of the vector. Recently, we have shown that IN and IT inoculation of calves with the lentogenic NDV strain LaSota resulted in an asymptomatic infection of the respiratory

learn more tract with induction of mucosal and systemic antibody responses against NDV [29]. Therefore, NDV is an attractive vector for bovine pathogens for which vaccines are not available or need improvement. In this study, for the first time, we have evaluated the potential of NDV as a vaccine vector for bovine use. Primary

infection by BHV-1 occurs at mucosal surfaces via contact or aerosol transmission. Mucosal infection with BHV-1 engenders mucosal antibodies and resistance to primary infection [41]. It has been demonstrated previously that the level of protection against BHV-1 correlated with the magnitude of the mucosal antibody response MEK inhibitor clinical trial [9], [42] and [43]. The envelope of BHV-1 has three major surface glycoproteins, namely the gB, gC, and gD glycoproteins. Respiratory infection by BHV-1 requires gD for attachment and penetration of the virus into cells [44]. Monoclonal antibodies against gD Thymidine kinase prevent infection, and thus gD is an independent neutralization antigen [45] and [46]. Native or recombinant BHV-1 gD has been shown to induce neutralizing antibodies in serum and protection from challenge [1] and [5]. Previously we have shown that NDV is capable of infecting calves through the respiratory route and induced both humoral and mucosal antibodies without causing any symptomatic disease [29]. Therefore, immunization

with an NDV vector by the respiratory route would provide for direct stimulation of immunity at the primary site of infection. A single intranasal immunization of calves with NDV-vectored vaccines based on the avirulent LaSota strain induced gD-specific IgG and IgA responses in serum and nasal secretions, respectively. The immune response produced by a single immunization with the rLaSota/gDFL or rLaSota/gDF vaccine was not sufficient to prevent BHV-1 shedding following challenge, but the virus titers and duration of shedding were reduced as compared to the control group. The increase of gD-specific IgG in vaccinated calves suggested that the gD expressed by rLaSota/gDFL or rLaSota/gDF vaccines was sufficient to prime the antigen specific IgG.