Comparison of the efficacy of inactivated combination and modified-live virus vaccines against challenge infection with neuropathogenic equine herpesvirus type 1 (EHV-1).

Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Vaccine (Impact Factor: 3.49). 05/2006; 24(17):3636-45. DOI: 10.1016/j.vaccine.2006.01.062
Source: PubMed

ABSTRACT Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus of horses which causes rhinopneumonitis, abortion and myeloencephalopathy. To test the efficacy of commercial vaccines in protection against neurological EHV-1 challenge, groups of five horses were immunized with modified-live virus or an inactivated vaccine, or received placebo. Horses were challenged by aerosol with a recent virus isolate obtained from a case of paralytic EHV-1. The duration of fever decreased significantly in the modified-live virus vaccine group. Three animals in each of the inactivate and control groups showed alterations in neurological status. When compared to the inactivated vaccine, the modified-live virus vaccine induced significantly lower virus-neutralizing antibodies over the course of the study. The modified-live virus vaccine resulted in low EHV-1-specific IgG(T)/IgGa and IgG(T)/IgGb ratios, suggesting a bias towards a cytotoxic immune response. Virus shedding from the nasopharynx was almost undetectable in the modified-live virus group, and was significantly lower when compared to that in the other groups. Normalized lymphocyte viral genome copies were similar for the three groups, although animals vaccinated with the modified-live virus vaccine were qPCR-positive on fewer days when compared to those of the other groups. Based on data from neurological signs, rectal temperatures, virus isolation from nasal swabs and immune response specificity, we concluded that protection induced by the modified-live virus vaccine is superior to that induced by the inactivated combination vaccine.

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    ABSTRACT: Intra-articular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibody (NAb) and anti-capsid effector T-cells. Twelve healthy horses were assigned to treatment (rAAV2 or rAAV5) or control (saline) groups. Middle carpal joints were injected with 5 x 1011vg/joint. Synovial fluid was analyzed for changes in composition, NAb titers, immunoglobulin isotypes, pro-inflammatory cytokines and IGF-I. Serum was analyzed for antibody titers and cytokines. A T-cell re-stimulation assay was used to assess T-cell responses. Injection of rAAV2- or rAAV5-IGF-I did not induce greater inflammation compared to saline. Synovial fluid IGF-I was significantly increased in both rAAV2- and rAAV5-IGF-I joints by day 14 and remained elevated until day 56, however, rAAV5 achieved the highest concentrations . A capsid specific T-cell response was not noted although all virus treated horses had increased NAbs in serum and synovial fluid following treatment. Taken together, our data show that IA injection of rAAV2- or rAAV5-IGF-I do not incite a clinically detectable inflammatory or cell-mediated immune response and that IA gene therapy using minimally immunogenic vectors represents a clinically relevant tool for treating articular disorders including OA.