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178 Evaluation of Genetically Engineered Live-Attenuated Vaccines for Equine Infectious Anemia Virus (EIAV)
R. Montelaro1, F. Li*1, B. Puffer1, K. Hennessy2, and C. Issel3
1Univ. of Pittsburgh, PA, USA; 2Intervet, Inc., Merriam, KS, USA; and 3Univ. of Kentucky, Lexington, USA
Background: As an animal lentivirus model for AIDS vaccine development, we have evaluated the immunogenicity and protective efficacy of 3 different live-attenuated EIAV vaccine strains containing engineered genetic mutations that markedly down-regulate viral replication in horses.
Methods: Two of the attenuated EIAV strains, EIAVUK?S2 and EIAVPr?S2, contained deletions in the S2 accessory gene of a pathogenic (UK) or avirulent (Pr) proviral molecular clone, respectively. The third vaccine strain, EIAVUK?S2?DU contained an additional mutation in the viral dUTPase gene that is required for efficient replication in equine macrophages, the natural target in vivo. Inoculation of groups of horses (6(8 each) with each attenuated vaccine strain resulted in very low level viral replication (<103 RNA copies/ml), but robust virus-specific cellular and humoral immune responses by 6 months post inoculation. Although the 3 vaccine strains displayed similar replication and immunogenic properties, they yielded different levels of protection from multiple I.V. inoculations (3 ( 10 HID) with our standard challenge strain, EIAVPV, under conditions that result in 100% infection and disease in naïve horses. Neither the EIAVPr?S2 nor the EIAVUK?S2?DU vaccine prevented infection by the virus challenge, but these immunizations did protect against the development of disease in 7/8 and 6/8 inoculated horses, respectively. In contrast, the EIAVUK vaccine produced apparent sterilizing immunity; there was no evidence of disease or infection by the challenge virus in 6/6 immunized animals. In a separate vaccine trial with the EIAVUK?S2 vaccine, apparent sterilizing immunity was also demonstrated in 3/3 immunized ponies challenged with 300 HID of the I.V. virus challenge.
Results: These data demonstrate for the first time the capacity of an attenuated live EIAV vaccine to provide protection from multiple exposure and high levels of virus challenge, but also indicate the marked influence of even subtle changes in vaccine virus envelope specificity and genetic attenuations on protective efficacy.
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