Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

Abstract

Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAV UK ⌬S2 derived from a virulent proviral clone, EIAV UK ⌬S2/DU containing a second gene mutation in the virulent proviral clone, and EIAV PR ⌬S2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 10 2 to 10 3 RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAV PV strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.

Envelope variation as a primary determinant of lentiviral vaccine efficacy

“…Twenty-four ponies of mixed age and gender (SI Table 3) were inoculated intramuscularly with two 10 3 TCID 50 doses, at a 4-week interval, of EIAV D9 . The inoculated ponies were monitored daily for clinical signs of EIA, and blood samples were taken at regular intervals for standard measurements of disease, virus replication, and host immune responses, as described (23)(24)(25)35). Six months after the second vaccination, the immunized ponies were randomly divided into three challenge groups, each consisting of eight animals (SI Table 3).…”

“…We have previously reported serial studies evaluating the efficacy of an attenuated EIAV proviral vaccine containing a mutation in the viral S2 accessory gene (EIAV D9 ) (23)(24)(25). The results of these studies indicate that horses inoculated with the EIAV D9 viral vaccine were 100% protected from disease by virulent EIAV challenge.…”

Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines

“…Over the past 15 years we have evaluated a number of experimental EIAV vaccines based on inactivated whole virus, viral or recombinant envelope subunit vaccines, and various attenuated proviruses [1,2,[19][20][21][22]. The results of these vaccine trials demonstrate a remarkable breadth of efficacy, ranging from protection from detectable infection and/or disease to severe enhancement of EIAV replication and disease.…”

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AbstractWe previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV PV ) challenge [1,2]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV.

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Asociación serológica de la rinoneumonitis viral equina y la anemia infecciosa equina

“…Algunos autores han reportado previamente esta coinfección viral, con resultados contrastantes en los cuales se ha evidenciado in vivo que la infección por el HVE puede afectar la respuesta inmune al VAIE (30). Otros autores demostraron que la presencia de anticuerpos positivos para herpesvirus no modifican la tasa de replicación del VAIE (31).…”