An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern
ABSTRACT The EIAV (equine infectious anemia virus) multi-species attenuated vaccine EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA) in China in the 1970s and provided an excellent model for the study of protective immunity to lentiviruses. In this study, we compared immune responses induced by EIAV(DLV121) to immunity elicited by the virulent EIAV(LN40) strain and correlated immune responses to protection from infection. Horses were randomly grouped and inoculated with either EIAV(DLV121) (Vaccinees, Vac) or a sublethal dose of EIAV(LN40) (asymptomatic carriers, Car). Car horses became EIAV(LN40) carriers without disease symptoms. Two of the four Vac horses were protected against infection and the other two had delayed onset or reduced severity of EIA with a lethal EIAV(LN40) challenge 5.5 months post initial inoculation. In contrast, all three Car animals developed acute EIA and two succumbed to death. Specific humoral and cellular immune responses in both Vac and Car groups were evaluated for potential correlations with protection. These analyses revealed that although plasma viral loads remained between 10(3) and 10(5)copies/ml for both groups before EIAV(LN40) challenge, Vac-treated animals developed significantly higher levels of conformational dependent, Env-specific antibody, neutralizing antibody as well as significantly elevated CD4(+) T cell proliferation and IFN-γ-secreting CD8(+) T cells than those observed in EIAV(LN40) asymptomatic carriers. Further analysis of protected and unprotected cases in vaccinated horses identified that cellular response parameters and the reciprocal anti-p26-specific antibody titers closely correlated with protection against infection with the pathogenic EIAV(LN40). These data provide a better understanding of protective immunity to lentiviruses.
- SourceAvailable from: Frank Cook
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- "These have demonstrated that compared to the highly virulent EIAV Liaoning parental strain (EIAV LN ), the attenuated phenotype of EIAV FDD13 is conferred by numerous genetic substitutions distributed throughout the viral genome (Jiang et al., 2010; Liang et al., 2006; Qi et al., 2010; Shen et al., 2006; Wei et al., 2009; Zhou et al., 2007). However, while this vaccine may have protected the Chinese equine population from disease, efficacy is not complete in experimental studies particularly with heterologous EIAV challenge viruses (Meng et al., 2011; Lin et al., 2011b; Zhang et al., 2007). An alternative approach has been to attenuate EIAV by the introduction of stop codons and/or a small deletion in the S2 open reading frame of the EIAV UK infectious molecular clone (EIAV UKDS2 ) (Cook et al., 1998; Li et al., 2003; Craigo et al., 2005, 2007a). "
ABSTRACT: A detailed description of equine infectious anemia virus and host responses to it are presented. Current control and eradication of the infection are discussed with suggestions for improvements to increase their effectiveness.Veterinary Microbiology 10/2013; 167(1). DOI:10.1016/j.vetmic.2013.09.031 · 2.73 Impact Factor
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- "The plasma layer was ultracentrifuged at 100,000g for 1 h, and viral RNA in the precipitate was extracted using a QIAamp Viral RNA Mini Kit (Qiagen). The viral load in the plasma was analyzed using a previously described method (Jiang et al., 2011; Lin et al., 2011). The S2 nucleotide sequence of the infected viruses was examined at the 23, 65 and 200 dpi. "
ABSTRACT: The contribution of S2 accessory gene of equine infectious anemia virus (EIAV) to the virulence of pathogenic strains was investigated in the present study by reverse mutation of all four consensus S2 mutation sites in an attenuated EIAV proviral strain, FDDV3-8, to the corresponding sequences of a highly pathogenic strain DV117. The S2 reverse-mutated recombinant strain FDDVS2r1-2-3-4 replicated with similar kinetics to FDDV3-8 in cultivated target cells. In contrast to the results of other studies of EIAV with dysfunctional S2, reverse mutation of S2 only transiently and moderately increased the plasma viral load of inoculated horses, and induction of transient immunosuppression did not boost viral pathogenicity. In addition, inoculation of FDDVS2r1-2-3-4 induced partial protection to a challenge pathogenic virus. These results suggest that the attenuated EIAV vaccine strain with multiple mutations in multiple genes will not easily revert to a virulent phenotype.Virology 06/2013; 443(2). DOI:10.1016/j.virol.2013.05.017 · 3.28 Impact Factor
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ABSTRACT: The small ruminant lentiviruses include the prototype for the genus, visna-maedi virus (VMV) as well as caprine arthritis encephalitis virus (CAEV). Infection of sheep or goats with these viruses causes slow, progressive, inflammatory pathology in many tissues, but the most common clinical signs result from pathology in the lung, mammary gland, central nervous system and joints. This review examines replication, immunity to and pathogenesis of these viruses and highlights major differences from and similarities to some of the other lentiviruses.Comparative immunology, microbiology and infectious diseases 01/2012; 35(3):259-69. DOI:10.1016/j.cimid.2011.12.003 · 2.11 Impact Factor