An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern

State Key Laboratory of Veterinary Biotechnology, Division of Livestock Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
Antiviral research (Impact Factor: 3.94). 08/2011; 92(2):292-304. DOI: 10.1016/j.antiviral.2011.08.016
Source: PubMed

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.

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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). "
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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. "
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