Env diversity-dependent protection of the attenuated equine infectious anaemia virus vaccine

Abstract

Lentiviruses harbour high genetic variability for efficient evasion from host immunity. An attenuated equine infectious anaemia (EIA) vaccine was developed decades ago in China and presented remarkably robust protection against EIA. The vaccine was recently proven to have high genomic diversity, particular in env. However, how and to what extent the high env diversity relates to immune protection remains unclear. In this study, we compared immune protections and responses of three groups of horses stimulated by the high-diversity vaccine EIAV_HD, a single molecular clone of the vaccine EIAV_LD with low env diversity, as well as a constructed vaccine strain EIAV_MD with moderate env diversity. The disparity of virus-host interactions between three env diversity-varied groups (5 horses in each group) was evaluated using clinical manifestation, pathological scores, and env-specific antibody. We found the highest titres of env antibodies (Abs) or neutralizing Abs (nAbs) in the EIAV_HD group, followed by the EIAV_MD group, and the lowest titres in the EIAV_LD group (P<0.05). The occurrence of disease/death was different between EIAV_HD group (1/0), EIAV_MD (2/2), and EIAV_LD group (4/2). A similar env diversity-related linear relationship was observed in the clinical manifestations and pathological changes. This diversity-dependent disparity in changes between the three groups was more distinct after immunosuppression, suggesting that env diversity plays an important role in protection under low host immunocompetence. In summary, inoculation with vaccines with higher genetic diversity could present broader and more efficient protection. Our findings strongly suggest that an abundance of Env antigens are required for efficient protection against lentiviruses.

Equine lentivirus counteracts SAMHD1 restriction by Rev-mediated degradation of SAMHD1 via the BECN1-dependent lysosomal pathway

“…Since macrophages with active SAMHD1 are the primary target cells of EIAV in vivo , we speculated that EIAV has evolved strategies to counteract the antiviral activity of EfSAMHD1 in these cells. To this end, eMDMs were infected with high dose (RT = 200 ng) of EIAV DLV36 (a replication-competent EIAV strain) [ 32 ] to achieve a saturated infection, and cells were harvested to detect SAMHD1 expression at 12 and 24 h post infection (hpi). Intriguingly, the expression level of EfSAMHD1 protein, but not of mRNA, gradually decreased with time following infection with EIAV ( Figure 2A,B ).…”

Immunogenicity of Novel Live Vaccine Based on an Artificial rHN20 Strain against Emerging Fowl Adenovirus 4

“…Live vaccines exhibit similar characteristics as those of natural infection by the virus, allowing them to induce strong immunity to prevent disease. Examples of successful live attenuated vaccines include those for poliovirus [22], measles virus [23], and equine infectious anemia virus [24]. Live attenuated vaccines for SARS-CoV-2 [25] and African swine fever virus [26] are also being studied.…”

A novel fully-spliced accessory gene in equine lentivirus with distinct Rev-responsive element

“…For the amplification of mat, polyadenylated RNAs were prepared from frozen horse tissues infected with EIAV LN40 using a Trizol method [51]. The tissues were homogenized in liquid nitrogen, and 1ml of Trizol regent was used to incubate each sample.…”