Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process

Abstract

Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6-to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4 ؉ and CD8 ؉ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.

Modified-live PRRSV subtype 1 vaccine UNISTRAIN® PRRS provides a partial clinical and virological protection upon challenge with East European subtype 3 PRRSV strain Lena

“…The virus neutralizing (VN) antibodies have a crucial role in prevention of disease caused by Equine Arteritis Virus (EAV) in horses [32] and Lactate dehydrogenaseelevating virus (LDV) in mice [33]. Similarly, inhibition of the PRRSV replication can be achieved by VN antibodies [34].…”

A Pilot Study Comparing the Development of EIAV Env-Specific Antibodies Induced by DNA/Recombinant Vaccinia-Vectored Vaccines and an Attenuated Chinese EIAV Vaccine

“…Serum immunoglobulin G antibody reactivity to EIAV FDDV envelope glycoprotein was quantitatively (endpoint titer) and qualitatively (avidity index and conformation ratio) assayed using a standard ConA ELISA procedure as previously described (9), except that the coated EIAV PV was replaced with gradient-purified EIAV FDDV . The end-point titer of core p26-specific IgG was detected using a standard ELISA.…”

“…All of the sera were heat inactivated (56°C for 30 min) before the neutralization assay to inactivate infectious virus and labile serum proteins. The serum neutralizing activity against homologous (pLGFD3V), or relatively heterologous (pLGFD3Mu12V) virus strains, was assessed with a modified indirect cell ELISA-based infectious center assay method using a constant amount of pLGFD3V or pLGFD3Mu12V, and sequential twofold dilutions of serum, as previously described (9). The serum neutralizing activity against DLV34 was assessed with an RT assay as previously described (19).…”

Dynamic evolution of antibody populations in a rhesus macaque infected with attenuated simian immunodeficiency virus identified by surface plasmon resonance

“…Interestingly, while neutralizing antibody titers to the homologous virus emerge rapidly after infection, it is not until this antibody maturation is achieved that emergence of neutralizing antibody responses to the heterologous challenge virus is evident [8]. Furthermore, studies in the HIV-1 [10], SHIV [10] and equine infectious anemia virus (EIAV) [24] systems suggest that this antibody maturation process is a common property of lentiviruses [36].…”