Protective Effects of Broadly Neutralizing Immunoglobulin against Homologous and Heterologous Equine Infectious Anemia Virus Infection in Horses with Severe Combined Immunodeficiency

Abstract

Using the equine infectious anemia virus (EIAV) lentivirus model system, we previously demonstrated protective effects of broadly neutralizing immune plasma in young horses (foals) with severe combined immunodeficiency (SCID). However, in vivo selection of a neutralization-resistant envelope variant occurred. Here, we determined the protective effects of purified immunoglobulin with more potent broadly neutralizing activity. Overall, protection correlated with the breadth and potency of neutralizing activity in vitro. Four of five SCID foals were completely protected against homologous challenge, while partial protection occurred following heterologous challenge. These results support the inclusion of broadly neutralizing antibodies in lentivirus control strategies.

Antibody Escape Kinetics of Equine Infectious Anemia Virus Infection of Horses

“…Frequent viral load measurements were taken for several weeks after virus challenge. Sequencing identified an identical neutralization-resistant viral variant (i.e., an escape mutant) in several NAb-infused horses (6,7). This variant was absent in control-infused horses.…”

“…Immune escape, and particularly antibody escape, is not well understood, partly because appropriate data sets that yield quantitative estimates of escape kinetics are rare (5). Recently, studies of horses infected with equine infectious anemia virus (EIAV) have successfully documented antibody escape (6,7), thus providing a unique data set to examine the kinetics of antibody escape in a lentiviral infection. The goal of the present study was to estimate the strength of antibody pressure in this infection by determining how rapidly the virus escapes from the antibody response.…”

“…Viral load measurements were taken beginning on the initial day of infection through peak infection with sampling every few days. As part of previous studies (6,7), horses A2245, A2247, H707, and H713 received infusions of irrelevant control antibodies from an uninfected immunocompetent horse; horses A2239, A2240, and H703 received infusions of NAbs from a persistently infected immunocompetent horse; horse H715 received lowdose infusions of NAbs; and horse A2274 received infusions of NAbs followed by heterologous virus challenge. Horse H727 served as the control for the heterologous challenge and received infusions of irrelevant control antibodies from an uninfected immunocompetent horse.…”

“…We employed mathematical modeling and the data from EIAV infections of SCID horses (6,7) to calculate the rate of viral escape due to antibody pressure. We also estimated the growth rates of wild-type and mutant viruses, the rate of antibody blocking of wild-type virus, the fitness cost of antibody escape, and the mutant growth advantage.…”

“…We aimed to determine the values of these parameters by comparison with the equine data (Table 1). Plasma viral load from 10 SCID horses experimentally infected with EIAV was measured by real-time quantitative RT-PCR, as described previously (6,7). Viral load measurements were taken beginning on the initial day of infection through peak infection with sampling every few days.…”