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.

Fig. 1.

Weekly serum 50% inhibitory concentrations (IC₅₀) against homologous EIAV_WSU5 pseudovirus for experimental and control SCID foals.

Fig. 2.

Peripheral blood platelet counts (no. of platelets/μl whole blood) (open squares) and plasma viral loads (closed circles) for SCID foals that received high-dose IgG in A2140 immune plasma (a), low-dose A2140 PPIg (b), and physiologic-dose A2140 PPIg (c to e). DPI, days post-EIAV inoculation. Stars indicate febrile days (rectal temperature of >101.5°F).

Fig. 3.

Peripheral blood platelet counts (open squares) and plasma viral loads (closed circles) for SCID foals that received a physiologic dose of A2140 PPIg (a) and healthy-horse PPIg (b), followed by challenge with EIAV_PND5. DPI, days post-EIAV inoculation. Stars indicate febrile days (rectal temperature of >101.5°F). (c) Comparison of area under the concentration-time curve (AUC) values (viral load times DPI) between EIAV-challenged control SCID foals and experimental SCID foals receiving various doses of A2140 immune plasma or PPIg. Phys-dose: Het, physiologic dose followed by heterologous EIAV challenge. For categories with at least three foals, horizontal bars indicate geometric means. Vertical error bars indicate 95% confidence intervals (CI). (d) Comparison of AUC values between EIAV-challenged control SCID foals and experimental SCID foals. Horizontal bars indicate geometric means.