There are no FDA licensed
vaccines or
therapeutics for Venezuelan equine encephalitis virus (VEEV) which causes a debilitating acute febrile illness in humans that can progress to
encephalitis. Previous studies demonstrated that murine and macaque
monoclonal antibodies (mAbs) provide prophylactic and therapeutic efficacy against VEEV peripheral and
aerosol challenge in mice. Additionally, humanized versions of two neutralizing mAbs specific for the E2
glycoprotein, 1A3B-7 and 1A4A-1, administered singly protected mice against aerosolized VEEV. However, no studies have demonstrated protection in nonhuman primate (NHP) models of VEEV
infection. Here, we evaluated a chimeric antibody 1A3B-7 (c1A3B-7) containing mouse variable regions on a human
IgG framework and a humanized antibody 1A4A-1 containing a serum half-life extension modification (Hu-1A4A-1-YTE) for their post-exposure efficacy in NHPs exposed to aerosolized VEEV. Approximately 24 hours after exposure, NHPs were administered a single bolus intravenous mAb. Control NHPs had typical
biomarkers of VEEV
infection including measurable
viremia,
fever, and
lymphopenia. In contrast, c1A3B-7 treated NHPs had significant reductions in
viremia and
lymphopenia and on average approximately 50% reduction in
fever. Although not statistically significant, Hu-1A4A-1-YTE administration did result in reductions in
viremia and
fever duration. Delay of treatment with c1A3B-7 to 48 hours post-exposure still provided NHPs protection from severe VEE disease through reductions in
viremia and
fever. These results demonstrate that post-exposure administration of c1A3B-7 protected macaques from development of severe VEE disease even when administered 48 hours following
aerosol exposure and describe the first evaluations of VEEV-specific mAbs for post-exposure prophylactic use in NHPs. Viral mutations were identified in one NHP after c1A3B-7 treatment administered 24 hrs after virus exposure. This suggests that a cocktail-based
therapy, or an alternative mAb against an
epitope that cannot mutate without resulting in loss of viral fitness may be necessary for a highly effective therapeutic.