ABSTRACT
West
Nile virus (WNV) is a mosquito-borne Flavivirus that causes
encephalitis in a subset of susceptible humans. Current treatment for
WNV infections is supportive, and no specific therapy or vaccine is
available. In this study, we directly tested the prophylactic and
therapeutic efficacy of polyclonal antibodies against WNV. Passive
administration of human gamma globulin or mouse serum prior to WNV
infection protected congenic wild-type, B-cell-deficient (μMT),
and T- and B-cell-deficient (RAG1) C57BL/6J mice. Notably, no
increased mortality due to immune enhancement was observed. Although
immune antibody completely prevented morbidity and mortality in
wild-type mice, its effect was not durable in immunocompromised mice:
many μMT and RAG1 mice eventually succumbed to
infection. Thus, antibody by itself did not completely eliminate viral
reservoirs in host tissues, consistent with an intact cellular immune
response being required for viral clearance. In therapeutic
postexposure studies, human gamma globulin partially protected against
WNV-induced mortality. In μMT mice, therapy had to be initiated
within 2 days of infection to gain a survival benefit, whereas in the
wild-type mice, therapy even 5 days after infection reduced mortality.
This time point is significant because between days 4 and 5, WNV was
detected in the brains of infected mice. Thus, passive transfer of
immune antibody improves clinical outcome even after WNV has
disseminated into the central nervous
system.
Antibody Prophylaxis and Therapy against West NileVirus Infection in Wild-Type and ImmunodeficientMice
