Humanized Monoclonal Antibodies Efficient for Neutralization of Tick-Borne Encephalitis Virus (TBEV)

Description:

TBEV causes serious illnesses from meningitis to meningo-encephalitis, totaling 3,000 cases of hospitalization in Europe and between 5,000-10,000 cases in Russia reported every year. The Far Eastern hemorrhagic TBEV strains are associated with a mortality rate (between 1-2%), higher than other strains isolated in the Siberia or Western Europe. There is a high proportion (up to 46%) of TBEV patients with temporary or permanent neurological sequelae. The number of TBEV infections has increased steadily and TBEV cases have been reported in new areas, probably reflecting an increased spread of vector tick species. Prevention of TBEV infections has been carried out in a few countries in Europe by immunization using an inactivated TBEV vaccine. The vaccine carries a high manufacturing cost and requires a regimen of multiple doses, and for this reason, vaccination is not generally carried out. The materials disclosed are humanized monoclonal antibodies derived from TBEV-neutralizing Fab antibodies isolated from infected chimpanzees by repertoire cloning. One antibody in particular, MAb 2E6, has been demonstrated to bind to and neutralize a TBEV/dengue type 4 virus chimera (via interaction with the TBEV antigenic determinants) as well as the related Langat virus. Protection against TBEV/DEN-4 infection and Langat infection has been demonstrated using animal models of infection. The antibodies disclosed, in particular MAb 2E6, have the potential for use as prophylactic and therapeutic agents against TBEV and Langat virus. Additionally, these antibodies may be suitable as diagnostic reagents for the detection of TBEV and/or Langat virus.