Scientific Publications by FDA Staff

J Virol 2011 May;85(9):4354-62

Chimpanzee-human monoclonal antibodies for treatment of chronic poliovirus excretors and emergency postexposure prophylaxis.

Chen Z, Chumakov K, Dragunsky E, Kouiavskaia D, Makiya M, Neverov A, Rezapkin G, Sebrell A, Purcell R

Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee/human full-length IgG (hereafter called monoclonal antibody, MAb) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine stains as well as virulent strains of poliovirus. Five MAbs were serotype-specific while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2 covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. Administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 ¿g/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 hours after virus infection provided significant protection. MAbs described here could be tested in clinical trials to determine whether they might be useful for treating of immuno-compromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case.