Pongrama Ramasoota
Center of Excellent for Antibody Research (CEAR), and Department of Social & Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
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Abstract:
Dengue virus (DV) consisted of 4 serotypes, transmitted by Aedes Spp. mosquito cause Dengue disease that become one of the world’s most serious public health problems. Until present, there is no specific drug against all 4 serotypes of DV. Using Hybridoma technique to fuse peripheral blood mononuclear cell (PBMC) from dengue patients with the new myeloma Spymeg cell, two candidates anti envelope (E) protein Neutralizing human monoclonal antibodies (NhuMAbs) (1B3B9 and 1G7C2) against 4 serotypes of DV, has been the world’s first time developed at CEAR. These NhuMAbs were successfully pre-clinically tested in vitro by 95-100 % neutralized all 20 clinical DENV isolates and in vivo by significantly decreased mortality of DENV-intra-cranially infected mice and eliminated DENV (from 1010 to 0) in blood of DENV-challenged Marmosets monkey within 2 days. Under preparation to use in human, large scale production of NhuMAb using the Food and drug administration (FDA) accepted method namely Stable Chinese Hamster Ovary (CHO) cell expression, has been prepared. Until present, 7 pg/cell of NhuMAb could be produced from stable CHO cell, preparing for toxicity & safety tested and further clinical trial.
Therapeutic and diagnostic MAbs for animal viruses
Phage display technology (PDT) has been applied for producing diagnostic MAbs of animal viruses;
- Single chain variable fragment with Fragment crystalline (sCFv-Fc) MAbs with H5N1 virus specific and cross react with influenza A virus (respectively). These two MAbs could be applied for differentiation of H5N1 influenza virus from other Influenza A virus.
- sCFv-Fc MAb specific to 3ABC nonstructural protein of foot and mouth diseases virus (FMDV) that could apply for differentiation of FMDV Infected from Vaccinated Animals (DIVA).
Moreover, therapeutic canine MAb against Canine Parvovirus are under development using PDT. Some of these results will be presented.
Keyword: Therapeutic, diagnostic, MAb, Dengue virus, Influenza virus, Foot and mouth disease virus, Canine parvovirus