DEVELOPMENT OF VACV NEUTRALIZING ANTIBODIES MIXTURE AS A THERAPEUTIC DRUG FOR SMALLPOX VACCINE ADVERSE REACTIONS

Smallpox vaccine consists of live vaccinia (VACV) which was used worldwide to eradicate smallpox. Currently the vaccine is used to vaccinate laboratory workers with poxviruses and stockpiled to accommodate smallpox reemergence. The vaccine is associated with rare but severe adverse reactions. Plasma derived vaccinia immune globulins (VIG) is an FDA approved drug isolated from vaccinated donors for the treatment of these adverse reactions. However, it has a limited potency, limited supply and it is a human variable product. The aim of this study was to develop an improved mixture of recombinant antibodies as an alternative to VIG. To that aim, we have used the phage display technology for the isolation of human monoclonal antibodies derived from non human primates, vaccinated with live VACV. We have also developed a high throughput neutralization assay tool for both VACV infected forms: MV and EV that will enable us to evaluate the neutralization efficacy of large number of monoclonal antibodies preparations, one by one in various combinations and with limited amounts of purified preparations. We show here that using this technology, we could detect highly potent neutralizing antibodies against VACV isolated from the phage library that could potentially replace the commercial available VIG.