 Administrative
Core
Trans-Center Cores
| Passive Immunotherapeutics for Select Agents Host Institutions (RCE): Columbia University Medical Center (New England RCE) and the University of Texas Medical Branch (Western RCE) Co-Investigators: Description: Post exposure prophylaxis and treatment are critical challenges in the management of emerging viral diseases. Vaccines may be helpful in post exposure prophylaxis where agents replicate slowly or are initially sequestered in the periphery. However, in most instances, active immunity does not occur in a time frame wherein disease can be prevented or ameliorated. Passive immunotherapy has an established track record in management of infections with rabies, respiratory syncytial, and variola viruses. Except in rare instances where antibodies cross react with host tissues to cause disease or enhance virus uptake to accelerate progression of infection, the effects of passive immunotherapy are specific. Antivirals have been used with success in many infections, and the repertoire of effective compounds will undoubtedly improve. Nonetheless, passive immunotherapy will continue to be a significant primary or complementary line of defense. Reagents for passive immunotherapy include both convalescent serum and monoclonal antibodies (MAbs). MAbs have the advantages of defined reactivity and specificity, and enhanced safety profiles. Through previous work in pathogen detection in context of the WHO laboratory
network we enjoy access to peripheral blood lymphocytes (PBL) from victims
recovered from infection with high-risk pathogens. We have established
that PBL can be stored frozen and used for fusion several months after
collection with only insignificant loss of lg production. This Trans-RCE
project will exploit these materials and an efficient human hybridoma
fusion partner cell line (MFP-2) to produce fully human MAbs (fhMAbs)
specific for three select agents: Junin virus, Nipah virus, and Rift
Valley Fever virus. The choice of targets is based on data indicating
a potential therapeutic role for passive immunotherapy and the availability
of well-characterized clinical materials. A limited evaluation of MFP-2
has been conducted in the context of filing an IND with the FDA. Furthermore,
a commercial relationship has been established with the goal of producing
GMP grade fhMAbs for treatment of non-Hodgkin lymphomas. These factors
will enable transition of fhMAbs with antiviral activity from animal
models to clinical use. Specific aims include: 1) establish serologic
assays for screening of convalescent donor sera and human hybridoma supernatants;
2) characterize donor sera and PBL, and generate human hybridoma lines;
and 3) test neutralizing fhMAbs for protective activity in animal models. |
