CRYSTAL BIOSCIENCE, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

DESCRIPTION provided by applicant We seek to capitalize on a substantial body of work that has characterized the immune responses of HIV individuals with very slow disease progression LTNP and HIV individuals who do not seroconvert despite repeated HIV exposure ESN A fraction of people in these groups produce natural anti CCR antibodies that are associated with their disease free status in longitudinal studies loss of these antibodies results in disease progression These antibodies are unique in that they bind rare CCR epitopes induce a long term downregulation of CCR on the surface of cells and can inhibit transcytosis of HIV across mucosal membranes Experimentally raised polyclonal chicken antibodies to these epitopes are even more potent than their human derived counterparts with respect to these biological activities and represent an opportunity to develop a unique product offering in the HIV AIDS arena We will use our proprietary technology to raise a panel of chicken monoclonal antibodies to these CCR epitopes and humanize the most active members of this panel for further development PUBLIC HEALTH RELEVANCE An estimated million people worldwide are now living with HIV and million are newly infected every year with a higher prevalence among women in developing countries Anti viral drugs have proven effective in allowing HIV individuals to live longer disease free lives However this success has done little to reduce the spread of HIV AIDS worldwide since it does not address HIV transmission between individuals In principle vaccines can solve this problem although many years of intense effort have not yielded a product The difficulty is to some extent due to the ability of HIV more so than other viruses to rapidly evolve and therefore evade a vaccine centric immune response that is restricted by the physical structure of the vaccine itself Furthermore it is well known that HIV individuals produce antibodies to viral proteins but generally these antibodies do not slow the progression of disease For these reasons a new strategy has emerged to identify blocking antibodies against the HIV receptors or co receptors such as CCR rather than the virus itself The receptors co receptors are native human proteins that HIV requires but does not genetically control However since receptors are andquot selfandquot proteins it is unlikely that a vaccine approach will reliably generate a vigorous response in humans The alternative is to develop potent antibodies independently in other species and use humanized versions of them in the modality of passive immunotherapy Antibodies that block HIV infection could potentially be used therapeutically in HIV individuals to reduce viral load and disease progression and could also be used prophylactically to reduce transmission between individuals if present in the appropriate mucosal tissues An innovative approach using a humanized chicken monoclonal antibody to a cryptic epitope on the HIV co receptor CCR is anticipated to yield a candidate that is superior to other CCR antibodies in preclinical or clinical development