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Principal Investigator: DARRICK Albert CARTER
Organization: PAI LIFE SCIENCES, INC.
Fiscal Year: 2024
Award: $995,460
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
Lymphatic filariasis (LF) is one of only a small number of diseases classified as potentially
eradicable. In 1997, the World Health Assembly passed a resolution to eliminate LF as a public
health problem and the approach involved yearly concurrent mass drug administration (MDA)
to the at-risk population in 52 countries. According to the WHO, about 856 million people are
at-risk of acquiring LF and need annual MDA treatment. After over 17 years of MDA to the at-
risk population and spending several billion dollars, the incidence of LF infection has not
significantly declined. This is likely due to subject non-compliance and lack of effectiveness of
the drugs against the adult parasites living within the lymphatic system. Thus, reliance on the
drug therapy approach alone is ineffective in limiting disease transmission. In fact,
chemotherapy only treats current infections and does not prevent future re-infections leaving
the patients susceptible to the disease. Several recent studies show that the disease is re-
emerging in several parts of the world. Therefore, there is a critical need for developing an
effective prophylactic vaccine that can support the current MDA approach for preventing
disease transmission and total elimination of the disease from endemic regions.
Unlike most other infectious organisms such as viruses, bacteria or protozoa, the lymphatic
filarial parasites do not replicate within their definitive hosts. Therefore, the prophylactic
vaccine against LF need not induce sterilizing immunity to be effective for controlling the
infection. In fact, the World Health Organization (WHO) has determined that helminth vaccines
that can prevent worm establishment by 50% will be effective in reducing overall morbidity and
mortality.
Over the last 2 decades, several vaccine candidates were identified and tested for their
therapeutic potential against LF in rodent models. However, none of these candidates
advanced beyond rodent testing - partially because of poor protection and/or lack of resources
to advance the technology. We have developed and established the first successful multivalent
recombinant fusion protein vaccine (BmHAXT) for the prophylaxis of LF. The vaccine gives
close to sterile immunity in rodents and significant protection in non-human primates (70%)
when given along with a TLR4 agonist adjuvant. BmHAXT is now ready to move clinical
development. Thus, the major focus of this project is to perform the remaining IND enabling
activities including (Aim 1) the CMC activities required for regulatory submission and
demonstrating stability of the human use product, (Aim 2) the preclinical animal testing to
confirm that the newly manufactured LFguard™ vaccine maintains its potency in experimental
animal models and that it is safe in a GLP toxicology study, and finally, (Aim 3) write the clinical
and supporting documents and submitting the IND.
Terms: <21+ years old><Adjuvant><Adult><Adult Human><Affect><Agonist><Alum Adjuvant><Animal Model><Animal Models and Related Studies><Animal Testing><Antigens><Assay><Bacteria><Bancroftian Elephantiasis><Bioassay><Biologic Sciences><Biological><Biological Assay><Biological Sciences><Bioscience><Booklets><Brochures><Brugia malayi><Chemistry><Chronic><Clinical><Clinical Research><Clinical Study><Clinical Trials><Contracting Opportunities><Contracts><Country><Coupled><Culicidae><Cyclic GMP><DALY><Development><Disease><Disorder><Domestic Rabbit><Drug Therapy><Drugs><Effectiveness><Endemic Diseases><Engineering><Experimental Animal Model><Filaria bancrofti><Filaria sanguinis hominis><Filarial Elephantiases><Formulation><Future><Gerbils><Grant><Groups at risk><Guanosine Cyclic Monophosphate><Helminths><Homolog of Drosophila TOLL><Human><Immunity><Incidence><Individual><Infection><Infection Control><Infectious Agent><Interruption><Investigators><Jird><Larva><Licensing><Life Sciences><Lymph System><Lymphatic><Lymphatic Filariasis><Lymphatic Network><Lymphatic System><Lymphatic System Reticuloendothelial System><Lymphedema><M mulatta><M. mulatta><Macaca mulatta><Medication><Merione><Mice><Mice Mammals><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Mosquitoes><Murine><Mus><NIH><National Institutes of Health><Oryctolagus cuniculus><Pamphlets><Parasites><Parasitic Worms><Pathology><Patients><People at risk><Persons><Persons at risk><Pharmaceutical Preparations><Pharmacotherapy><Phase><Populations at Risk><Predisposition><Preventative Immunization><Preventative vaccination><Preventative vaccine><Preventive Immunization><Preventive vaccination><Preventive vaccine><Prophylactic immunization><Prophylactic treatment><Prophylactic vaccination><Prophylactic vaccine><Prophylaxis><Proteins><Protocol><Protocols documentation><Protozoa><Protozoal><Public Health><Rabbits><Rabbits Mammals><Recombinant Fusion Proteins><Reporting><Research><Research Personnel><Research Resources><Researchers><Resolution><Resources><Rhesus Macaque><Rhesus Monkey><Risk><Rodent><Rodent Model><Rodentia><Rodents Mammals><Running><SBIR><Safety><Small Business Innovation Research><Small Business Innovation Research Grant><Sterility><Susceptibility><TLR4><TLR4 gene><Technology><Testing><Therapeutic><Toll Homologue><Toxicology><Transmission><United States National Institutes of Health><Vaccines><Virus><World Health><World Health Organization><Writing><Wuchereria bancrofti><adulthood><alum><aluminum sulfate><biologic><cGMP><cell bank><chemotherapy><clinical development><communicable disease transmission><design><designing><developmental><disability-adjusted life years><disease classification><disease transmission><disorder classification><drug detection><drug testing><drug treatment><drug/agent><first in man><first-in-human><functional mimics><global health><immune response to vaccination><immune response to vaccines><immunogen><infectious disease transmission><infectious organism><lymph edema><lymphatic edema><manufacture><model of animal><mortality><neglected tropical diseases><non-compliance><non-compliant><non-human primate><noncompliance><noncompliant><nonhuman primate><nosology><novel><phase 2 study><phase II study><physical disability><physically disabled><physically handicapped><pre-clinical><preclinical><prevent><preventing><programs><prophylactic><resolutions><sterile><toll-like receptor 4><transmission process><vaccine associated immune response><vaccine candidate><vaccine efficacy><vaccine immune response><vaccine immunogenicity><vaccine induced immune response>