A Vaccine for Lymphatic Filariasis, LFGuard™

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.