Introduction

Filariae are tissue-invasive parasitic nematodes that cause human diseases such as lymphatic filariasis, river blindness and African eyeworm; affecting over 200 million people worldwide. In addition to human disease, filarial parasites infect dogs and cats causing heartworm infections. Currently, no vaccine exists to prevent either human or animal filarial infections. Treatments have limited macrofilaricidal activity, and interruptions in medication risks repopulation by microfilariae. A vaccine for filariasis could significantly reduce the morbidity in both humans and companion animals. Investigators at the Uniformed Services University of the Health Sciences (USU), United States Public Health Service (PHS) and the National Institute of Allergy and Infectious Diseases (NIAID) have identified vaccine candidates to overcome potential allergic reactions, a principal obstacle in the development of vaccines against filaria. These antigens have been demonstrated as critical to filarial survival and replication.

Applications and Advantages

• Novel animal model of filariasis for use in small/large molecule screening and clinical trial studies.
• Vaccine development using novel antigens that overcome host allergic reactions and which have been demonstrated, by the investigators, to be pivotal to worm survival and replication.

Description of the Invention

Researchers have disclosed and refined immunogenic compositions and vaccines designed to prevent or treat filarial diseases caused by parasitic nematodes such as Brugia malayi, Wuchereria bancrofti, Onchocerca volvulus, Loa loa, and Dirofilaria immitis (heartworm). The core of the invention is an immunogenic composition comprising at least one or two isolated polypeptides—or immunogenic fragments thereof—that are specifically expressed on the luminal surface of the intestine of filarial worms. These polypeptides are characterized by having at least a two-fold higher expression level in the worm’s intestine compared to its reproductive tract or body wall, contain at least one transmembrane domain, and are non-mitochondrial proteins. By targeting intestinal antigens that are “hidden” during natural infection but accessible upon vaccination, this approach aims to elicit protective immune responses with reduced risk of allergic reactions seen with other worm surface antigens. The invention also covers methods for preventing or treating filarial infections by administering these compositions, which may include adjuvants, to subjects at risk or already infected, including humans and animals like dogs. The disclosed polypeptides have been identified through proteomic analysis and show potential as effective vaccine candidates against major filarial pathogens causing lymphatic filariasis, river blindness, loiasis, and heartworm disease.

Innovation Status

Top vaccine candidates have been selected based on in vitro worm viability/survival, metabolic activity, anatomic structure, and microfilaria production. Expression systems are being developed for selected candidate proteins, to be followed by screening for IgE antibodies against these recombinant proteins in the plasma of filaria‐infected humans. Testing in animal model of filariasis, and B. malayi challenge for companion animal treatment of heartworm. Pre-clinical development and testing of specific human vaccine candidates are in progress.

Intellectual Property Status

A patent is in force in the United States: 10,441,642