Neglected Tropical Diseases
AAHI’s immune enhancing platform technologies enable cost-effective and temperature stable vaccines that can be delivered to rural, remote, and low-resource parts of Asia, Africa, and Latin America that are most burdened by neglected tropical diseases (NTDs).
NTDs are debilitating, chronic, and sometimes fatal diseases found primarily in impoverished areas. Caused by a variety of pathogens including viruses, bacteria, parasites, fungi, and toxins, NTDs have devasting impact, especially in remote and rural communities, where access to vaccines is limited by cost and lack of infrastructure for temperature-controlled storage and delivery. AAHI reduces NTD vaccine costs through pragmatically creative product development to make efficient use of limited raw materials and to streamline manufacturing processes, enabling production of more vaccine doses with less raw material and reduced manufacturing costs. All three of AAHI’s platforms – adjuvant formulations, self-amplifying RNA, and delivery vehicles – are designed to be stable for months at ambient (even tropical) temperatures to support ‘last-mile’ delivery to the people who are most burdened by NTDs.
AAHI collaborates with partners around the world to develop affordable, temperature-stable vaccines and diagnostics to fight NTDs:
AAHI has developed both a diagnostic test for visceral leishmaniasis (VL) that spares patients painful and potentially dangerous spleen or bone marrow biopsies and an innovative vaccine that has demonstrated safety and immunogenicity in Phase 1 clinical trials.
The bite of the female phlebotomine sandfly, no bigger than the tip of a crayon, can transmit the parasites that cause visceral, cutaneous, and mucosal leishmaniasis (VL, CL, and ML, respectively). VL is 95% fatal if untreated and causes fever, weight loss, and anemia. CL and ML are less severe but can cause serious disabilities. In 2017, the World Health Organization estimated that leishmaniasis caused the loss of over half a million years of health for people primarily living in Brazil, Ethiopia, India, Sudan, Kenya, and Somalia. An estimated 50,000 to 90,000 new cases of VL occur worldwide annually. While insecticide sprays and nets can deter the sandflies, there is no vaccine yet to prevent any of the leishmanial diseases.
AAHI scientists were instrumental in development of diagnostic proteins used in simple and rapid blood tests for VL that deliver easy-to-read results in just ten minutes. These proteins enable diagnostic tests that do not require the previously standard painful needle biopsies of the spleen or bone marrow. These diagnostic tests are widely distributed in areas most burdened by VL, including Brazil and India.
AAHI has also created a VL vaccine, combining AAHI’s innovative recombinant protein, LEISH-F3, with AAHI’s immune-stimulating adjuvant formulation GLA-SE. The vaccine demonstrated safety and immunogenicity in Phase 1 clinical trials (NCT01484548 & NCT01751048).
LEISH-F3 was later formulated with AAHI’s SLA-SE adjuvant formulation and tested in comparison to GLA-SE in a Phase 1 clinical trial sponsored by the Bill and Melinda Gates Foundation (NCT02071758). Both vaccine formulations were shown to be safe and to induce the desired immune response.
AAHI has long supported development of a Chagas vaccine, licensing recombinant proteins and its GLA-SE adjuvant formulation to support research and development and upcoming clinical trials.
Chagas disease is caused by the feces of the triatomine bug found in the tropics of Latin America and Mexico, which contains a life-threatening parasite, Trypanosoma cruzi. Outbreaks of Chagas disease are common in areas without adequate sanitation, given that infection can be caused by simple contact or accidental consumption of contaminated food or water. People exposed to T. cruzi may suffer chronic heart, digestive, and neurological conditions. The disease is curable if treatment is administered soon after infection, yet in 2017, ten thousand people died of Chagas disease. Somewhere between six and seven million people are estimated to be currently infected, and an additional seventy-five million people are at risk of being infected.
The WHO’s goal is to eliminate transmission of Chagas disease in fifteen of the forty-one currently affected countries by 2030. In alignment with this goal, AAHI is collaborating to support development of a Chagas vaccine candidate that combines a recombinant T. cruzi protein, Tc24-C4, with AAHI’s GLA-SE adjuvant formulation. The vaccine candidate is expected to enter the clinic in 2023.
AAHI’s adjuvant formulations are supporting development of three different schistosomiasis vaccine candidates, currently in early phase clinical testing in Uganda, Brazil, Madagascar, Burkina Faso, and the Netherlands.
Schistosomiasis is caused by infection with parasitic trematode worms. Certain species of fresh-water snails, native to Africa and Brazil, carry the worms, which are shed in larval form. Once released by the snails, the larval worms, or bloodflukes, actively seek hosts. They use their forked tails to penetrate the skin of people who are bathing, swimming, or washing clothes, entering their bloodstreams, and nesting in various organs, particularly the intestines, bladder, and genitals. In 2019, almost two and half million people were treated with mass chemotherapy to kill such infestations. Since 2020, 66% of countries where schistosomiasis is endemic require preventative chemotherapy to combat schistosomiasis.
AAHI is collaborating with partners around the world to develop schistosomiasis vaccines that will deter the worms from considering humans a viable host, and thus may avoid the need for potentially harmful preventive chemotherapy. Three such schistosomiasis vaccine candidates are being clinically evaluated with AAHI’s GLA adjuvant formulations that enhance the body’s immune response to the vaccine.
Baylor College of Medicine is conducting a Phase 1 /2 clinical trial in Uganda evaluating their SmTSP-2 protein on alum combined with AAHI’s GLA-AF adjuvant formulation to protect against intestinal schistosomiasis. The vaccine candidate was proven safe and well- tolerated in a Phase 1 clinical trial conducted in Minas Gerais, Brazil (NCT02337855 & NCT03910972).
Another vaccine candidate, developed by researchers in Brazil, combines a fatty acid binding protein, Sm14, with AAHI’s GLA-SE adjuvant formulation. The Phase 1 clinical trial, sponsored by Oswaldo Cruz Foundation (FioCruz) and conducted in Rio do Janeiro, demonstrated that the vaccine candidate was well- tolerated and induced a favorable immune response (NCT01154049). The researchers recently completed Phase 2 clinical trials in Senegal to protect school children between the ages of 8 and 11 (NCT03799510) and are currently recruiting for a clinical trial in Senegalese adults exploring different vaccine dosing regimens (NCT05658614).
A third vaccine candidate called SchistoShield®, combining a recombinant protein Sm-p80, or calpain, with AAHI’s GLA-SE adjuvant formulation, entered clinical testing in 2022 in Seattle, supported by the National Institute of Allergy and Infectious Diseases (NIAID) (NCT05292391). Researchers have plans to commence a Phase 1b clinical trial in Madagascar and Burkina Faso, with a human challenge model study planned in the Netherlands.
AAHI has developed a leprosy vaccine, “LepVax,” that combines an innovative fusion protein (LEP-F1) with AAHI’s GLA-SE adjuvant formulation. LepVax has proven to be safe and immunogenic in a phase 1 clinical trial. A Phase 1/2 clinical trial is anticipated to begin soon in Brazil.
Leprosy, or Hansen’s Disease, is caused by a slow-growing bacteria and, if untreated, results in physical deformity such as skin lesions, loss of eyebrows and eyelashes, and erosion of fingers and toes, with accompanying nerve damage. The bacteria that causes these devastating symptoms, Mycobacterium leprae, is found in many locations including India, Brazil, and Indonesia. It is primarily transmitted by droplets from the nose and mouth during prolonged close contact with untreated leprosy patients. Current leprosy treatments entail lengthy multidrug therapy that requires continual monitoring and cannot remedy existing physical or nerve damage. In 2019 alone, there were over two hundred thousand new leprosy cases, almost fifteen thousand of whom were children.
AAHI’s LepVax vaccine candidate is designed to provide protection to families or other close contacts of leprosy patients in leprosy-endemic regions. It is simple and inexpensive to manufacture at large scale and has been shown to be safe and well tolerated in a Phase 1 clinical trial conducted in collaboration with the American Leprosy Mission (NCT03302897). LepVax is anticipated to be evaluated in both healthy adults and leprosy patients in Brazil in a Phase 1 / 2 clinical trial sponsored by FioCruz (NCT03947437).
AAHI is supporting development of a hookworm vaccine candidate, currently in Phase 2 clinical testing, that uses AAHI’s GLA-AF adjuvant formulation.
The microscopic hookworm thrives in the soil of warm, moist climates, including many areas that are affected by extreme poverty and poor sanitation. Once widespread in southeastern United States, hookworm is now most prevalent in regions of sub-Saharan Africa, South Asia, and South America. Larvae of the worms are spread from contaminated stool to soil, where they hatch. Worms then infect people who walk barefoot on contaminated soil, infesting their intestines and causing weight loss, fatigue, and anemia. Today, an estimated six to seven and a half million people are infected with hookworm in areas of the world that cannot afford functional sewer systems and outhouses.
AAHI is collaborating with Baylor College of Medicine and partners in Brazil to support hookworm vaccine candidates that deter larvae from latching on and penetrating human skin. The vaccine candidates combine a recombinant hookworm protein, Na-GST-1 or Na-APR-1, with AAHI’s GLA-AF adjuvant formulation, and were safe and well tolerated in Phase 1 clinical trials in Brazil and the United States (NCT01261130, NCT01717950, NCT02126462, NCT02476773, and NCT01385189). The clinical trial results led to support from National Institute of Allergy and Infectious Disease (NIAID) and George Washington University to conduct an ongoing Phase 2 clinical trial in the U.S. (NCT03172975).
Bovine TB in humans
AAHI scientists supported development of a bovine TB diagnostic for detection of the bacteria in cattle to prevent transmission from contaminated milk products to humans.
Bovine tuberculosis is a type of TB that primarily affects animals, such as cattle and deer, but can be transmitted to humans through consumption of raw milk products containing the bacteria. People who work with cattle and on ranches are particularly susceptible. In areas where milk is typically not pasteurized to eliminate bacteria, one hundred and forty thousand people each year are infected by, and more than twelve thousand people lose their lives to, this zoonotic form of tuberculosis. While the disease is curable with a cocktail of antibiotics administered over 6 months to a year, if not treated quickly, it can cause permanent disability and/or death. It is difficult to provide access to effective diagnostics and treatments for bovine TB in rural areas with sprawling farmlands, where infection is most likely to occur.
AAHI collaborated with Chembio Diagnostic Systems to create an innovative highly sensitive recombinant protein diagnostic for bovine TB in animals. The test identifies infected animals, and thus makes it possible to eliminate transmission to humans by decontaminating or avoiding milk products from those animals. Development of this important diagnostic test was supported by the National Animal Disease Center of the US Department of Agriculture.
AAHI is developing a cryptosporidium vaccine candidate on its temperature-stable self-amplifying RNA platform.
Cryptosporidium, or “crypto,” are microscopic parasites found in all areas of the world but posing a particularly high risk to people living in communities with poor water treatment and inadequate food sanitation. Crypto resides in human intestines and causes watery diarrhea, nausea, stomach pain, and dehydration. While crypto symptoms are quite inconvenient and uncomfortable, most otherwise healthy adults will recover by drinking plenty of fluids to flush the parasites out of the body. Infection with cryptosporidium is a far more serious, even life-threatening, matter for people with weak immune systems, pre-existing health conditions, malnutrition, and/or dehydration.
AAHI is collaborating with the University of Virginia to develop a self-amplifying RNA vaccine against cryptosporidium. AAHI’s RNA platform enables development of a vaccine that addresses the most prominent barriers to global protection against cryptosporidium. AAHI’s RNA vaccines can be stored at ambient temperatures, so they can be transported to parts of the world without deep cold chain infrastructure, such as the remote and rural areas of the world without safe drinking water where cryptosporidium is a threat. AAHI is developing intranasal and dry powder formulations of its RNA vaccines that do not require trained medical personnel for administration, so they can more effectively be made available in impoverished or remote areas without well-developed health infrastructure. And finally, AAHI’s RNA vaccines have demonstrated safety and efficacy in immunocompromised patients, those for whom cryptosporidium infection poses the gravest risk.