VACCINES

One of the greatest triumphs of public health, vaccines have been used for decades to boost immunity and protect against serious diseases. At IDRI, we are developing innovative vaccines against serious and deadly infectious diseases such as tuberculosis, leishmaniasis, and leprosy. Our goal is to produce safe, efficacious and low-cost vaccines for endemic countries. In addition, we are also working to effectively transfer our vaccine technology to developing countries to better serve those in need.

products-vaccinesOur vaccines are made up of to two primary components: an antigen and an adjuvant. Antigens are substances that promote an immune response when introduced into the body. Our antigens are comprised of specific proteins, selected based on their ability to elicit an immune response to the pathogen and later combined as fusion proteins with our novel adjuvants. Adjuvants are substances added to vaccines to help boost antigen effectiveness.

With our large library of adjuvant formulations, we have been able to select the optimal antigen and adjuvant combination for each vaccine in our product pipeline. In addition, we provide adjuvants to others for incorporation into their vaccine candidate products.

Currently, we have a lead candidate vaccine in development for each of our three in-house vaccine programs.

TUBERCULOSIS VACCINE

CHALLENGE

rheainsouthafrica23Mycobacterium tuberculosis, the bacteria that causes tuberculosis, lies dormant in one-third of the world’s population, and activation results in one of the world’s deadliest infectious diseases, killing 1.5 million and causing illness in 9 million last year alone. The currently available TB vaccine, Bacille Calmette-Guérin (BCG), developed 90 years ago, reduces the risk of severe forms of TB in early childhood but is not effective once a person reaches adolescence or in any person with a positive tuberculin skin test. BCG also varies in effectiveness across the globe, particularly in developing countries where the burden is greatest.

SOLUTION

IDRI has developed a tuberculosis vaccine candidate designed to recognize both active TB (when a person has TB disease, is infectious and is suffering from symptoms of the disease, such as fever, coughing and weight loss), and latent TB (when a person is infected with M. tuberculosis but is not symptomatic and is not infectious). The candidate, ID93 + GLA-SE, is composed of a recombinant fusion-protein antigen plus IDRI’s proprietary adjuvant, GLA-SE, and has been previously tested in humans.

Conducted in the U.S., the first phase 1 trial assessed the safety, tolerability and immunogenicity of the vaccine in 60 healthy adult volunteers with no prior exposure to BCG or M. tuberculosis. The second Phase 1 clinical trial was conducted in South Africa in 66 healthy volunteers, who were BCG vaccinated, with or without latent infection with M. tuberculosis.

©Earl Harper

Both studies showed that ID93 + GLA-SE is safe and elicits a multi-functional immune response. The vaccine is intended to boost the immune response elicited by BCG, and could be used both to prevent TB infection and as a post-exposure vaccine. In addition, the vaccine candidate shows efficacy against both drug-resistant and drug-sensitive strains of M. tuberculosis in animal studies and has also demonstrated efficacy in drug-shortening regimens.

In late 2015, IDRI’s vaccine candidate entered into a Phase 2a trial in South Africa to clinically assess the ability to reduce TB recurrence after treatment. Even after successfully completing an anti-TB treatment regimen, patients may succumb to TB again, thereby threatening TB control programs by promoting spread and drug resistance. Prior Phase 1 clinical trials have shown that IDRI’s TB vaccine candidate boosts immune responses that may protect against TB recurrence.

Baldwin SL, Reese VA, Huang PW, Beebe EA, Podell BK, Reed SG, Coler RN. Protection and Long¬-Lived Immunity Induced by the ID93/GLA¬SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate. Clin Vaccine Immunol. 2015 Dec 9;23(2):137¬47. doi: 10.1128/CVI.00458¬15. PubMed PMID: 26656121; PubMed Central PMCID: PMC4744918.

Orr MT, Beebe EA, Hudson TE, Argilla D, Huang PW, Reese VA, Fox CB, Reed SG, Coler RN. Mucosal delivery switches the response to an adjuvanted tuberculosis vaccine from systemic TH1 to tissue-resident TH17 responses without impacting the protective efficacy. Vaccine. 2015 Nov 27;33(48):6570-8. doi: 10.1016/j.vaccine.2015.10.115. PMID:26541135

Orr MT, Windish HP, Beebe EA, Argilla D, Huang PW, Reese VA, Reed SG, Coler RN. Interferon γ and Tumor Necrosis Factor Are Not Essential Parameters of CD4+ T-Cell Responses for Vaccine Control of Tuberculosis. J Infect Dis. 2015 Aug 1;212(3):495-504. doi: 10.1093/infdis/jiv055. PMID: 25637347

Orr MT, Windish HP, Beebe EA, Argilla D, Huang PW, Reese VA, Reed SG, Coler RN. 2015. Interferon gamma and Tumor Necrosis Factor Are Not Essential Parameters of CD4+ T-Cell Responses for Vaccine Control of Tuberculosis. J Infect Dis 212: 495-504

Coler RN, Hudson T, Hughes S, Huang PW, Beebe EA, Orr MT. 2015. Vaccination Produces CD4 T Cells with a Novel CD154-CD40-Dependent Cytolytic Mechanism. J Immunol 195: 3190-7

LEISHMANIASIS VACCINE

CHALLENGE

Leishmaniasis is a parasitic disease that occurs in 88 countries around the world. It has an estimated annual incidence of two million cases and a prevalence of 12 million cases. Visceral leishmaniasis, the most severe form of the disease, affects vital organs and has a high fatality rate if not treated. Cutaneous leishmaniasis, the most common form of the disease, causes serious skin lesions and often leaves its victims permanently disfigured. Drugs to treat leishmaniasis are expensive, toxic or impractical. A safe and efficacious vaccine to control this disease is needed.

SOLUTION

IDRI has developed a vaccine for visceral leishmaniasis. The IDRI vaccine, known as LEISH–F3 + GLA-SE, is a highly purified, recombinant vaccine. It incorporates two fused leishmania parasite proteins and a powerful adjuvant to stimulate an immune response against the parasite.

DSCN1857 - CopyThe vaccine candidate has been evaluated for prophylactic and therapeutic indications in clinical trials in South America, India and Sudan. A Phase 1 clinical trial of the vaccine candidate with 36 adult volunteers was conducted in Washington state. Volunteers were randomly assigned to receive one of three versions of the vaccine, which differed in the amount of adjuvant included. The trial successfully evaluated the safety and immunogenicity of each version.

IDRI is also working on a canine vaccine to combat leishmaniasis. The canine vaccine has been tested in Brazil, where dogs are an important source of human infection. To date, these studies in both humans and canines have shown that the leishmaniasis vaccines are safe, well tolerated, immunogenic and potentially efficacious in the prevention and treatment of diverse forms of leishmaniasis.

Duthie MS, Favila M, Hofmeyer KA, Tutterrow YL, Reed SJ, Laurance JD, Picone A, Guderian J, Bailor HR, Vallur AC, Liang H, Mohamath R, Vergara J, Howard RF, Coler RN, Reed SG. Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis. Vaccine. 2016;34(25):2779-86. doi: 10.1016/j.vaccine.2016.04.067. PubMed PMID: 27142329; PMCID: PMC4889780.

Carter D, Fox CB, Day TA, Guderian JA, Liang H, Rolf T, Vergara J, Sagawa ZK, Ireton G, Orr MT, Desbien A, Duthie MS, Coler RN, Reed SG. A structure-function approach to optimizing TLR4 ligands for human vaccines. Clin Transl Immunology. 2016;5(11):e108. doi: 10.1038/cti.2016.63. PubMed PMID: 27990284; PMCID: PMC5133366.

Schaut RG, Grinnage-Pulley TL, Esch KJ, Toepp AJ, Duthie MS, Howard RF, Reed SG, Petersen CA. Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant. Vaccine. 2016;34(44):5225-34. doi: 10.1016/j.vaccine.2016.09.016. PubMed PMID: 27665354; PMCID: PMC5053902.

Hofmeyer KA, Duthie MS, Laurance JD, Favila MA, Van Hoeven N, Coler RN, Reed SG. Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites. Clin Vaccine Immunol. 2016;23(9):785-94. doi: 10.1128/CVI.00251-16. PubMed PMID: 27466350; PMCID: PMC5014921.

Coler RN, Duthie MS, Hofmeyer KA, Guderian J, Jayashankar L, Vergara J, Rolf T, Misquith A, Laurance JD, Raman VS, Bailor HR, Cauwelaert ND, Reed SJ, Vallur A, Favila M, Orr MT, Ashman J, Ghosh P, Mondal D, Reed SG. From mouse to man: safety, immunogenicity and efficacy of a candidate leishmaniasis vaccine LEISH-F3+GLA-SE. Clin Transl Immunology. 2015;4(4):e35. doi: 10.1038/cti.2015.6. PubMed PMID: 26175894; PMCID: PMC4488838.

LEPROSY VACCINE

CHALLENGE

Kapinga-Kasai Oriental-Pic 2006 - CopyEvery year, an estimated quarter million people worldwide – mostly in Africa, Asia and Latin America –
are diagnosed with leprosy, a cruel disease that leaves its victims maimed, crippled, disfigured and blind, most often with a terrible quality of life. Without new interventions, leprosy – like any infectious disease – could easily spread further, even to the United States. Currently, there is no vaccine to prevent leprosy, a devastating infectious disease that is found in 115 countries.

SOLUTION

IDRI scientists have developed a vaccine – the first designed specifically for leprosy – that can immunize people against leprosy, while also providing treatment to those who have been exposed to the disease but are not yet showing symptoms.

Known as LepVax, the vaccine candidate is designed to control M. leprae (the bacterium that causes leprosy) infection. In addition to its promising level of effectiveness, LepVax is inexpensive to produce, which is particularly important because of the link between the geographic areas where leprosy is most prominent and poverty.

IDRI scientists developed the vaccine through significant efforts in screening and identifying leprosy proteins that trigger an immune response. Our scientists then created and purified a fusion of four leprosy proteins (LEP-F1), which is mixed with IDRI’s proprietary immune-stimulating adjuvant (GLA-SE).

In pre-clinical studies, the LepVax candidate both limits new infections and prevents nerve damage in infected animal models. LepVax can be administered simultaneously with drug therapy to shorten the period of treatment and reduce further transmission.

Based on data generated from animal studies, IDRI’s promising leprosy vaccine candidate is positioned to move into a Phase 1 human clinical trial.

Fonseca AB, Simon MD, Cazzaniga RA, de Moura TR, de Almeida RP, Duthie MS, Reed SG, de Jesus AR. The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy. Infect Dis Poverty. 2017;6(1):5. doi: 10.1186/s40249-016-0229-3. PubMed PMID: 28162092; PMCID: PMC5292790.

Duthie MS, Balagon MF. Combination chemoprophylaxis and immunoprophylaxis in reducing the incidence of leprosy. Risk Manag Healthc Policy. 2016;9:43-53. doi: 10.2147/RMHP.S76058. PubMed PMID: 27175099; PMCID: PMC4854245.

Duthie MS, Coler RN, Laurance JD, Sampaio LH, Oliveira RM, Sousa AL, Stefani MM, Maeda Y, Matsuoka M, Makino M, Reed SG. Protection against Mycobacterium leprae infection by the ID83/GLA-SE and ID93/GLA-SE vaccines developed for tuberculosis. Infect Immun. 2014;82(9):3979-85. doi: 10.1128/IAI.02145-14. PubMed PMID: 25024362; PMCID: PMC4187809.

Oliveira RM, Hungria EM, de Araujo Freitas A, de Sousa AL, Costa MB, Reed SG, Duthie MS, Stefani MM. Synergistic antigen combinations for the development of interferon gamma release assays for paucibacillary leprosy. Eur J Clin Microbiol Infect Dis. 2014;33(8):1415-24. doi: 10.1007/s10096-014-2077-z. PubMed PMID: 24619112.