Next Generation Pulmonary Malarial Vaccine

Summary Scientists encounter difficult obstacles in attempting to develop vaccines against malaria. For example, malaria parasites of the same species but isolated from different geographic locations may be genetically and immunologically distinct, so vaccines that protect against one geographic isolate may not protect against another. Additionally, malaria parasites have complex life cycles with multiple distinct developmental stages creating potentially thousand of different antigens that could serve as targets of an immune response. Finally, because protection appears to require both antibody-mediated and cell-mediated immune responses, identifying delivery systems and formulations that stimulate all the aspects of immune reactivity represents enormous technical challenges. Professor David Edwards and colleagues at Harvard University have overcome these limitations by developing a nanoparticle vaccine system that does not require multiple doses, provides sustained immunity, and induces more complete (humoral as well as cellular) immunity.

A next-generation pulmonary malarial vaccine. The formulation includes nanoparticles in the aerodynamic range of 1-5 microns that invade deep into the lung and provide sustained release of AMA-1 and MSP-1 malarial antigens. AMA-1 and MSP-1 been extensively studied for use in malaria vaccines and are known to elicit immune response in humans. The aggregate particles degrade in the body, MSP-1 and AMA-1 proteins are released into the blood, and phagocytosed by APCs thereby initiating the cellular immune response.

Applications A major difficulty in developing peptide based vaccines against malaria is the polymorphism inherent in the parasites presentation of surface antigens. The malarial vaccine described herein is composed of multiple antigens from different stages in the life-cycle-this is thought to hold greater promise than single vaccines and provides a platform for next generation parasitic vaccines. Another advantage is that pulmonary administration of the vaccine is done without the need for medical intervention; thus the pain associated with injection therapy is avoided. Also, the lungs provide a large mucosal surface for drug absorption and are lined with phagocytic cells of the immune system, which provide a means for introducing antigens to a large number of immune cells immediately following administration. There also is no first-pass liver side-effect of absorbed drugs nor enzymatic and pH mediated degradation of the bioactive agent frequently encountered with oral

There is a need for cheap and easy to administer vaccines for diseases of third world countries. In the case of malaria, there are 1.1 million deaths annually with an estimated 300 and 500 million new cases each year. The drugs currently available, such as chloroquine and malarone, are too expensive, hard to achieve patient compliance with, and many strains develop drug resistance to them.

Publications: Tsapis, N et al. Trojan particles: Large porous carriers of nanoparticles for drug delivery. Proceedings of the National Academy of Engineering, 99, 12001-12005 For Further Information Please Contact the Director of Business Development Laura Brass Email: Telephone: (617) 495-3067

Inventor(s): Edwards, David A

Type of Offer: Licensing

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