History

Genocea was founded in 2006 based on technology from University of California at Berkeley and Harvard Medical School.

Background

Infectious diseases are the third leading cause of death each year in the United States and the world's leading killer of children and young adults, accounting for more than 14 million deaths annually. In addition, numerous infectious diseases, while not major killers, cause chronic disability for millions and lead to tens of billions of dollars in excess healthcare costs. Many infectious diseases, such as malaria and tuberculosis (two of the top five global killers) as well as chlamydia (the most frequently reported bacterial sexually transmitted disease in the United States), are caused by pathogens that are capable of growing within human cells (intracellular pathogens). Despite the devastating health and economic impact of these diseases, and in spite of significant efforts to develop vaccines, no effective vaccines currently exist against these or a multitude of other intracellular pathogens.

Because these pathogens grow sequestered within host cells, the humoral (antibody-mediated) immune response is often ineffective in providing protective immunity. Instead, for many intracellular pathogens, protective immunity requires the generation of a robust cellular immune response mediated by T lymphocytes (also called T cells). T cells can be generally classified as CD8+ cytotoxic T lymphocytes (CTL) or CD4+ Helper T cells, that respectively, recognize and eliminate pathogen-infected host cells or produce compounds such as cytokines that stimulate other immune cells to help fight infection.

To activate T cell responses during a natural infection, invading pathogens are initially engulfed by specialized antigen-presenting cells (APCs). Immunogenic pathogen-derived proteins or antigens are subsequently processed into smaller peptides and placed on the surface of the APC for recognition by CD8+ or CD4+ T cells. Upon recognition, T cells are activated to help eliminate the infection. Activated T cells also divide and become long-lived memory T cells that can rapidly respond to infection should the host contact the infectious agent again, thus providing long-term protective immunity.

While most traditional vaccine strategies involve the use of entire organisms (either live-attenuated or killed) during immunization; it is advantageous to deliver only the portion of the organism that is responsible for stimulating a protective immune response (i.e. the antigens themselves). Such subunit or component vaccine strategies offer advantages in safety, manufacturing, and potentially efficacy assuming the most appropriate antigens can be identified. While several advances have been made in antigen delivery methods, relatively few advances have been made in developing strategies to rapidly identify, out of the thousands of possible candidates for each pathogen, protective T cell antigens that can be incorporated into vaccine formulations. Therefore, the development of strategies to identify pathogen-specific CD8+ and CD4+ T cell antigens is of fundamental importance in the rational design of vaccines against numerous pathogens.

Many vaccine programs, especially those targeting intracellular pathogens, have been ineffective because there is currently no way to efficiently screen all possible antigens from a pathogen that may encode hundreds or thousands of proteins. As an alternative; numerous in silico methods have been developed to identify via prediction algorithms, which bacterial or viral proteins will be antigenic. To date, such efforts have not been successful and have amounted to little more than a different approach to trial and error.