To date, for all their successes, vaccines only harness part of the immune system: antibody-producing B cells.

"Pretty much every vaccine on the market today is believed to function by eliciting antibodies," Darren Higgins, associate professor of microbiology and molecular genetics at Harvard Medical School, told BioWorld Today.

But New York-based Genocea, Inc., which was co-founded in 2006 by Higgins, along with Sirtris co-founder David Sinclair and venture capitalists from Lux Capital Management and Polaris Venture Partners, aims to change all that. The company says it has a way of screening, in a matter of a few weeks, every protein in a pathogen for its potential to elicit an immune response. The technology could be used to identify optimal antigens for both a B- and T-cell response, but Genocea plans to focus on killer and helper T cells.

"With prevailing methods, it might take years" to discover an antigen that is vaccine material, Higgins said. "We can effectively cut that down to a couple of weeks."

Vaccines that stimulate T cells generally are acknowledged to have enormous promise, but it hasn't been smooth sailing on the way to their clinical use. The most advanced therapeutic vaccine in development, Provenge from Seattle-based Dendreon Corp., is a therapeutic cancer vaccine, not a preventive infectious disease vaccine. But it has seen its share of ups and downs.

The vaccine demonstrated a survival trend, but missed its primary endpoint of time to disease progression in two Phase III studies. Nevertheless, Dendreon submitted a biologics license application, which was deemed approvable in May, though final approval ultimately hinges on positive data from a confirmatory Phase III trial (See BioWorld Today, May 10, 2007, and Nov. 5, 2007.)

While toxicity profiles of vaccines aimed at stimulating T cells generally have been favorable, efficacy has been less than stellar. At least part of the problem is that current technologies to identify antigens are not comprehensive, and so do not necessarily manage to find the antigens that will give the strongest overall immune response.

While Genocea remains mum on the details of its technology, co-founder Robert Paull, who also is the company's interim CEO, as well as managing partner of Lux Capital, told BioWorld Today that it "removes the guesswork from antigen discovery."

Genocea's technology, Higgins said, can "produce, express and target every single protein from a pathogen to an appropriate antigen-presenting cell" at a speed that makes it realistic to sort through them all.

They hope that using that method will enable the company to truly pick the best antigen for the job when designing vaccines - antigens that will stimulate a sufficiently strong response in both killer and helper T cells to make T-cell based vaccines successful. Such targets can then be incorporated into existing antigen delivery systems to make multivalent vaccines.

The company announced today that it has signed a deal with Harvard Medical School licensing 14 antigens to the bacterium Chlamydia trachomatis that were discovered in Higgins' lab.

Higgins and Paull said the technology's success at identifying Chlamydia antigens illustrates the main strengths of Genocea's technology, which, thanks to its speed, is well-suited to deal with intracellular pathogens with large genomes. Paull said that the company's name refers to its ability to "screen an ocean of genes."

The ability to deal with intracellular pathogens comes from the company's focus on T cells. "A lot of pathogens that don't have vaccines for them right now are intracellular pathogens," Paull explained, because growing intracellularly provides a pathogen with the perfect hideout from antibodies.

But T cells can see and respond to such pathogens, whose proteins end up on the surfaces of infected cells, presented by major histocompatibility complex or MHC proteins whose job it is to let T cells check up on what's going on inside cells.

"As [infected cells] are growing, they are making pathogen proteins," Higgins said. And those proteins, once they are presented on the cell surface, signal to T cells that "this cell is not quite self."

The need for developing vaccines against large intracellular pathogens is certainly there, and possible targets include such scourges as malaria - which Genocea is doing "a little work" on, Paull said - and tuberculosis. Chlamydia itself is the leading bacterial sexually transmitted disease in the U.S., with an estimated three million infections annually.

While acute Chlamydia infections, by themselves, usually are harmless, untreated Chlamydia can cause much more serious secondary problems, including pelvic inflammatory disease and infertility. Paull compared a possible Chlamydia vaccine to Whitehouse Station, N.J.-based Merck & Co. Inc.'s Gardasil, which prevents infection with human papillomavirus but really is aimed at preventing the viruses' more serious possible consequence of cervical cancer.