Gadget Blog

A biotech company is pursuing an approach that could redefne infectious medicine.

For some infectious diseases, traditional  vaccines just don’t cut it. Microbes that  hide inside human cells and cause chronic  illness aren’t stymied by the antibody response  generated by the kinds of vaccines available at  the doctor’s ofce. T-cell vaccines, which acti- vate a diferent type of immune response, could  in theory ofer a better way to prevent or control such infections, but so far nobody has been  successful at bringing T-cell vaccines from the lab bench to the clinic.

A colored scanning electron micrograph depicts a t cell.

Now Genocea, a biotech company in Cam- bridge, Massachusetts, thinks it can do it. It will  test the claim this fall with its frst clinical trial,  on an experimental herpes vaccine.

All existing vaccines rouse the body into  creating antibodies that attach to the sur- face of infecting microbes and fag them for  destruction. But pathogens that live inside our  cells, such as the viruses, bacteria, and other microbes that cause AIDS,  malaria, herpes, and chla- mydia, can evade this sur- veillance. “In order to deal  with those types of pathogens, oftentimes we  have to stimulate what we call cellular immunity,” says Genocea cofounder Darren Higgins, a  Harvard biologist. “Unlike antibody immunity,  which recognizes pathogens directly, cellular  immunity has to recognize the infected cell and  get rid of your own infected cells.”

It’s challenging to activate cellular immunity and the family of infection-fghting cells,  known as T cells, that drive it. The trial-and-error method used to develop antibody-based  vaccines has not worked for T-cell vaccines.

Despite years of academic and industry work,  and even clinical trials, there are no T-cell vaccines for infectious disease on the market. “We  don’t know all of the rules yet—if it’s possible  to make a T-cell vaccine, [or] how efective it  would be,” says Robert Brunham of the University of British Columbia, who is developing  a T-cell vaccine against chlamydia.

Indeed, our understanding of how T cells  control infection is still developing. The challenge is to identify the pathogen protein that  will grab a T cell’s attention and signal that a  human cell harbors an infectious agent. “If you can fgure out what those protein pieces are,  then you can use those proteins as a vaccine to  sort of educate your immune system on what  to respond to,” says Higgins.

The challenge gets tougher with pathogens whose genomes encode more proteins. 
There are 80 or so proteins in the herpes simplex 2 genome, about 1,000 in chlamydia, and  5,000 or so in malaria. Genocea has a high- throughput screening method in which it col- lects as many of a pathogen’s proteins as can  reasonably be produced in a lab and then monitors how human immune cells respond to each.

Although Genocea’s herpes vaccine is still  unproven, the work is moving faster than typical vaccine research, which can take 10 years  to go from discovery to proof of concept and  20 years to reach the market.