Genocea Biosciences Fast Facts
- Vaccine market grew to ~$42 Billion in 2012
- Multiple targets remain (Chlamydia, Hepatitis, HIV, HSV-2, Malaria, TB)
Herpes (HSV-2) Therapeutic Vaccine Candidate
- Estimated size of HSV-2 patient population: 500 million people worldwide
- Phase 1/2a Trial of 150 patients with HSV-2
- Endpoints: Viral Shedding, Immunogenicity, Safety
- Secondary endpoint: Clinical Symptoms
Genocea’s Active Pipeline
- Herpes Therapeutic Vaccine: Phase 1/2a Trial (ongoing)
- Pneumonia Vaccine: Phase 1 Trial (planned)
- Chlamydia Vaccine: Phase 1 Trial (planned)
- Herpes Vaccine: Preclinical
By Poncie Rutsch
Master of Science Candidate
Boston University Science Journalism
The scope of the genital herpes problem is daunting. The disease—technically known as HSV-2—affects one in every six people between the ages of 14 and 49 in the United States. Worldwide infection estimates reach 500 million. While not life-threatening for adults, those infected often take daily drug regimens to manage outbreaks of lesions, which can be both physically and psychologically painful.
“Individuals with herpes can have great difficulty developing and maintaining close relationships,” said Chip Clark, CEO of Genocea Biosciences, which is advancing a novel T cell therapeutic vaccine for herpes in clinical trials. “This is something many take for granted, but for those with the disease the psychological toll of not being able to live life to its fullest is extremely hard.”
Unfortunately, there have been few new pharmacological answers for preventing herpes and many similar diseases that can take root outside of the bloodstream and evade traditional vaccines. And for those already infected, high hopes for therapeutic vaccines that can decrease or eliminate such pathogens have gone unfulfilled.
Quest for First Vaccine Targeting T Cell Responses
To take on herpes, HIV, Chlamydia and similar diseases where they thrive, the body may have to destroy its own infected cells—which it can do quite effectively given the proper response from the body’s T cells, powerful immune system cells that can cross cellular boundaries.
However, harnessing this aspect of the body’s natural defense system has stymied drug developers. Despite years of academic and industry work, and even clinical trials, there are no vaccines on the market designed to induce T cell responses against infectious diseases.
The problem has been the intertwined combination of human genetics and the sheer volume of potential pathogen-specific T cell targets.
Unlike vaccines designed to induce antibody responses, T cell activating targets (antigens) may work in some populations but not in others. Identifying the perfect antigens by testing many thousands of pathogen candidates across multiple human T cell variations is the proverbial needle in the haystack problem.
To overcome this challenge, Darren Higgins, Harvard Medical School Professor of Microbiology and Immunobiology and co-founder of Genocea, developed a process to rapidly screen and test potential T cell antigens. “At Genocea, we can mimic the human body’s immune response in the lab and quickly narrow the vaccine candidate pool,” said Higgins.
Genocea’s system, called ATLAS (Antigen Lead Acquisition System), allows every pathogen protein to be interrogated against the T cell immune system of hundreds of people exposed to a pathogen. Thus, ATLAS can rapidly identify the target antigens associated with protective responses. By the time the testing is completed, ATLAS has narrowed potentially thousands of proteins down to a handful of vaccine candidates.
Compared to industry standards, ATLAS works incredibly fast and has benefited Genocea’s vaccine development programs. The company’s herpes program, for example, began in 2007 and is nearing the completion of its first phase 1/2a trial. Typical vaccine research can take 10 years to advance from discovery to initial proof-of-concept and even longer to reach the market. Said Higgins, “Now you can screen very rapidly to determine what is going to be the optimal vaccine components that allow you to get into clinical trials at a rapid rate.”
Genocea’s Herpes Therapeutic Vaccine
People infected with herpes show a range of T cell responses to the virus. Using ATLAS, Genocea compared exposed-but-not-afflicted patients to patients who were very clearly afflicted, and determined which viral proteins provoked a protective T cell immune response.
In testing in guinea pigs, the closest herpes model to humans, vaccine candidates demonstrated a significant decrease in the number of visible outbreaks and subclinical viral shedding, which is how the virus spreads to sexual partners in humans.
Buoyed by the success of its preclinical testing, the company then launched its first human clinical trial last year, a phase 1/2a trial of 150 patients with clinically active herpes. To take part in the trial, patients needed to have four or more documented outbreaks within 12 months leading up to receiving the therapeutic vaccine candidate.
There is great anticipation by many as the trial nears completion. Patients and industry observers will be particularly focused on viral shedding, i.e. the therapeutic vaccine’s ability to decrease the viral load in infected patients. If successful across all of its endpoints, which also include safety and immunogenicity, Genocea could bring the therapeutic vaccine candidate into a phase 3 trial by 2016. Genocea would also look to advance a prophylactic vaccine.
“An approved vaccine would have the potential to impact patients on multiple levels,” says Higgins. “For many people, the benefits would be life changing.”