September 8, 2014
Amidst the clamor and excitement of the ongoing hepatitis C (HCV) treatment renaissance, one word is rarely uttered: vaccine.
In fact, at ICAAC 2014 in Washington, D.C., a major symposium devoted to updating infectious disease specialists on the current state of HCV immunopathogenesis and treatment nearly avoided mentioning the subject at all. Vaccines did not enter into the conversation until the last 10 minutes of the 120-minute-long session.
During a question-and-answer period following a series of presentations exploring new HCV treatments, recent research on liver transplantation and innate immune response to HCV, the conversation briefly turned to HCV prevention. Symposium co-convener Emily Blumberg, M.D., a professor of medicine at the University of Pennsylvania's Perelman School of Medicine, suddenly turned to her colleagues and asked, "Speaking of prevention: Why is there no vaccine for this yet? What's the status of vaccination for hep C?"
"It's been difficult, partially because the virus is incredibly mutable. If you [take] HCV and you compare it to the heterogeneity of HIV, all the HIV variants fit into one genotype of HCV in terms of RNA sequence heterogeneity, which is quite remarkable considering how variable HIV is. So it's been hard to develop that.
"And I guess, if you think about it, in the natural experiment -- someone gets infected with HCV, spontaneously clears hep C -- they do have a greater likelihood of clearing if they're reinfected, but the fact that they still can be reinfected means that natural immunity doesn't provide protection. It's very hard to improve on natural immunity, so I think it's gonna be a long time.
"There are some vaccine candidates. It's gonna be a struggle, and I think now there's less enthusiasm for developing a vaccine because the therapy is so good."
Feld is not alone in his skepticism. Writing in Expert Review of Gastroenterology and Hepatology last year, Alexander Ploss, Ph.D., and Chao Shi, Ph.D., of Rockefeller University temper optimism -- "If we are experiencing a harvest season for [direct-acting antivirals], the coming one is for HCV vaccines" -- with realism: "[F]ew vaccination approaches are being evaluated in clinical trials," they write, "making it unlikely that a pan-genotypic vaccine will become accessible within the next half decade."
In addition to the tremendous genetic diversity of HCV noted by Feld at ICAAC, Ploss and Shi point to our less-than-full understanding of HCV immunology as a major obstacle to vaccine research. They also mention a challenge that society has imposed on itself: the recent push in many countries to severely restrict research involving chimpanzees and other great apes.
"Because of a narrow species tropism of HCV, chimpanzees are the only in vivo experimental model with competent immune system available for HCV vaccine research, but those studies are limited due to ethical concerns, restricted availability and prohibitively high costs," Ploss and Shi write. "As a result, much of our knowledge in HCV immunology relies on the studies of a very small number of animals. ... The lack of accessible animal models is also a hurdle for testing the efficacy of vaccine candidates."
As has been true in so many aspects of the response to two similar-yet-different viral pandemics -- HIV and HCV -- the current state of vaccine development echoes between them. In both cases, research toward a vaccine is ongoing, and there may one day be a successful preventive vaccine for one or both viruses. But in both cases, progress has been slow and stilted, no clear pathway to an effective vaccine exists, and attention toward vaccine research in recent years has been deeply overshadowed by other avenues of prevention, treatment and cure research that have proven far more successful.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
Follow Myles on Twitter: @MylesatTheBody.
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