Papillomavirus, polypeptide and virion aren’t exactly terms that most folks bandy about during conversations at the office water cooler. Thankfully there are those who do — people like Drs. Douglas Lowy and John Schiller, two scientists who discovered a way to generate infection fighting antibodies and made a vaccine against the virus that causes cervical cancer possible.
Cervical cancer is the second most common cause of cancer deaths in women worldwide, killing roughly 230,000 women each year. In the United States, about 10,000 women are diagnosed annually and 40 percent of them die from the disease. It is not typically associated with genetic predisposition, as with many other forms of cancer, but rather linked to human papillomaviruses (HPV), a group of viruses that include more than 100 different strains or types.
More than 30 of these types are sexually transmitted, and HPV infection is the most common STD in the nation. While most HPV infections exhibit no symptoms and clear up without treatment, some infections can persist and lead to cancer. With the help of population studies, scientists discovered that virtually all cases of cervical cancer are caused by infections from one of about 15 strains of HPV, most often HPV16.
Once the scientific community established the connection between HPV and cervical cancer, Lowy and Schiller, who had been studying the molecular biology of HPV, began searching for ways to boost the human body’s immune response to this cancer-causing infection.
Lowy and Schiller discovered that a particular papillomavirus protein, L1, could self-assemble into non-infectious virus-like particles (VLPs) that closely resembled the outer surface of the actual virus and were highly capable of producing an antibody response that inactivated the corresponding virus. Moreover, they found that the L1 of the main HPV16 isolated in labs at the time could not form VLPs because of a mutation. Once they were able to track down non-mutated forms of the virus, they found that the L1 could readily form VLPs that trigger the immune system to produce protective antibodies.
Lowy and Schiller are the first and second inventors on government-owned patents covering these discoveries, which are now licensed to Merck & Co., Inc. and GlaxoSmithKline for commercial development of HPV VLP vaccines. Subsequent human trials of multi-type-VLP vaccines by the two companies demonstrated nearly 100 percent protection against the abnormal growth of cells on the surface of the cervix caused by HPV16 and HPV18, the two types that cause 70% of cervical cancer. In addition, the Merck vaccine prevented most genital warts, which are caused by two other strains of HPV.
Merck’s vaccine, called Gardasil, earned FDA approval in 2006 for treatment of females ranging from ages nine to 26. GlaxoSmithKline applied for FDA approval in 2007. These vaccines are expected to decrease the risk of cervical pre-cancer or cancer by at least 70 percent, thereby substantially affecting women’s health.
While the introduction of Pap tests to detect cancers at an early stage has prevented an epidemic of cervical cancer in the United States and other wealthy countries, effective screening and treatment is not widely available throughout most of the world. In fact, 80% of cervical cancer cases occur in developing countries. At the heart of Lowy and Schiller’s efforts is their steadfast commitment to promoting public health on a global scale. In addition to their service to the World Health Organization, they are helping manufacturers in India to produce the current generation vaccine and to bring to clinical trials two distinct second-generation prophylactic HPV vaccines that are potentially cheaper to produce and deliver.
Lowy and Schiller’s 20-year partnership has been a boon to the nation’s health and for the advancement of scientific discovery.