The prestigious Lasker-DeBakey Clinical Medical Research Award for 2017 was awarded to two scientists who did groundbreaking work conceptualizing and developing a vaccine for human papillomavirus, the pathogen responsible for almost all cases of cervical cancer and for many other cancers as well. Prize recipients Douglas R. Lowy, MD, and John T. Schiller, PhD, of the National Cancer Institute (U.S. National Institutes of Health) devised a unique solution to a vaccine for an oncogenic (cancer-causing) virus.
Lowy and Schiller’s research rested upon some key earlier discoveries. Harald zur Hausen (2008 Nobel Prize in Physiology or Medicine) in 1983 had made the connection between HPV infection and cervical cancer. In the 1990s Scottish-Australian immunologist Ian Frazer had assembled a virus-like particle (VLP) somewhat resembling the outer shell of HPV16, but not including the genome inside, from two proteins, L1 and L2, that make up the shell of the virus. His particle, however, was imperfectly assembled and smaller than the actual virus. It provided an idea for a vaccine, but it would have required much additional work.
Lowy and Schiller appreciated Frazer’s research because it did not risk making a vaccine from oncogenic parts of HPV. They decided to try Frazer’s method but with a related virus, bovine papillomavirus. Lowy had previously developed a method to detect and quantify BPV infection in cells grown in the lab – an advance that had not yet been made for HPVs and yet one that would greatly aid vaccine research.
Working with insect cells as “factories” to produce L1, they were able to assemble BVP VLPS out of L1 proteins. These VLPs were the same size and shape as the complete virus. To test whether the VLPs could mimic the virus well induce to induce immunity, Lowy and Schiller exposed rabbits to cells containing the VLPs. Then they were able to use blood serum from the rabbits to inhibit BPV infection of cells in the laboratory. But this was a vaccine model for BPV, not HPV.
When Lowy and Schiller tried their method of VLP construction with the standard reference strain of HPV16, it didn’t work. The VLPs did not match the outward appearance of the virus. The scientists decided to try the method with a different strain of HPV16, thinking that the reference strain might have some crucial difference that prevented VLP construction. They were right: the reference strain and the new strain differed by one amino acid that prevented accurate assembly.
Merck, under Maurice Hilleman’s direction, and MedImmune began to pursue commercial vaccine development from Lowy and Schiller’s ideas. Meanwhile, the scientist pair developed a test to measure antibodies to HPV16 triggered by VLPs in laboratory cells. The first HPV vaccine – a quadrivalent product protecting against two oncogenic and two wart-causing HPV types – was licensed in the United States in 2006. That same year, the Advisory Committee on Immunization Practices recommended that all adolescent girls receive the vaccine, a recommendation extended to boys in 2011.
The Lasker Awards program was created in 1945 by Albert and Mary Lasker to recognize fundamental biological discoveries and clinical developments that improve human health and to draw attention to the importance of public support of science.