Robert C. Rose, Ph.D.

Research Bio

Genital infection with any of several human papillomaviruses (HPVs) is necessary but not sufficient to cause uterine cervical cancer, the second most common female malignancy worldwide. In the late 1980s we established antibody-mediated virus neutralization as a vaccine concept for prevention of genital HPV infections by using authentic virions of a genital HPV type (type 11 or "HPV11") to demonstrate that viral infectivity could be blocked with capsid-specific antibodies. This observation led us to produce non-infectious "virus-like particles" (VLPs) of prevalent genital HPV types associated with either benign genital warts (HPV11) (1) or cervical cancer (HPV16 and HPV18) (3). By comparing HPV11 recombinant VLPs with authentic native genital HPV11 virions, we were able to show that VLPs accurately mimic viral structure and immunological properties. We then formally demonstrated that this approach to vaccine development was valid by showing that antibodies raised against HPV11 L1 VLPs efficiently neutralized authentic HPV11 virus particles (2).Our subsequent evaluations of antibody responses against VLPs derived from three genetically distinct genital HPV types (i.e., types 11, 16 and 18) led us to conclude that antibody-mediated neutralization was genotype-specific, and that multivalent HPV VLP vaccine formulations would be required for the induction of broadly protective immunity against genital HPV disease (3)(4).