Stanley Plotkin: the bright spark of cytomegalovirus vaccines.

Abstract

Dr. Plotkin probably never envisaged a lifelong courtship with CMV vaccine initiatives when he began investigating CMV some 45 years ago. His initial focus was, of course, the live-attenuated Towne vaccine, which he escorted through clinical development that included: (1) the demonstration of safety and efficacy in solid organ transplant recipients [1], (2) the hallmark demonstration that the vaccine strain was unable to reactivate and so lacked the biological property of latency [2] and (3) a test of safety and efficacy against experimental challenge with the limited-passage Toledo strain [3]. He chose to recruit Catholic monks as vaccinees; thus, eliminating any risk for pregnant women or children after infectious challenge with the Toledo strain. These important milestones in the 1970s and 1980s engaged many talented associates and envisaged eventual success for this vaccine strategy. His research led to the first contemporary concepts of CMV vaccination, including the importance of cellular immunity to the conservation of protective antigens among circulating strains and the benefit of natural and experimental challenge [3–5]. These concepts challenged the conventional confidence in antiviral antibody as the sole mediator of immunity, a theme that continues to be debated today. Along the way, his report of a vaccine efficacy against CMV-associated opportunistic disease in solid organ transplant recipients [1] was an accomplishment as the first success of a vaccine for an opportunistic infectious disease. Ultimately, Towne vaccine was effective in kidney transplant patients, but proved less potent than natural infection in women of childbearing age when they were evaluated for resistance to natural mucosal acquisition of virus [6]. These studies portrayed an opportunity that has been pursued with other vaccine strategies, both live and nonlive, while Towne vaccine has been sidelined. Whereas over the years he dedicated his research enterprise to establishing a CMV live-attenuated vaccine It is a tremendous pleasure and indeed honor for me to introduce Dr. Stanley Plotkin, a living legend in the world of vaccines, who will present a personal view of the current state of affairs in cytomegalovirus (CMV) vaccine development (Fig. 1). Dr. Plotkin, more than any other individual, has contributed to the progress in vaccine research and development since the idea of universal vaccination to prevent CMV congenital disease was proposed nearly 50 years ago. After completing his medical training just about the time CMV was first isolated and following a few years working for the Centers for Disease Control in the Epidemic Intelligence Service, from 1960 to 1991, he directed a vaccine research group at the Wistar Institute and maintained clinical affiliations with the University of Pennsylvania and Children’s Hospital of Philadelphia. Dr. Plotkin is most renowned and recognized for his pioneering work on viral vaccines. His research expanded the portfolio of children’s vaccines currently available to combat widespread infectious diseases, including rubella, polio, rabies, rotavirus diarrhea and varicella (chicken pox). His success in the development of a live-attenuated rubella vaccine, currently in use worldwide, prompted a follow-up focus to address the need for a CMV vaccine, most likely due to the many common attributes between German measles-associated congenital disease and patterns of CMV disease, despite their marked differences in biology.