Schleiss Mark
Biography
Dr. Mark R. Schleiss is the American Legion and Auxiliary Heart Research Foundation Professor of Pediatrics at the University of Minnesota Medical School. Dr. Schleiss completed residency, fellowship and post-doctoral training at the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, Washington. His laboratory, funded by grants from the NIH and CDC, studies cytomegalovirus (CMV) vaccines in preclinical models. Results from vaccine studies in his novel guinea pig model of transplacental infection have helped to inform and direct the human vaccine discussion. He is currently conducting a study of universal congenital CMV (cCMV) screening in Minnesota in collaboration with the CDC and Minnesota Department of Health. He advocated for universal cCMV screening legislation, the “Vivian Act”, which was successfully passed in Minnesota in 2021. As a result of this legislation, Minnesota will be the first state in the USA to conduct universal cCMV screening. He is a former Secretary-Treasurer of the Society for Pediatric Research and is currently a member of the Minnesota Chapter of the American Academy of Pediatrics Board of Directors. As a board-certified pediatric infectious diseases specialist, his work spans “bench-to-bedside” exploration of issues relevant to pathogenesis, immunity, and clinical management of cCMV infection.
Keynote Lecture Abstract
CMV Vaccines: An Overview
A vaccine against congenital cytomegalovirus (cCMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, and by evidence that pre-conception maternal seropositivity does not fully prevent recurrent maternal infections with subsequent fetal transmission. Although knowledge deficits exist, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. Platforms currently in various stages of clinical trials include adjuvanted protein subunit vaccines and mRNA vaccines, both based on expression of the immunodominant glycoprotein B and pentameric complex of CMV; disabled, infectious single-cycle vaccines; vectored vaccines utilizing recombinant LCMV and MVA systems; and eVLP vaccines. Innovations rapidly approaching the clinic include nanoparticle vaccines and strategies based on expression of the pre-fusion conformation of fusogenic envelope glycoproteins. In the face of the knowledge that up to 60,000 infants are born with congenital CMV in the United States and EU every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. The need is even greater in the developing world, where birth prevalence is higher. The status of CMV vaccines in clinical trials, and a perspective on the requirements for a CMV immunization program to become incorporated into clinical practice, will be provided.
Neonatal Screening: Translation of Research to Policy
Many states in the United States have pursued legislative solutions to solve the unmet need for congenital CMV (cCMV) screening. In 2017, a parent-lead initiative was commenced to add cCMV screening to Minnesota (MN) law. House Bill HF2653 (the “Vivian Act”), was introduced in the MN legislative session. After several committee hearings, a press conference (https://www.youtube.com/watch?v=qEc0jncqBQQ), and input from the MN Department of Health, the legislation was tabled. Between 2018-2020, the legislation was re-introduced three times, but pressing priorities conferred by the emerging Covid-19 pandemic precluded the bill’s advancement.
In 2021, a re-configured bill was introduced for universal cCMV screening and successfully passed. These efforts were facilitated by results from an ongoing study I direct in Minnesota, in which we have screened >25,000 newborns for cCMV since 2017 (doi:10.1001/jamapediatrics.2020.5441). This research demonstrated a prevalence of cCMV of 0.4% in Minnesota, with an analytic sensitivity of PCR of the newborn dried blood spot (DBS) of 85%. A striking impact of the Covid-19 pandemic on the prevalence of cCMV was observed (doi:10.1001/jamanetworkopen.2022.30020). Data on prevalence, epidemiology, and clinical consequences of cCMV will be presented, as well as information regarding neuroimaging, antiviral therapy, and long-term sequelae. The legislation required the state’s Newborn Screening Advisory Committee (NSAC) to review cCMV for addition to the state’s newborn screening panel, planned for implementation in 2023. This addition makes Minnesota the first state in the USA to screen all newborn for cCMV infection. An overview of the DBS universal screening program planned for 2023 will be presented.
