CMV Vaccine Workshop Overview

CMV Vaccine Workshop Overview

Author: Hannah Hopkins Goldberg

I am proud to serve as an intern this Fall semester with the National CMV Foundation. I am learning quite a bit and have had an interest in learning more about CMV vaccine development. This internship was perfect timing, as I had the pleasure of partaking in included the NIH CMV Vaccine Workshop, CMV Vaccine Development: How Close Are We? held at the NIAID Conference Center September 27^th-September 28^th. While held in-person, there was a virtual attendance option. The purpose of the workshop was to discuss the lack of (and progress being made towards) a vaccine for the prevention of congenital cytomegalovirus (cCMV). This event was critical for the cause of the National CMV Foundation. I attended the second day of the workshop and was encouraged by the results presented by the speakers.
 
The day commenced with a brief history of CMV, orated by Dr. Stanley Plotkin. This lecture was essential and informative because it places the research presented in a historical context. Vaccine development has been ongoing since the 1970s and progress has not been linear. Briefly, CMV vaccine development began in the 1970s, and there was some minor success with the Towne vaccine. While the vaccine was safe and proceeded to human trials, it did not provide enough protection from a CMV infection. Since then, numerous vaccines have shown promise but have not been protective enough yet. Notable CMV vaccines from history include the Attenuated AD-169, the Towne vaccine, and the gB vaccine. Dr. Plotkin was optimistic about the future of CMV vaccination in light of the many vaccine candidates currently being researched and ended his session with the statement, “We will not fail.”
 
After this encouraging speech by Dr. Plotkin, Dr. Mark Schleiss gave an overview of novel CMV vaccine prospects. The vaccines currently in clinical trials in the United States are the mRNA-1647 vaccine (Phase 3 study on safety and efficacy that is currently recruiting), the V160 2 and 3 dose regimens (Phase 2 study on healthy females without a previous CMV infection), and a phase 1 study for gB and pentamer antigens that has already concluded. Dr. Schleiss also summarized many studies, but the most interesting ones to me were on the prospect of predicting which babies will have disabilities from cCMV through RNA sequencing or microbiome studies. A central point of his talk was that it is crucial that a biomarker is found that can predict adverse outcomes in babies so that care for these children can begin as soon as possible.
 
The first session of the morning was on CMV vaccine candidates and featured speakers from Moderna, QIMR Berghofer Medical Research Institute, VBI vaccines, Vir biotech, GSK, Université de Lausanne, and the Institute for Virology at the University Medical Center of Johannes Gutenberg-University. The key takeaway from this session was that there are numerous promising vaccines in development and that while the research is difficult, these research groups are dedicated to the creation of a vaccine for the eradication of cCMV.
 
Most notable from the first session were the talks by Dr. Lori Panther from Moderna and Dr. Hannah Alsdurf from GSK. Dr. Panther’s talk covered how close Moderna is to creating a CMV vaccine. She believes the mRNA 1647 vaccine is especially promising, and phase 1 and 2 trial results were encouraging. The vaccine has been shown to be safe and could be effective at preventing CMV. Dr. Alsdurf’s lecture was on the importance of diversity and inclusion in CMV vaccine trials. She stated that the trials need to be diverse in ethnicity and race as well as age, sex, gender identity, pregnancy status, and disability status, among other considerations. Trials performed by GSK in the past have not met census levels of representation for many groups, including Asian, Indigenous, Latino, and Hispanic people, while there is an overrepresentation of non-Hispanic white people. There has also been an issue with the retention of certain groups, such as Black/African Americans. Studies will start with this group represented but will lose participants as time continues. Through research, GSK has attributed this lack of representation and retention to numerous factors, including vaccine hesitancy. However, when a well-written educational intervention was presented to participants, there was greater retention and inclusivity. This study was important because cCMV can affect everyone, and studies should be diverse so they are representative of the population.
 
The next session was a discussion on whether or not a CMV vaccine could also act as an anti-cancer vaccine. This talk featured Dr. Kyle Walsh of Duke University, Dr. Jennifer Geris of Baylor College of Medicine, Dr. Joseph Wiermels of the University of Southern California, and Dr. Georges Herbein of the University of Franche-Comté in France. This was a lively discussion, and the main takeaway was that there is hope. It is possible that a CMV vaccine could prevent childhood leukemia, but more research is needed, especially on how the vaccine would affect T-cell immunity and immune system development in children.
 
The last main session of the day was on more CMV vaccine candidates. Of note was the talk by Dr. Don Diamond of the City of Hope Medical Center and Beckman Research Institute in California. Dr. Diamond explained the results of the phase 2 trials and how the results are better than they seemed initially. The CMV-MVA-Triplex Vaccine had about a 50% efficacy rate, but there was a large reduction in viremia (the amount of virus in the bloodstream), and the vaccine was not harmful to patients overall. He made a very good case for why this vaccine is worthy of further development and investigation.
 
Also of interest was the talk delivered by Dr. Gry Persson of Evaxion Therapeutics on utilizing artificial intelligence (AI) to develop a CMV vaccine. Evaxion, through the use of different AI models, proposes that they can develop vaccines much more efficiently than the traditional methods used by other labs. Their models employ available genomic and proteomic data to select which protein targets are the most promising for a vaccine. 
 
Overall, this workshop was a brilliant collaboration of some of the best minds in CMV research. It was evident that there are researchers all around the world working diligently towards an effective CMV vaccine. The workshop is a beacon of hope that a vaccine for the prevention of cCMV is perhaps nearer than we think.