Trial for CMV vaccine seeks women of childbearing age

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Starting this summer, all babies born in New York State will be screened for congenital cytomegalovirus. And this is happening coincidentally at a time when Upstate researchers are recruiting women of childbearing age into a study of a vaccine that could prevent congenital CMV. I'll cover all of this with my guest, Dr. Joe Domachowske. He's a professor of pediatrics and also of microbiology and immunology, and he specializes in pediatric infectious disease. Welcome back to "HealthLink on Air," Dr. Domachowske.

[00:00:46] Joe Domachowske, MD: Thanks, Amber.

[00:00:47] Host Amber Smith: Now let's start with some background on CMV. What can you tell us about cytomegalovirus?

[00:00:53] Joe Domachowske, MD: It's another one of those viruses that's so common, but not everyone's heard about it. It's in the community because young children shed a lot of this virus in their saliva and their urine based on a previous infection that they've had.

[00:01:08] Host Amber Smith: Is it dangerous for people to contract?

[00:01:12] Joe Domachowske, MD: In otherwise healthy, younger people it's not dangerous, but the problems that can occur mostly happen in pregnant women, when they become infected -and the risk is to their growing baby - and in immunocompromised individuals,people who have needed treatment for cancer, for example, or have had a transplant.

[00:01:33] Host Amber Smith: Once someone is infected with CMV, does a healthy person's body get rid of it, or does the virus stay with us?

[00:01:43] Joe Domachowske, MD: No, this is one of those herpes-like viruses. It's in the big herpes family. And just like the cold sore viruses, CMV can come back and reactivate. It's just usually very asymptomatic, so we don't even know when we're shedding CMV, unlike a cold sore where you can see it and feel it.

[00:02:03] Host Amber Smith: If CMV is so prevalent in society, is there any way to avoid being infected, or are we all going to be exposed?

[00:02:11] Joe Domachowske, MD: The vast majority of individuals, more than 70%, are exposed and infected by the time they're in their 50s to 60s. About 40% are infected during young childhood.

So the best way to prevent infection altogether is good hand washing. And we know that, especially when you're taking care of young kids who may be shedding the virus. That's where most of the contagious virus is.

[00:02:34] Host Amber Smith: Are there effective treatments for people that are infected and that this is causing problems for?

[00:02:40] Joe Domachowske, MD: Yeah, there are nice antiviral medications for very serious infections and compromised individuals that we can fall back to. The vast majority of people don't need treatment for this because it's not going to cause them much harm.

[00:02:55] Host Amber Smith: Now, New York State is adding congenital cytomegalovirus to its screening panel for all newborns. Is that a simple blood test that will be added to the other blood tests that are done routinely at birth?

[00:03:08] Joe Domachowske, MD: Right. So every state has a newborn screening program. And in New York State that involves taking some blood from the heel stick of each of the babies to put it onto filter paper. The filter paper is allowed to dry, and then it's sent to Albany to the New York State Department of Health laboratory at Wadsworth. Those pieces of paper are then tested for a number of different metabolic problems, for HIV and now coming forward for CMV, because we can do something with those results that may be beneficial for the babies.

[00:03:41] Host Amber Smith: Now without a blood test, how would a parent know that their baby was infected with CMV? Are there symptoms for newborns?

[00:03:49] Joe Domachowske, MD: Only 10% of babies will actually have symptoms suggesting that they had a congenital infection. Ninety percent are completely asymptomatic. But because all of them are at risk for hearing loss, both hearing loss detected at birth if we test for it, and having progressive hearing loss over that first year of life, we need to know which babies are infected because we can treat them and prevent the hearing loss from happening altogether.

[00:04:17] Host Amber Smith: So the hearing loss is tied to the virus, in babies?

[00:04:21] Joe Domachowske, MD: Yes. And if it's not treated and controlled early on, that hearing loss can worsen over time. About 50% of those that have no hearing loss at all at birth, where we do newborn testing for hearing -- we actually do that now as a law in New York State -- those that fail the newborn hearing test, if it's because of CMV, half of them will go on to have more progressive hearing loss, so it gets worse over time.

[00:04:48] Host Amber Smith: I was going to ask you about the potential longer term health consequences, but it sounds like hearing loss is one of them.

[00:04:55] Joe Domachowske, MD: That is the major one. More serious things can happen to the fetus, and we know about those when they're born because they have clinical signs and symptoms of congenital infection. And those babies we can often treat with the antiviral medications and improve their long-term outcome. But the damage that's already been done, we can't reverse.

[00:05:17] Host Amber Smith: Now, I don't know if you'll know this, but if an older person is infected with CMV, will that impact their hearing ability?

[00:05:25] Joe Domachowske, MD: It's unlikely, because it's thought to happen during developmental stages of hearing, growth and development, which is mostly before birth, but some of those steps happen after the baby is born.

So, hearing loss is not a major consequence for compromised individuals who develop CMV infection, but they have a whole long list of other things that they can get into trouble with.

[00:05:49] Host Amber Smith: Well, what will happen if the blood test reveals a CMV infection in a newborn?

[00:05:55] Joe Domachowske, MD: So the New York State newborn screening test, if that comes back positive for CMV infection, all the babies in the region will be referred to our center, and one of the five infectious disease specialists in our group will see and evaluate the baby and talk with the family about the risks associated with hearing loss, check for other signs or symptoms that may not be obvious. We'll do some imaging studies to make sure the brain development was OK. We'll do some blood tests to make sure that the blood counts look OK, and then have a discussion about whether or not they would consider antiviral therapy for a period of time, either six weeks or six months depending on the findings of all the screening work we do.

[00:06:37] Host Amber Smith: What percent of babies do you suspect will test positive for CMV?

[00:06:43] Joe Domachowske, MD: So in New York State, it's about 1% total. We have a birth cohort of roughly a quarter million babies per year. We know that certain ethnicities are more likely to be affected by congenital CMV infection. Black babies and other babies of color are more likely, it's about 1% of all of those infants will be infected. But for Hispanic ethnicity and for Caucasians, it's about half of that, maybe a little bit less.

[00:07:17] Host Amber Smith: Is there anything that the routine pediatrician will need to do differently for a CMV positive baby going forward with their primary care?

[00:07:28] Joe Domachowske, MD: The law is built to try to simplify the referrals as much as possible. So the New York State Department of Health, anytime they have a positive newborn screen result, they contact the referral centers, if it's a metabolic disease, for example. Our group will see all the babies with possible HIV, CMV and severe combined immune deficiency. So that should happen automatically.

But as a built-in safety step, the pediatricians or primary care doctors are also made aware. They receive the report themselves, and there's information on the report: This baby should be referred to one of the following groups for this particular problem.

[00:08:10] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith. I'm talking with Dr. Joe Domachowske about cytomegalovirus.

Now, you and your team are working toward developing a vaccine that would offer protection against CMV, is that right?

[00:08:26] Joe Domachowske, MD: That's right.

[00:08:27] Host Amber Smith: So what can you tell us about where things stand with that?

[00:08:32] Joe Domachowske, MD: Things are progressing quickly. We have finished phase two trials and phase three trials, which are the large trials, looking at always safety, but the possibility of efficacy to prevent congenital CMV in babies born to infected moms when they're infected during pregnancy.

Phase three is an RNA vaccine, just very similar to the RNA vaccines that were developed for prevention of Covid-19. And it appears that this is the strategy that's most likely to work. It's progressing quick. We are in enrolling individual females between the ages of 16 years and 40 years who are otherwise healthy and who are negative when screened for prior infection with CMV.

So the first step is to draw the blood and see if they've already been infected with CMV. At this point for this trial, they would be excluded from the current study. But if they're seronegative, meaning negative antibody testing, then we can go forward, enroll them. They get either a placebo for three doses of the vaccine, or they get three doses of the vaccine itself, and we follow them for two full years. If they get pregnant, we follow their babies even longer than that.

[00:09:47] Host Amber Smith: So the way this vaccine would work, then, the moms would be vaccinated, ideally before they become pregnant so that they wouldn't infect their unborn babies?

[00:09:59] Joe Domachowske, MD: To reduce the possibility of infecting the babies when they do become pregnant. Because even prior CMV infection, there's a very low risk, but prior CMV infection, if it reactivates during pregnancy, the virus can get into the blood and cross the placenta and infect the baby. That happens much less commonly than if the mother's infected for the first time. So we're trying to prevent that first time infection altogether.

[00:10:26] Host Amber Smith: So this vaccine wouldn't help the baby, per se, later, like after the baby's born, this doesn't offer that baby protection against CMV, or does it?

[00:10:37] Joe Domachowske, MD: No. If this vaccine works as designed and as expected, then the end goal here is to prevent congenital infection and the hearing loss and other consequences that can be associated with congenital CMV infection.

But it will also sort of paved the way for an active vaccination to give to individuals who are either known to be at high risk for acquired CMV after birth, because they're prepping for cancer therapy or they need a transplant, something like that. Right now we do not have any way to prevent CMV from a vaccine side in those higher risk groups, even if we know that they're at very high risk.

For example, a transplant patient who we know is negative antibody for CMV, they've never been infected before. But we're going to give them an organ, a kidney, or a liver or something else, from a donor who we know is CMV positive. CMV is going to be present in that organ. And so we know those individuals are extremely high risk for a CMV type disease, and we have to control it with medication.

It would be great if we could vaccinate them ahead of time knowing that we're going to place them at increased risk.

[00:11:52] Host Amber Smith: What can you tell us about previous potential CMV vaccines?

[00:11:57] Joe Domachowske, MD: Very simple, and one line: They didn't work.

[00:12:00] Host Amber Smith: So these are the mRNA. It's a different approach, it sounds like.

[00:12:04] Joe Domachowske, MD: Yes. And one of the benefits of the mRNA vaccine, probably the reason why it works, is that the RNAs that enter the cells, they create the protein itself, the CMV protein that acts as the immunizing agent. And one of the immunizing agents that's so important is a very large molecule. It's actually five different molecules of the same thing that come together and form a macro, a very big molecule.

And when that happens and the protein is made inside the cell, those five pieces self-assemble, almost like they're trying to make the virus itself, but they can't because they don't have the rest of the machinery. But those five proteins come together and make the molecule that's needed and then they get kicked out of the cell and function as an immunizing agent.

We don't have a good way to do that otherwise because it's not a stable enough protein confirmation to make in a laboratory. So we use our own cells to do it.

[00:13:05] Host Amber Smith: So for the trial that you're doing now, how many people are you looking for?

[00:13:11] Joe Domachowske, MD: We have screened about 40 women between the ages of 16 and 40 years of age. About half of them were antibody negative, so we've started vaccinating 20 individuals. We will continue to enroll patients, research subjects, until the end of October of this year, unless the study fills before then.

The sponsor, Moderna, they're particularly interested in having more 16- to 18-year olds enrolled in the trial because there's not very many of them so far. So we're looking at adolescents and the younger adults that have maybe been in other trials we've done to see if they might be interested. And we've had really good success. We're screening four or five individuals each week.

[00:13:56] Host Amber Smith: Are other sites participating, or is it just in Syracuse?

[00:14:00] Joe Domachowske, MD: This is both multi centered in the US and international, so there's both US and global sites. The total enrollment that's needed to try to address the question is about 15,000 individuals, knowing that only about half of them will actually be eligible for receiving the vaccine.

[00:14:20] Host Amber Smith: So if a listener is interested, is there a phone number or a website where they could learn more or sign up?

[00:14:27] Joe Domachowske, MD: Yes. We have a single phone number that we can use to one call, one person. If the person doesn't answer the phone, just try again. Leave a message. We'll get back to them right away. It's (3 1 5) 8 0 2 - 1 1 0 5.

[00:14:44] Host Amber Smith: Now are participants compensated for participating?

[00:14:49] Joe Domachowske, MD: Yes. We compensate everyone who is screened and enrolled for onsite visits. In addition, there is compensation provided for an e diary, an electronic diary where they fill out information about any signs or symptoms that they have experienced about a week or so after each of the three doses.

[00:15:10] Host Amber Smith: So there'll be generally three site visits over the course of, did you say, two years?

[00:15:15] Joe Domachowske, MD: Oh, many more than that.

[00:15:17] Host Amber Smith: Oh, OK.

[00:15:17] Joe Domachowske, MD: Three site visits involve vaccine or placebo injections, but we see them regularly. It's about every month for the first six months of the study, and then they're spaced out. I think it's a total of about 14 visits overall.

[00:15:31] Host Amber Smith: Now, at this stage in the trial, though, this substance has been found to be safe to use in humans, is that right? Or are there any risks that people should be aware of?

[00:15:42] Joe Domachowske, MD: This particular vaccine formulation has been determined safe in phase one and phase two trials, which represent a couple of thousand young adult women. But we know much more about the mRNA platform safety profile from the Covid vaccines. And it's exactly the same platform that Moderna used for their Covid vaccine. So, w we have a lot of information. Much of the side effect profile relates to the lipids, these nanoparticles that are used to protect the RNA that are the immunizing portion of the vaccine. So we know that's the case, and the mRNAs themselves don't really contribute to the safety one way or another.

[00:16:24] Host Amber Smith: Well, Dr. Domachowske, thank you for making time to tell us about this. I appreciate it.

[00:16:29] Joe Domachowske, MD: Yes. Thanks for giving me the chance to tell you about all these things. It's an exciting time for CMV.

[00:16:34] Host Amber Smith: My guest has been Dr. Joe Domachowske. He's a professor of pediatrics and also microbiology and immunology, and he specializes in pediatric infectious disease. And if you're interested in learning more about the CMV trial, the phone number to call is (315) 802-1105. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.