Synagis and Beyfortus
Monoclonal antibodies for RSV in infants
After writing my RSV post the other day, it has come to my attention I didn’t cover all of the products recommended by the CDC to prevent RSV in children. I want to do a brief overview of that now.
The CDC recommends infant immunization through maternal vaccination between 32-36 weeks and there is only one vaccine on the market currently; Pfizer’s ABRYSVO which I covered in my previous post.
In addition to this, we have nersivamab (Beyfortus) recommended for children 8 months and younger as they enter their first RSV season and it is also recommended from 8-19 months to those children who are considered at increased risk for severe RSV entering their second season. [1]
Synagis is recommended to children 24 months and younger and is given once a month during the entire RSV season, which is “at least 5 months” long (usually from November through April). [2]
The CDC says, “To prevent severe RSV disease in infants, CDC recommends either maternal RSV vaccination or infant immunization with RSV monoclonal antibodies.” [3] This is my first time seeing this term being used interchangeably. The old school description of a vaccine was using either partial or whole cell, live or inactivated viruses or bacteria or toxin to incite an immune response that provides antibodies that will produce some sort of protection or immunity for some amount of time. In my experience “immunization” and “vaccine” are terms used very interchangeably, but they always meant essentially “to vaccinate with a vaccine.” Now we have monoclonal antibodies and the CDC is listing them under the heading of immunizations. That seems weird to me.
Both of these products are monoclonal antibodies and not vaccines.
***(Skip the next part if you aren’t interested in learning about monoclonal antibodies and how they work)
There are some similarities between monoclonal antibodies and vaccines but also some stark differences. Antibodies are found naturally in our blood and help us to fight infection. MAB (monoclonal antibodies) therapies mimic natural antibodies but are made in a laboratory. Monoclonal just means all one type. So each MAB is a lot of copies of one type of antibody.
This therapy is being used more and more frequently in treating cancer and I would love to think of it as an alternative to chemo. I think it’s usually given with chemo, but if we could truly make antibodies that effectively target only cancer cells without poisoning the rest of your body, how amazing would that be?
I first learned of this concept in my research on tetanus. Tetanus immunoglobulin seemed a much healthier and more effective alternative to a DTaP after potential exposure to tetanus (now, I wouldn’t do either one, but if forced to choose, the immunoglobulin makes more sense as it would act much faster than a vaccine and while it takes the latter 2 weeks to be considered effective, the average incubation period for tetanus is only 8 day). Immunoglobulin is made by taking antibodies from the blood of different donors and mixing it all together to create a shot that will hopefully provide a boost of protection in the days right after exposure.
Convalescent plasma operates under the same idea. Monoclonal antibodies are cloned in a lab instead of being harvested from donors and are much more target specific.
In Covid, people were given MAB when they first got sick. It wasn’t used as a prevention as much as helping people fight it off faster, but even that came with some risks.
“Researchers found that while the monoclonal antibody treatments were effective at reducing the risk of severe disease from COVID-19, the treatment significantly reduced the natural, quick responding IgM antibodies, particularly between 10 and 40 days after infection.” [4] So it hampered the body’s natural response and may decrease long lasting immunity.
These RSV products are the first time I’m seeing monoclonal antibodies being made to prevent an infection before exposure occurs. Normally, monoclonal antibodies are given IV and begin to work within an hour or so. They may not last very long but the main advantage is how fast acting they are. Whether that means less immunity later on, I don’t know, but I can see how it would be lifesaving to those at high risk from a certain infection.
However, they don’t last long. With tetanus, they are given in conjunction with a TDaP or DTaP booster and the main goal is to bridge the gap between the current time and the two weeks it takes for the vaccine to start producing antibodies that will last much longer. In Covid, MAB were given with the understanding that they would only last a few weeks. These are donor antibodies that circulate and hopefully do their job but this is passive immunity only and does not last long. It’s interesting that when I tried to find evidence of exactly how long they last online, there are many claims of “long term monoclonal antibodies” that last “many months” but very little data to support this claim. Some said that for Covid, it was 2-8 months, but the recommendation to receive a booster after 90 days flies in the face of that. If the MAB are specifically targeting spike protein it stands to reason that if they were still circulating and active, getting a booster would be an exercise in futility because as soon as your cells are programmed to begin making spikes, the MAB would swoop in and nullify this activity.
As early as February 2022, the recommendation to wait 90 days was removed and people were told they could get a booster “at any time”. [5]
I couldn’t find any studies to back up this stance, but I did find one where 2 doses of covid 19 vaccine were given 40 days after monoclonal antibodies and the antibody response to the vaccine was the same as those who had not received MAB. [6]
Another downside is that because they are so narrowly specific, if the virus mutates, it will evade the antibodies altogether. Omicron and beyond now evades this therapy almost entirely. [7]
So does the RSV virus mutate significantly?
“We have found that highly mutated surface attachment glycoprotein and fusion protein would make developing effective RSV A and B vaccines challenging.” [8]
****(for those who skipped the above, start reading again here)
Both Synagis and Beyfortus are given IM (intramuscular). Beyfortus is said to last 5 months, but Synagis obviously doesn’t last nearly that long as it is given once a month.
They do admit that monoclonal antibodies can cause severe side effects but the one I saw most was severe allergic reactions. I won’t be getting into side effects very much because other than allergic reactions I am not seeing a lot of data on anything else. That may change in the future as more and more children get this and the postmarking sections begin to populate, but for now, we don’t have very much to go on.
Beyfortus had 3 clinical trials before licensure, the first and second registering at 70 and 74.9% efficacy respectively. The third clinical trial wasn’t powered for efficacy. [9]
This is my favorite paragraph from the Synagis website:
“Remember, SYNAGIS is not a vaccine. Children can still get severe RSV disease despite receiving SYNAGIS. If your child has an RSV infection, make sure they continue to get their monthly injections throughout the RSV season—because babies can get RSV more than once.” [10]
In the first clinical trial mentioned by Synagis, they administered the drug 2:1 with 1,000 getting Synagis and 500 getting placebo. They did see a 55% decreased risk of hospitalization which was the primary endpoint of the trial, but for those who did end up in the hospital, “Overall, the data do not suggest that RSV illness was less severe among patients who received Synagis® and who required hospitalization due to RSV infection than among placebo patients who required hospitalization due to RSV infection.”
“In the IMpact-RSV trial, the incidence of anti-palivizumab antibody following the fourth injection was 1.1% in the placebo group and 0.7% in the Synagis® group.”
Wait what? The placebo group had higher antibodies than the Synagis group?
They explain this weirdness with, “These data reflect the percentage of patients whose test results were considered positive for antibodies to Synagis® (palivizumab) in an ELISA assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Synagis® (palivizumab) with the incidence of antibodies to other products may be misleading.” [11]
haha okay.
In conclusion I am neither for nor against monoclonal antibodies. I don’t think I would get it as a preventative but if I ever found myself in the hospital with a sick baby with RSV I would possibly consider getting the antibodies. Maybe.