When it comes to Covid-19 boosters, should you stick with the vaccine type that got you to the prom, so to speak? Or is mixing it up the way to go?

That may be the question that you’re facing right now, assuming that you’re 18 years of age or older and human. The Centers for Disease Control and Prevention (CDC) recommends that you get a booster dose if you’ve already gotten your full primary vaccination series and enough time has elapsed since then. That would be six months (or about 18 Scaramuccis) after you got the second dose of the Pfizer-BioNTech or Moderna Covid-19 mRNA vaccine and two months (about 6 Scaramuccis) after the first dose of the Johnson & Johnson (J&J) vaccine.

So do you treat your booster and primary vaccination like a velour tracksuit and make sure that everything matches? Or should you try something completely different when it comes to the booster? In other words, is it better to mix and max vaccine types so that the booster is different from the primary vaccination, otherwise known as heterologous boosting?

Well, more of the same is not a bad idea. Most of the available data on boosters is from ongoing clinical trials that have been using the same brand of vaccine for all doses. For example, a study published on October 7 in the New England Journal of Medicine compared those in Israel who had gotten two doses of the Pfizer-BioNTech Covid-19 vaccine with those who gotten the two doses plus a third dose of the Pfizer-BioNTech Covid-19 vaccine as a booster. Those in the boosted group were 11.3 times less likely to get infected with the Covid-19 coronavirus and 19.5 times less likely to have severe Covid-19 than those in the un-boosted group.

And Pfizer and Moderna have each announced that preliminary data suggest that three doses of their vaccines seem to offer good protection against the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), according to this CNBC news report:

Take these announcements with a bucket hat full of salt since they are from the pharmaceutical companies rather than independent scientists, the findings are preliminary, and the data has not been fully shared with and vetted by the larger scientific community.

There is comparatively much less data on what may happen when you mix and match booster shots in different ways. One study described in a pre-print recently uploaded to MedRxiv looked at all nine possible primary plus booster combinations of the three Covid-19 vaccine brands available in the U.S. The research team that conducted the study included investigators from the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH), the Baylor College of Medicine, the University of Maryland School of Medicine, the Emory University School of Medicine, the University of Washington, the University of Pittsburgh School of Medicine, and various other academic institutions. The study consisted of 458 participants divided into nine roughly equal-sized groups with each group getting a different primary plus booster combination. This meant that approximately 50 participants were in each group.

Now 50 is not a big number unless you are talking about marmots in your bed or hot dogs in your mouth. It may not be large enough to account for other differences that could exist among the different participants. For example, the research team did not determine which study participants may have had previous SARS-CoV-2 infections and the severity of such infections. The researchers did not randomly assign participants to the different groups to smooth out potential differences among participants. Plus, a pre-print is not the same as a peer-reviewed publication in a reputable scientific journal. Anyone with a computer, access to the Internet, and opposable thumbs could in theory upload a pre-print. So take anything from this study with a fanny pack of salt.

The study focused on antibody levels. The research team checked the levels of binding and neutralizing antibodies in the participants’ blood before and after each had gotten his or her respective boosters. Neutralizing antibodies are ones that can essentially deactivate portions of the virus used to infect your cells. Some antibodies are considered non-neutralizing antibodies and can bind parts of the virus without interfering with the virus’s ability to infect your cells.

Here’s the good news from the study. All booster-primary vaccination pairings resulted in higher levels of binding and neutralizing antibodies. None of the participants suffered any serious adverse events from the boosters. No one died, developed new onset chronic medical conditions, or turned into a dog from the boosters through study Day 29. (The two reported severe adverse events seemed unrelated to vaccination.) Of course, there is no absolute guarantee that someone won’t turn into a dachshund down the road. Heck, there is no absolute guarantee that eating a hot dog won’t turn you into a dachshund. But such effects would be highly, highly, highly unlikely since the vaccine components don’t stay in your body that long and the word “wiener” can mean different things in different contexts. Most side effects occurred within three days of the booster and were similar to the types of side effects seen for primary vaccination. Side effect rates were similar across the different boosters.

The study results did suggest that the Covid-19 mRNA boosters (either Pfizer-BioNTech or Moderna) may produce a stronger antibody response than the J&J booster. Boosting with the mRNA vaccines resulted in at least a two-fold increase in binding antibodies for nearly all of the participants regardless of the type of primary vaccination that was given. Those who had received the J&J vaccine for primary vaccination had a 33-fold rise in antibodies after the Pfizer-BioNTech booster and a 56-fold increase after the Moderna booster. Among those who ended up getting the J&J booster, those who had had the J&J primary vaccination achieved seven-to-10 fold lower binding antibody levels than those who had had a mRNA primary vaccination. Getting a mRNA booster vaccine resulted in at least a four-fold increase in neutralizing antibodies more often than getting the J&J booster vaccine.

Now, the study results also suggested that the Moderna booster may give a slightly stronger antibody response than the Pfizer-BioNTech booster with an emphasis on the word “may.” So, based on this study’s results, perhaps, possibly, maybe, potentially three doses of the Moderna Covid-19 mRNA vaccine may give you the strongest antibody response of all the nine possible primary plus booster combinations. A close second could be the two-dose Pfizer-BioNTech for primary vaccination followed by a Moderna booster. Third may be the two-dose Moderna primary series with the Pfizer-BioNTech booster. Again take all of this with an Ugg boot full of salt.

It wouldn’t be a complete surprise if the Moderna vaccine were to generate somewhat stronger antibody responses on average since a Moderna vaccine dose is a larger 100 μg compared to the Pfizer-BioNTech’s 30 μg vaccine dose. In other words, this is one situation where size may matter.

Size ain’t everything, though. Personality matters too, right? And when it comes to immune protection, antibody levels aren’t everything either. It is just one set of measures and does not account for other ways your immune system can protect your body such as T cell responses. Therefore the study couldn’t say anything about how different boosters may affect other aspects of immune protection.

The study didn’t check length either. Length of the immune protection offered, that is. It’s not clear whether certain primary plus booster regimens may result in a longer duration of immune protection against the Covid-19 coronavirus. In fact, it’s not yet clear how long protection from any of the boosters may last. Unless you have made a time machine out of a DeLorean, the quantum realm, or a hot tub and can look into the future, no one can tell how long immune protection from boosters may end up lasting.

Another caveat is that the study used the 100 μg dose of the Moderna Covid-19 vaccine as a booster. The 100 μg dose is what’s currently used for primary vaccination. However, the U.S. Food and Drug Administration (FDA) has authorized a smaller 50 μg dose for the Moderna booster. So your antibody boost from the Moderna vaccine may not be as great as what was observed in the study.

Finally, the study size and follow-up time weren’t large and long enough to capture all possible rare side effects. To date, serious side effects have been rare for primary vaccinations. Nothing suggests that such side effects may be more common for boosters than they are for primary vaccination. And in case you are wondering, there is no evidence that Covid-19 vaccines will alter your DNA, increase your 5G reception, make keys stick to your forehead, or cause you to grow an extra arm. Being fully vaccinated and boosted may make you more attractive on Tinder, though, which may or may not be a good thing.

Nevertheless, the study offered good news in general. All of the combinations and all of the Covid-19 boosters seem to be decent choices. None of the boosters are like buying a pair of inflatable balloon trousers and then losing the receipt. Chances are you won’t have buyers remorse and end up thrusting your hands to the sky in the future and saying, “why, oh why did I choose that booster?” All should give you a good boost to your immune protection.

Ultimately, what may matter more is availability. Consider getting whatever type you can get the soonest. In other words, you may want hook up with the first one that you can find. Such an approach shouldn’t necessarily apply to everything you do in life like dating and buying underwear. Nonetheless, there is a reason to take this approach for the booster. The longer you go un-boosted, the longer you’ll go without optimal protection. With the weather getting colder and drier, activities moving indoors, and all the Holiday travel, the next few months could see a Winter surge in Covid-19 as I have covered for Forbes. You’ll probably want to protect yourself as much as you can during this time rather than wait for a particular booster.

Furthermore, keep in mind that the immune protection offered by the primary vaccination plus the booster may vary from person-to-person. A study may provide averages and ranges but may not necessarily predict what specific level of protection you’ll receive. So what may be the “optimal” booster shot for one person may not be the optimal one for another.

Even after getting boosted, try to maintain other Covid-19 precautions as much as you can such as face mask use and social distancing as long as the virus remains widespread around you. The booster plus primary vaccination is not like wearing a concrete full body condom and then pouring some extra cement on it. It won’t offer 100% protection. The protection offered by the booster plus primary vaccination will depend on how many other precautions you are layering on as well. After all, you wouldn’t go out into the cold wearing just your velour tracksuit would you?

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