Two of the three COVID-19 vaccines available in the U.S. right now require two doses spaced several weeks apart. But could Americans ultimately need a third vaccine shot? In this Motley Fool Live video recorded on March 3, 2021, Fool.com contributors Keith Speights and Brian Orelli discuss how new coronavirus variants could increase the likelihood that another booster shot will be required.

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Keith Speights: Pfizer (PFE -1.05%) and BioNTech (BNTX 0.07%) announced last week that they are testing a third vaccine shot as a booster. What they're doing is they're trying to see if they could increase protection against the new coronavirus variants. The companies are also talking with the FDA and other regulatory authorities about potentially conducting yet another clinical study to evaluate a version of their vaccine BNT162b2, to specifically target that variant that was first identified in South Africa, it's called B.1.351.

Brian, what do you think the chances are that Americans are going to end up needing to have a third vaccine shot?

Brian Orelli: It's probably pretty likely with the variants running around. In terms of these two strategies, they are interesting. If you just take the third coronavirus vaccine, just add more vaccine, that will boost total number of antibodies that we have running around our body and the immune system's memory so that it will ramp up quicker the next time you actually got infected. That's probably useful, if the vaccines aren't as effective on the variants because the variants were able to replicate faster in the body or infect cells faster in the body then you can imagine just having more antibodies around would be a good thing.

If the problem is not that they're less affected because they're replicating faster, but because there's mutations, and we now don't have any antibodies to those specific parts of the coronavirus, they have those new mutations that are in the variance, then developing a third booster shot that uses the variance as what's the immunogenic part of the vaccine, then that would be most effective.

Which one of these two strategies will work? Probably depends on whether the vaccines aren't as effective on the variants because either the viruses are replicating too quickly or because there's too many mutations, and now we don't have antibodies to that part of the coronavirus.

Speights: That doesn't sound great, Brian. We might have to have three shots. Johnson & Johnson (JNJ 0.22%), single-shot dose, right? I'm not sure what their plans are. But have you heard anything about what Johnson & Johnson might be doing?

Orelli: They're definitely testing a second shot.

Speights: Yeah, right.

Orelli: Whether they want to get into a third shot, [Laughs] they've got to figure out whether a two-shot is better than one.

Speights: Yeah.

Orelli: If they can prove that two shots are better than one then maybe they go and test a third shot. Again, we've talked about variants before, but the mRNA vaccines are a lot more likely to be more effective with the booster shots than adenovirus-based vaccines because there are no viruses, it's the virus itself.

So in addition to creating antibodies to the coronavirus, the protein that gets expressed by you have no virus. You are also developing antibodies to that adenovirus. So the adenovirus-based vaccine are going to become less and less effective as you do more and more doses.

Speights: Yeah. I'm not sure if Johnson & Johnson has come out and stated specifically that they're trying to target the new variants. Like I said, specifically, Pfizer and BioNTech are doing so, Moderna's (MRNA -0.34%) doing so, Novavax (NVAX -2.51%) is doing so, not sure about J&J. So we will see, we just might have to have that third shot if you're right, Brian.