VYD2311 Safety in High-Risk Groups: Michael Mina, MD, PhD

Invivyd's investigational monoclonal antibody VYD2311 showed superior safety and tolerability compared with the mRNA-based COVID-19 vaccine Comirnaty in the phase 3 LIBERTY study.¹

In part 1 of this interview with The American Journal of Managed Care^® (AJMC^®), Michael Mina, MD, PhD, chief medical officer and chief epidemiologist of Invivyd, discusses which adverse events drove the difference between VYD2311 and the vaccine and why he expects the findings to extend to the higher-risk populations who are often the focus of COVID-19 prevention.

This interview has been edited for clarity and length.

AJMC: Within 6 days of dosing, 56.5% of participants who received VYD2311 had a treatment-emergent adverse event, injection site reaction, or hypersensitivity reaction, compared with 91.4% of those who received the vaccine. What kinds of events drove that difference? How should clinicians interpret it when VYD2311 and the vaccine work through different mechanisms?

Mina: We looked at a number of different treatment-emergent adverse events, and I would say one of the biggest findings was actually that there was a much lower rate of individuals with injection site pain. So that might be swelling, pain in the arm, redness, or tenderness. That was actually somewhat surprising to us. We get a lot of questions because, to give the monoclonal antibody, it's a larger volume of fluid compared with the vaccine. It's 0.5 mL in a vaccine and 2 mL in the monoclonal. So the question is: Would 2 mL potentially cause more pain?

That was actually an area where we saw the greatest delta, meaning we saw a significant reduction in injection site pain when given a monoclonal compared with a vaccine. That probably has to do with the fact that a vaccine is driving an inflammatory response at the site of injection, whereas a monoclonal is much more of a passive, directly immunizing approach, where there is no real inflammation at the site of the injection.

So that was one of the biggest ones. We also saw reductions in fevers, chills, and fatigue. These were some of the major areas where we look at treatment-emergent adverse events, and we see a lower fraction of recipients receiving the monoclonal having these types of events compared with those receiving the vaccine.

AJMC: LIBERTY enrolled healthy adults aged 18 to 49 years. How well do you expect these safety findings to carry over to older adults, immunocompromised patients, and others at higher risk of severe COVID-19, who are often the focus of prevention efforts?

Mina: From the safety and tolerability aspect, we expect that there will really be no difference. When we look, for example, at some of our preexisting data from CANOPY, which was the phase 3 trial that looked at pemivibart, the current medicine that's on the market [under emergency use authorization] for pre-exposure prophylaxis from Invivyd—and the molecules are very, very similar between pemivibart and the investigational drug we're talking about today, which is VYD2311—when we look at the results from the CANOPY trials and prior to that the EVADE trials, we don't anticipate seeing major differences between the age categories or between immunocompromised and non-immunocompromised individuals, for instance.

So we expect that what we have now identified in LIBERTY will probably map very well onto older age categories of individuals, immunocompromised individuals, and otherwise.

One of the other things to consider is just the existence of a monoclonal and how monoclonals and vaccines might work together, particularly for older individuals, individuals with comorbidities, or individuals who have any sort of immune compromise. Currently, there are not many pre-exposure prophylactic medications. There are no preventive medications outside of the vaccines, and unfortunately, older individuals and individuals who are in an immunocompromised state are both the individuals at highest risk for COVID-19, and simultaneously, they're also the individuals least able to respond well to a vaccine.

So for individuals who are older or who are immunocompromised, these are precisely the individuals who, at the same time, have the greatest risk for severe COVID-19 and also have the least ability to respond very well and durably to current vaccines. A monoclonal antibody does not require the immune system to turn on and to be fully engaged in order to do its work. It gets injected, and it starts working.

So this is where we think that, particularly for older individuals and immunocompromised individuals, offering something that is not an active immunization that requires all of the proper mechanisms of the immune system to work well, but rather a direct, more passive immunization that can operate without the help of a fully active immune system, is actually going to be very, very important to get out to individuals who otherwise can't do the translation process of a vaccine—from receiving an antigen or an mRNA vaccine and translating that into protection. We kind of do the work for you by building that monoclonal antibody outside of the body and then bringing it inside the body through an injection.

That's one of the areas where we think that for older individuals—individuals over 65 at high risk for COVID-19—a monoclonal really starts to shine relative to the other opportunities that individuals have for immunoprophylaxis today.

Reference

1. McCrear S. VYD2311 shows superior safety vs mRNA COVID-19 vaccine. AJMC. October 1, 2026. Accessed October 7, 2026. https://www.ajmc.com/view/vyd2311-shows-superior-safety-vs-mrna-covid-19-vaccine