Pairing VYD2311 With mRNA COVID-19 Vaccines: Michael Mina, MD, PhD

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Results from the phase 3 LIBERTY trial (NCT07655180), which compared the safety and tolerability of a next-generation monoclonal antibody with an mRNA-based COVID-19 vaccine, revealed what Michael Mina, MD, PhD, chief medical officer and chief epidemiologist, Invivyd, called a "rare possibility of a win-win-win in the immunization space."¹

The investigational monoclonal antibody VYD2311 (Invivyd) shares the antibody backbone of Invivyd's pre-exposure prophylaxis (PrEP) treatment pemivibart (Pemgarda), which is available only under emergency use authorization for certain immunocompromised individuals. In the trial, researchers found that when VYD2311 was administered concomitantly with an mRNA-based COVID-19 vaccine, it boosted overall neutralizing antibody titers, reduced systemic adverse events (AEs) associated with the vaccine, and did not interfere with vaccine-induced neutralizing antibodies. These findings come amid declining COVID-19 vaccine uptake, which Mina, said is driven in large part by people's reluctance to tolerate vaccine-related AEs.

"The CDC and others have put out interesting data that's unsurprising to anyone who's gotten a vaccine for the most part that says that there's a lot of hesitancy that isn't borne out of a lot of what we hear in the media," he said in an interview with The American Journal of Managed Care^® (AJMC^®). "It's more about people's willingness to tolerate some of the side effects of the vaccine."

The study aimed to assess 2 things: how the tolerability of VYD2311 compared with that of an mRNA-based vaccine and whether VYD2311 interfered with the immunogenicity desired from an mRNA-based vaccine. The trial met all of its primary and secondary end points when comparing VYD2311 with Pfizer and BioNTech's mRNA-based COVID-19 vaccine, Comirnaty.

Within 6 days of dosing, 56.5% of participants receiving VYD2311 experienced a treatment-emergent AE, injection site reaction, or hypersensitivity reaction compared with 91.4% of participants receiving the vaccine (P < .0001).

"What we expected to see, we did see, which is that there were significantly reduced symptoms and side effects and tolerability issues associated with receiving a monoclonal antibody–based immunization with [VYD]2311 as opposed to getting an mRNA-based immunization," Mina said.

What surprised the researchers was the effect of giving both at once. Systemic Aes occurred in 50.0% of participants who received VYD2311 and the vaccine vs 68.1% of those who received jsut the vaccine (P = .023).

"The presence of the monoclonal antibody actually reduced the overall adverse symptoms somebody was experiencing from the vaccine," Mina said.

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