Evusheld and COVID-19 vaccination

The FDA recommends waiting 2 weeks after any COVID-19 vaccination before starting Evusheld. Currently, it is recommended COVID-19 vaccination should be delayed 90 days from the administration of monoclonal antibodies or convalescent plasma for treatment of acute illness. This is based, most likely, on the theoretical concern that the presence of antibody may impair antigen presentation to immunocytes. Although the vaccines approved prior to the last week were not protein based, these vaccines still rely on production of viral antigen, which could be neutralized by the monoclonal or passive antibody in convalescent plasma. A protein subunit vaccine was submitted for FDA approval on January 31, 2022. In my opinion, response to this vaccine may be more inhibited by the presence of pre-existing antibody (1).

I could not find specific recommendations for Evusheld (tixagevimab and cilgavimab). The half-life of this combination is prolonged with titers > 3 fold greater than neutralization titers 9 months after administration (2). The prolonged half-life is achieved by novel amino acid substitutions in the IgG1k Fc region which Fc gamma receptor and complement binding but do not affect neutralizing capability (2). The result is that this preventative anibody is administered every 6 months. If treatment with monoclonals with a 2-3 week half-life are linked with a 90 day delay in vaccination, the delay would need to be more than a year following Evusheld, if this is based on half-life.

I will add that I am skeptical that the presence of monoclonal antibody or passive antibody will significantly modify the vaccine response. This is based upon the robust vaccine response in individuals with prior COVID-19 (3). These individuals often have high titer viral antibody and yet mount a stronger response than the vaccination of naïve individuals. Admittedly a prior infection is not equivalent to monoclonal antibody administration, but I offer this as evidence that one can respond to the vaccine in the setting of pre-existing specific anti-viral antibody.

In summary, I could find no specific information concerning Evusheld and vaccination. I would prefer that the vaccination be given prior to Evusheld. Otherwise, would suggest vaccinating in the month prior to the next dose. I emphasize that the half-life of the Evusheld monoclonals means the antibody activity is still present during the month prior to the next dose of Evusheld. The effect on vaccination is unknown as best I can tell.

1. Novavax Submits Request to the U.S. FDA for Emergency Use Authorization of COVID-19 Vaccine - Jan 31, 2022
2. Loo YM, McTamney PM, Arends RH et al. doi: https://doi.org/10.1101/2021.08.30.21262666
3. Helle, François, et al. "Humoral anti-SARS-CoV-2 immune response after two doses of Comirnaty vaccine in nursing home residents by previous infection status." Vaccine (2021).

I hope this information is of help to you and your practice.

All my best.
Dennis K. Ledford, MD, FAAAAI