Monoclonal antibodies against the spike protein alter the endogenous humoral response to SARS-CoV-2 vaccination and infection.

Autor:	Petro CD; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Hooper AT; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Peace A; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Mohammadi K; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Eagan W; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Elbashir SM; Moderna Inc., Cambridge, MA 02139, USA., DiPiazza A; Moderna Inc., Cambridge, MA 02139, USA., Makrinos D; Moderna Inc., Cambridge, MA 02139, USA., Pascal K; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Bandawane P; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Durand M; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Basu R; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Coppi A; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Wang B; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Golubov J; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Asrat S; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Ganguly S; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Koehler-Stec EM; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Wipperman MF; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Ehrlich G; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Gonzalez Ortiz AM; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Isa F; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Lewis MG; Bioqual, Rockville, MD 20850, USA., Andersen H; Bioqual, Rockville, MD 20850, USA., Musser BJ; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Torres M; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Lee WY; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Edwards D; Moderna Inc., Cambridge, MA 02139, USA., Skokos D; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Orengo J; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Sleeman M; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Norton T; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., O'Brien M; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Forleo-Neto E; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Herman GA; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Hamilton JD; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Murphy AJ; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Kyratsous CA; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA., Baum A; Regeneron Pharmaceuticals Inc., Tarrytown, NY 10591, USA.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2024 Nov 06; Vol. 16 (772), pp. eadn0396. Date of Electronic Publication: 2024 Nov 06.
DOI:	10.1126/scitranslmed.adn0396
Abstrakt:	Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein-directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti-spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2-infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection.
Databáze:	MEDLINE
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