tetano
Editor, Senior Moderator
PLoS One
. 2025 Jun 18;20(6):e0325561.
doi: 10.1371/journal.pone.0325561. eCollection 2025. Long-term anti-SARS-CoV-2 antibody trajectories after neutralizing monoclonal antibody treatment
Elizabeth S Munroe[SUP] 1 [/SUP], Greg A Grandits[SUP] 2 [/SUP], Robert C Hyzy[SUP] 1 [/SUP], Hallie C Prescott[SUP] 1 3 [/SUP], Thomas W Barrett[SUP] 4 [/SUP], Robin L Dewar[SUP] 5 [/SUP], Nicole Engen[SUP] 2 [/SUP], Anna L Goodman[SUP] 6 7 [/SUP], Timothy J Hatlen[SUP] 8 [/SUP], Helene Highbarger[SUP] 5 [/SUP], Thomas L Holland[SUP] 9 10 [/SUP], Gareth Hughes[SUP] 6 [/SUP], Tomas O Jensen[SUP] 11 [/SUP], Muhammad A Khan[SUP] 5 [/SUP], Ioannis Kalomenidis[SUP] 12 [/SUP], Nayon Kang[SUP] 13 [/SUP], Sylvain Laverdure[SUP] 14 [/SUP], Prasad Manian[SUP] 15 [/SUP], Vidya Menon[SUP] 16 [/SUP], Ravi Patel[SUP] 17 [/SUP], Srikanth Ramachandruni[SUP] 18 [/SUP], Tauseef Rehman[SUP] 19 [/SUP], Kathryn Shaw-Saliba[SUP] 13 [/SUP], Birgit Thorup Røge[SUP] 20 [/SUP], David M Vock[SUP] 2 [/SUP], Amy C Weintrob[SUP] 21 [/SUP], Barnaby E Young[SUP] 22 [/SUP], Anne P Frosch[SUP] 23 [/SUP]; STRIVE Network and Therapeutics for Inpatients with COVID-19 (TICO) study groups
Affiliations
Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.
Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements of the spike protein response reflect both the therapeutic and endogenous immune response. Anti-nucleocapsid levels reflect only the endogenous immune response. Data are summarized as mean differences in percent binding inhibition (anti-spike) and signal-to-cutoff (S/C) ratio (anti-nucleocapsid). Linear mixed effects models were fit to compare the longitudinal trajectory between treatment and placebo groups.
Results: Of 2,254 participants in the ACTIV-3/TICO trials modified intention-to-treat population, 2,149 (95.3%) had antibody measures at baseline and at least 1 follow-up day (day 1, 3, or 5) and were included in this analysis. Antibody measures were available for 1,556 (72.4%) participants at day 28 and 1,429 (66.5%) participants at day 90. In participants who received nMAbs, anti-spike neutralization activity was higher at day 28 (mean difference in percent binding inhibition: 7.1% [95%CI: 5.3, 8.9], p < 0.001) and day 90 (mean difference in percent binding inhibition: 7.2% [95% CI: 5.4, 9.0], p < 0.001). Anti-nucleocapsid response was similar at day 28 (mean difference in S/C ratio: 0.02 [95%CI: -0.11, 0.15], p = 0.75) and day 90 (mean difference in S/C ratio: 0.08 [95% CI: -0.05, 0.21], p = 0.22). Similar patterns were observed in all trials.
Conclusions: In patients hospitalized with COVID-19, treatment with nMAbs did not decrease long-term anti-nucleocapsid response compared to placebo, suggesting neutralizing therapies do not suppress the endogenous humoral immune response in this population.
. 2025 Jun 18;20(6):e0325561.
doi: 10.1371/journal.pone.0325561. eCollection 2025. Long-term anti-SARS-CoV-2 antibody trajectories after neutralizing monoclonal antibody treatment
Elizabeth S Munroe[SUP] 1 [/SUP], Greg A Grandits[SUP] 2 [/SUP], Robert C Hyzy[SUP] 1 [/SUP], Hallie C Prescott[SUP] 1 3 [/SUP], Thomas W Barrett[SUP] 4 [/SUP], Robin L Dewar[SUP] 5 [/SUP], Nicole Engen[SUP] 2 [/SUP], Anna L Goodman[SUP] 6 7 [/SUP], Timothy J Hatlen[SUP] 8 [/SUP], Helene Highbarger[SUP] 5 [/SUP], Thomas L Holland[SUP] 9 10 [/SUP], Gareth Hughes[SUP] 6 [/SUP], Tomas O Jensen[SUP] 11 [/SUP], Muhammad A Khan[SUP] 5 [/SUP], Ioannis Kalomenidis[SUP] 12 [/SUP], Nayon Kang[SUP] 13 [/SUP], Sylvain Laverdure[SUP] 14 [/SUP], Prasad Manian[SUP] 15 [/SUP], Vidya Menon[SUP] 16 [/SUP], Ravi Patel[SUP] 17 [/SUP], Srikanth Ramachandruni[SUP] 18 [/SUP], Tauseef Rehman[SUP] 19 [/SUP], Kathryn Shaw-Saliba[SUP] 13 [/SUP], Birgit Thorup Røge[SUP] 20 [/SUP], David M Vock[SUP] 2 [/SUP], Amy C Weintrob[SUP] 21 [/SUP], Barnaby E Young[SUP] 22 [/SUP], Anne P Frosch[SUP] 23 [/SUP]; STRIVE Network and Therapeutics for Inpatients with COVID-19 (TICO) study groups
Affiliations
- PMID: 40531973
- PMCID: PMC12176123
- DOI: 10.1371/journal.pone.0325561
Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.
Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements of the spike protein response reflect both the therapeutic and endogenous immune response. Anti-nucleocapsid levels reflect only the endogenous immune response. Data are summarized as mean differences in percent binding inhibition (anti-spike) and signal-to-cutoff (S/C) ratio (anti-nucleocapsid). Linear mixed effects models were fit to compare the longitudinal trajectory between treatment and placebo groups.
Results: Of 2,254 participants in the ACTIV-3/TICO trials modified intention-to-treat population, 2,149 (95.3%) had antibody measures at baseline and at least 1 follow-up day (day 1, 3, or 5) and were included in this analysis. Antibody measures were available for 1,556 (72.4%) participants at day 28 and 1,429 (66.5%) participants at day 90. In participants who received nMAbs, anti-spike neutralization activity was higher at day 28 (mean difference in percent binding inhibition: 7.1% [95%CI: 5.3, 8.9], p < 0.001) and day 90 (mean difference in percent binding inhibition: 7.2% [95% CI: 5.4, 9.0], p < 0.001). Anti-nucleocapsid response was similar at day 28 (mean difference in S/C ratio: 0.02 [95%CI: -0.11, 0.15], p = 0.75) and day 90 (mean difference in S/C ratio: 0.08 [95% CI: -0.05, 0.21], p = 0.22). Similar patterns were observed in all trials.
Conclusions: In patients hospitalized with COVID-19, treatment with nMAbs did not decrease long-term anti-nucleocapsid response compared to placebo, suggesting neutralizing therapies do not suppress the endogenous humoral immune response in this population.