{ "abstract": "Background The impact of anti–SARS-CoV-2 monoclonal antibodies (mAbs) on adaptive immunity remain unclear, particularly regarding optimal timing for post-infection revaccination. We evaluated the longitudinal humoral and cellular immune responses after mAb therapy and compared two revaccination strategies.Methods We enrolled patients treated early with mAbs (sotrovimab or tixagevimab/cilgavimab) for mild-to-moderate SARS-CoV-2 infection. Four months after mAb administration, participants were randomised (1:1, open-label) to receive immediate vaccination (arm 1) or not (arm 2). Anti- Spike protein (anti-S) IgG, anti-nucleocapsid (anti-N) IgG, neutralising antibodies (nAbs) against XBB.1.16 and JN.1, were measured at baseline (BL) and at 1, 4, 6, 9, and 12 months, while T-cell responses to Spike and nucleocapsid peptides at BL, 1, 4 and 12 months. The primary outcome was the magnitude and durability of immune responses between groups over time. Groups were compared using t-test or Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables. Immune responses over time are shown as boxplots.Results Sixty-four patients were included (mean age 67±12 years; 47% male). BL characteristics were comparable between groups, except for prior vaccine doses (p=0.018) ( table 1). At BL, anti-S IgG, anti-N IgG, nAbs, and Spike- and nucleocapsid-specific T-cell responses were similar between arms. At randomisation, only the median value of anti-N IgG showed differences between arm 1 vs arm 2 (2.48 vs 1.55 log2S/CO; p=0.04). At month 6 (2 months post-vaccination), anti-S and anti-N IgG were significantly higher in the vaccinated versus not (13.44 vs 12.03 log2BAU/mL; p<0.001 and 2.33 vs 1.20 log2S/CO; p=0.02). NAbs titers were statistically higher for JN.1 in arm 1 (5.32 vs 4.32 log2reciprocal serum dilution; p=0.023), while similar for XBB.1.16 (6.32 vs 5.32 log2reciprocal serum dilution; p=0.66). By month 9, differences attenuated: anti-S IgG remained statistically higher in the vaccinated (12.02 vs 11.48 log2BAU/mL; p=0.034), with a trend for anti-N IgG (1.23 vs -0.29 log2S/CO; p=0.08) and comparable nAb titers levels. By 12 months, anti-Spike IgG median levels were fully comparable between groups (11.60 vs 11.59 log2BAU/mL; p=0.4). nAbs titers were similarly distributed for JN.1 (3.32 vs 3.32 log2reciprocal serum dilution; p>0.9) and XBB.1.16 (4.32 vs 4.82 log2reciprocal serum dilution; p>0.9). Spike- and nucleocapsid-specific T-cell responses were comparable, revealing a measurable response in both arms over time (figure 1).Conclusions In mAb-treated patients with mild-to-moderate SARS-CoV-2 infection, vaccination after 4 months elicited a transient rise in anti-S IgG and neutralising activity, but this advantage progressively waned, and by 12 months, immune response was comparable between vaccinated and unvaccinated participants. These findings suggest a limited benefit of early vaccination in this setting.Abstract SC18 Figure 1Humoral and cellular immune responses in patients with acute SARS-CoV-2 infection treated early with monoclonal antibodies, stratified according to vaccination: Arm 1: vaccinated 4 months after SARS-CoV-2 infection and mAb treatment; Arm 2: no vaccination received. A) Anti-Spike IgG antibodies; B) Anti-Nucleocapsid IgG antibodies; C) Neutralizing antibody titer - XBB.1.16; D) Neutralizing antibody titer-JN.1;E) Spike-specificT-cell response; F) Nucleocapsid-specific T-cell response. All variables were expressed base-2 logarithmAbstract SC18 Table 1Characteristics of the study population", "authors": [ { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "M Camici" }, { "affiliations": [ "Laboratory of Virology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "S Meschi" }, { "affiliations": [ "Laboratory of Immunology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "E Cimini" }, { "affiliations": [ "Epidemiology Unit, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "A Caioli" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "J Paulicelli" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "A Oliva" }, { "affiliations": [ "Laboratory of Virology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "M De Vito" }, { "affiliations": [ "Laboratory of Immunology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "S Gili" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "MM Plazzi" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "G Micheli" }, { "affiliations": [ "Laboratory of Virology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "D Mariotti" }, { "affiliations": [ "Laboratory of Virology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "G Matusali" }, { "affiliations": [ "Laboratory of Immunology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "F Cristofanelli" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "M Fusto" }, { "affiliations": [ "Scientific Direction, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "E Girardi" }, { "affiliations": [ "Laboratory of Virology, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "F Maggi" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy", "Health Direction, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "A Antinori" }, { "affiliations": [ "Clinical Department, INMI Lazzaro Spallanzani IRCCS, Rome, Italy" ], "name": "V Mazzotta" } ], "title": "SC18 Temporal kinetics of humoral and cellular immunity after monoclonal antibody treatment for SARS-CoV-2 and impact of vaccination timing: RENOIR study", "uid": "79235dc3-4800-5ff9-9c74-71a6b75d9b60" }