Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments

Gupta, Akshita; Konnova, Angelina; Smet, Mathias; Berkell, Matilda; Savoldi, Alessia; Morra, Matteo; averbeke, Vincent Van; Winter, Fien De; Peserico, Denise; Danese, Elisa; Hotterbeekx, An; Righi, Elda; Nardo, Pasquale De; Tacconelli, Evelina; Kumar, Surbhi Malhotra; Singh, Samir Kumar

doi:10.1101/2022.09.20.22280135

Cited by 2 publications

(1 citation statement)

References 68 publications

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“…Most of them were raised against the original Wuhan-type virus and see their neutralization potential abrogated or reduced against variants. Moreover, mAbs may favor the emergence of SARS-CoV-2-resistant variants in immunocompromised patients (7). Approved anti-SARS-CoV-2 mAbs are no longer recommended since the end of 2022 because they are unlikely to be effective against emerging strains of SARS-CoV-2 (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19

Poulakou,

Royer,

Evgeniev

et al. 2024

Front. Immunol.

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IntroductionXAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2 with high neutralizing activity. The safety and clinical efficacy of XAV-19 were investigated in patients with mild to moderate COVID-19.MethodsThis phase II/III, multicentric, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in patients with a seven-point WHO score of 2 to 4 at randomization, i.e., inpatients with COVID-19 requiring or not requiring low-flow oxygen therapy, and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Adult patients presenting in specialized or emergency units with confirmed COVID-19 and giving their consent to participate in the study were randomized to receive 150 mg of XAV-19 or placebo. The primary endpoint was the proportion of patients with aggravation within 8 days after treatment, defined as a worsening of the seven-point WHO score of at least one point between day 8 and day 1 (inclusion). The neutralization activity of XAV-19 against variants circulating during the trial was tested in parallel.ResultsFrom March 2021 to October 2022, 279 patients received either XAV-19 (N = 140) or placebo (N = 139). A slow enrollment and a low rate of events forced the termination of the premature trial. XAV-19 was well tolerated. Underpowered statistics did not allow the detection of any difference in the primary endpoint between the two groups or in stratified groups. Interestingly, analysis of the time to improvement (secondary endpoint) showed that XAV-19 significantly accelerated the recovery for patients with a WHO score of 2 or 3 (median at 7 days vs. 14 days, p = 0.0159), and even more for patients with a WHO score of 2 (4 days vs. 14 days, p = 0.0003). The neutralizing activity against Omicron and BA.2, BA.2.12.1, BA.4/5, and BQ.1.1 subvariants was shown.DiscussionIn this randomized placebo- controlled trial with premature termination, reduction of aggravation by XAV-19 at day 8 in patients with COVID-19 was not detectable. However, a significant reduction of the time to improvement for patients not requiring oxygen was observed. XAV-19 maintained a neutralizing activity against SARS-CoV-2 variants. Altogether, these data support a possible therapeutic interest for patients with mild to moderate COVID-19 requiring anti-SARS-CoV-2 neutralizing antibodies.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT04928430; https://www.clinicaltrialsregister.eu/about.html (EudraCT), identifier 2020-005979-12.

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Section: Introductionmentioning

confidence: 99%

Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19

Poulakou,

Royer,

Evgeniev

et al. 2024

Front. Immunol.

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IL-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV (PLWH)

Gupta,

Righi,

Konnova

et al. 2024

Preprint

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People living with HIV (PLWH) despite having appreciable depletion of CD4+ T-cell show a good SARS-CoV-2 vaccination response. The underlying mechanism(s) are currently not understood. We studied serological and polyfunctional T-cell responses in PLWH receiving anti-retroviral therapy stratified on CD4+ counts as PLWH-high (CD4 ≥500 cells/μL) and PLWH-low (<500 cells/μL). Responses were assessed longitudinally before the first vaccination (T0), 1-month after the first dose (T1), and 3-months (T2), and 6-months (T3) after the second dose. Expectedly, both PLWH-high and -low groups developed similar serological responses after T2, which were also non-significantly different to age and vaccination-matched HIV-negative controls at T3. The IgG titers were also protective showing a good correlation with ACE2-neutralizations (R=0.628, P=0.005). While no difference at T3 was observed between PLWH and controls in activated CD4+CD154+ and CD4+ memory T-cells, spike-specific CD4+ polyfunctional cytokine expression analysis showed that PLWH preferentially express IL-2 (P<0.001) and controls, IFN-γ (P=0.017). CD4+ T-cell counts negatively correlated with IL-2-expressing CD4+ T-cells including CD4+ memory T-cells (Spearman ρ: -0.85 and -0.80, respectively; P<0.001). Our results suggest that the durable serological and CD4+ T-cell responses developing in vaccinated PLWH are associated with IL-2-mediated CD4+ T-cell activation that likely compensates for CD4+ T-cell depletion in PLWH.

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Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments

Cited by 2 publications

References 68 publications

Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19

Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19

IL-2-mediated CD4 T-cell activation correlates highly with effective serological and T-cell responses to SARS-CoV-2 vaccination in people living with HIV (PLWH)

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