Seroneutralization of Omicron BA.1 and BA.2 in patients receiving anti-SARS-CoV-2 monoclonal antibodies

Abstract

The SARS-CoV-2 Omicron BA.1 variant has been supplanted in many countries by the BA.2 sub-lineage. BA.2 differs from BA.1 by about 21 mutations in its spike. Human anti-spike monoclonalantibodies(mAbs)areusedforpreventionortreatmentofCOVID-19. However, the capacity of therapeutic mAbs to neutralize BA.1 and BA.2 remains poorly characterized. Here, we first compared the sensitivity of BA.1 and BA.2 to neutralization by 9 therapeutic mAbs. In contrast to BA.1, BA.2 was sensitive to Cilgavimab, partly inhibited by Imdevimab and resistant to Adintrevimab and Sotrovimab. Two combinations of mAbs, Ronapreve (Casirivimab + Imdevimab) and Evusheld (Cilgavimab + Tixagevimab), are indicated as a pre-exposure prophylaxis in immunocompromised persons at risk of severe disease. We analyzed sera from 29 such individuals, up to one month after administration of Ronapreve and/or Evusheld. After treatment, all individuals displayed elevated antibody levels in their sera and neutralized Delta with high titers. Ronapreve recipients did not neutralize BA.1 and weakly impaired BA.2. With Evusheld, neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 patients, respectively. As compared to Delta, titers were more severely decreased against BA.1 (344-fold) than BA.2 (9-fold). We further report 4 breakthrough Omicron infections among the 29 participants. Therefore, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron activity of Ronapreve, and to a lesser extent that of Evusheld, is reduced in patients sera, a phenomenon associated with decreased clinical efficacy.

Potent Human Broadly SARS-CoV-2 Neutralizing IgA and IgG Antibodies Effective Against Omicron BA.1 and BA.2

“…Omicron BA.1 contains 15 RBD-amino acid substitutions, which conferred resistance to numerous potent anti-RBD neutralizers including those in clinical use (Cameroni et al, 2022; Cao et al, 2022a; Planas et al, 2022). BA.2 has 7 amino acids differing from BA.1 in the RBD, and is also less sensitive to antibody neutralization (Bruel et al, 2022). Cv2.1169 and Cv2.3194, but not the other anti-RBD antibodies, bound well to cell-expressed and soluble BA.1 spike proteins as well as to the BA.1 RBD ( Figure 5A ).…”

“…Viruses SARS-CoV-2 BetaCoV/France/IDF0372/2020 (GISAID ID: EPIISL_406596) and D614G (hCoV-19/France/GE1973/2020; GISAID ID: EPI_ISL_414631) strains were supplied by the National Reference Centre for Respiratory Viruses (Institut Pasteur, France) (Grzelak et al, 2020;Planas et al, 2021a). α (B.1.1.7; GISAID ID: EPI_ISL_735391), β (B.1.351; GISAID ID: EPI_ISL_964916), δ (B.1.617.2; GISAID ID: EPI_ISL_2029113), ο BA.1 (GISAID ID: EPI_ISL_6794907) and BA.2 strains were provided by the Virus and Immunity Unit (Institut Pasteur) (Planas et al, 2021b(Planas et al, , 2021a(Planas et al, , 2022Bruel et al, 2022). γ variant (P.1.…”

Time to negative PCR conversion amongst high-risk patients with mild-to-moderate Omicron BA.1 and BA.2 COVID-19 treated with sotrovimab or nirmatrelvir

“…As experienced by another real-life study [ 7 ], Nirmatrelvir and Sotrovimab-based strategies were not used in the same patients. Nirmatrelvir was prescribed mainly to BA.2-infected patients, as the drug was made available under a compassionate use authorization in France on January 20 th 2022, when the BA.2 sublineage was beginning to replace the BA.1 sublineage, since lower in vitro neutralizing ability of Sotrovimab on the BA.2 sublineage was demonstrated [ 12 ]. Although Sotrovimab was associated with a low incidence of COVID-19 Omicron BA.2 progression among very high-risk outpatients, and with no emergence of mutations [ 3 ], the WHO recently made a strong recommendation against its use [ 13 ].…”

Understanding spatiotemporal symptom onset risk of Omicron BA.1, BA.2 and hamster-related Delta AY.127

“…Currently, the sub-variants of Omicron are mainly divided into five groups: BA.1, BA.2, BA.3, BA.4, and BA.5 (3,4). Of these, the BA.1 subvariant was initially the predominant of the global Omicron lineage, but the global proportion of COVID-19 cases, associated with the BA.2 variant had been increasing rapidly (5)(6)(7)(8). Hong Kong had generally well controlled the attack of all former prominent COVID-19 variants, but resultantly the people had acquired little immunity from infections.…”

“…By the identified sequences and epidemiological link of these cases, the enhanced urban-community-level weighted kernel density estimation (WKDE) model (28)(29)(30)(31) will then, be proposed to predict the spatiotemporal COVID-19 symptom onset risk of Omicron BA.1, BA.2, and Delta AY.127 in 291 Tertiary Planning Units (TPUs) of Hong Kong (Figure 1). (i) Locations with symptomatic cases resided/visited, (ii) locations with positive sewage testing results, (iii) time-varying vaccination rate and vaccination efficiency (6,(32)(33)(34)(35)(36) were incorporated to enhance the WKDE model. Based on the onset risk prediction results during the first 20 days, simulated were the early spatiotemporal spread of Omicron BA.…”