Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without omicron breakthrough infection

International audienceBackground: Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, which displays enhanced antibody escape properties.Methods: Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 18 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta, and Omicron BA.1, BA.2, and BA.5 variants in 300 sera and 35 nasal swabs from 27 individuals.Findings: Upon vaccination, serum Nab titers were decreased by 10-, 15-, and 25-fold for BA.1, BA.2, and BA.5, respectively, compared with D614G. We estimated that, after boosting, the duration of neutralization was markedly shortened from 11.5 months with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 5-6 months. In nasal swabs, infection, but not vaccination, triggered a strong immunoglobulin A (IgA) response and a detectable Omicron-neutralizing activity.Conclusions: BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants

Longitudinal analysis of serum neutralization of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 in patients receiving monoclonal antibodies

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Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2 in patients receiving monoclonal antibodies

International audienceThe severe acute respiratory syndrome coronavirus 2 Omicron BA.1 sublineage has been supplanted in many countries by the BA.2 sublineage. BA.2 differs from BA.1 by about 21 mutations in its spike. In this study, we first compared the sensitivity of BA.1 and BA.2 to neutralization by nine therapeutic monoclonal antibodies (mAbs). In contrast to BA.1, BA.2 was sensitive to cilgavimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab. We then analyzed sera from 29 immunocompromised individuals up to 1 month after administration of Ronapreve (casirivimab and imdevimab) and/or Evusheld (cilgavimab and tixagevimab) antibody cocktails. All treated individuals displayed elevated antibody levels in their sera, which efficiently neutralized the Delta variant. Sera from Ronapreve recipients did not neutralize BA.1 and weakly inhibited BA.2. Neutralization of BA.1 and BA.2 was detected in 19 and 29 out of 29 Evusheld recipients, respectively. As compared to the Delta variant, neutralizing titers were more markedly decreased against BA.1 (344-fold) than BA.2 (nine-fold). We further report four breakthrough Omicron infections among the 29 individuals, indicating that antibody treatment did not fully prevent infection. Collectively, BA.1 and BA.2 exhibit noticeable differences in their sensitivity to therapeutic mAbs. Anti-Omicron neutralizing activity of Ronapreve and, to a lesser extent, that of Evusheld is reduced in patients' sera

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization

International audienceThe SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose

Sotrovimab therapy elicits antiviral activities against Omicron BQ.1.1 and XBB.1.5 in sera of immunocompromised patients [letter]

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