Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography (preprint)

Since emergence of the initial SARS-CoV-2 omicron BA.1, BA.2 and BA.5 variants, omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5 omicron. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/23289412v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@16819e7org.highwire.dtl.DTLVardef@17c9bc6org.highwire.dtl.DTLVardef@1d6f349org.highwire.dtl.DTLVardef@fe6ec7_HPS_FORMAT_FIGEXP M_FIG C_FIG

BA.2 omicron differs immunologically from both BA.1 omicron and pre-omicron variants (preprint)

Background: Several studies have shown that SARS-CoV-2 BA.1 omicron is an immune escape variant and current vaccines and infection with pre-omicron variants provide limited protection against BA.1. Meanwhile, however, omicron BA.2 has become the dominant variant in many countries and has replaced BA.1. As BA.2 has several mutations especially in the receptor binding and the N terminal domain compared to BA.1, we analyzed whether BA.2 shows further immune escape relative to BA.1. Methods: We characterized neutralization profiles against the new BA.2 omicron variant in plasma samples from a variety of individuals with different numbers of exposures to infection/vaccination, including samples from previously virus-naive, BA.2 omicron-infected individuals. To illustrate antigenic differences of the two omicron sub-variants and pre-omicron variants we performed antigenic cartography and generated antibody landscapes. Results: Unvaccinated individuals after a single exposure to BA.2 had limited cross-neutralizing antibodies to pre-omicron variants and to BA.1. Consequently, our antigenic map, which included all Variants of Concern and both BA.1 and BA.2 omicron sub-variants, showed that both omicron sub-variants are distinct to pre-omicron variants, but that the two omicron variant are also antigenically distinct from each other. The antibody landscapes illustrate that cross-neutralizing antibodies against the whole antigenic space, as described in our maps, are generated only after three or more exposures to antigenically close variants but also after two exposures to antigenically distinct variants. Conclusions: Here, we describe the antigenic space inhabited by the relevant SARS-CoV-2 variants, the understanding of which will have important implications for further vaccine strain adaptations.

Immune response to 2-dose BNT162b2 vaccination and risk of SARS-CoV-2 breakthrough infection: The Shieldvacc-2 study (preprint)

It is uncertain to which extent antibody and T-cell responses after vaccination against SARS-CoV-2 are associated with reduced risk of breakthrough infection and whether their measurement enhances risk prediction. We conducted a phase-4 open-label clinical trial in the pre-omicron era, enrolling 2,760 individuals aged [≥]16 years 35{+/-}8 days after having received the second dose of BNT162b2 (baseline 15-21 May 2021). Over a median 5.9-month of follow-up, we identified incident SARS-CoV-2 breakthrough infections using weekly antigen tests, a confirmatory PCR test, and/or serological evidence for incident infection. We quantified relative risks adjusted for age, sex, and prior SARS-CoV-2 infection for different immunological parameters and assessed improvements in risk discrimination. In contrast to the T-cell response, higher plasma levels of binding antibodies and antibodies in a surrogate neutralization assay were associated with reduced risk of breakthrough infection. Furthermore, assessment of anti-spike IgG levels enhanced prediction of breakthrough infection and may therefore be a suitable measurable correlate of protection in practice.

Follow-up study in the ski-resort Ischgl: Antibody and T cell responses to SARS-CoV-2 persisted for up to 8 months after infection and transmission of virus was low even during the second infection wave in Austria (preprint)

Background: In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a cross-sectional study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April. To answer the question of how long immunity persists and what effect this high-level immunity had on virus transmission, we performed a follow-up study in early November, 2020. Methods: Of the 1259 adults that participated in the baseline study, 801 could be included in the follow-up. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 infections in Ischgl was compared to the incidence in similar municipalities in Tyrol throughout 2020. Findings: For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9 - 54.9) to 45.4% (95% CI 42.0 - 49.0). Median antibody concentrations dropped considerably but antibody avidity increased. T cell responses were analysed in 93 cases, including all 4 formerly seropositive cases that had lost antibodies in all assays, three of which still had detectable T cell memory. In addition, the incidence in the second COVID-19 wave that hit Austria in November 2020, was significantly lower in Ischgl than in comparable municipalities in Tyrol or the rest of Austria. Interpretation: This study has important implications as it shows that although antibodies to SARS-CoV-2 declined, T and B cell memory can be detected for up to 8 months. Complemented by infection prevention measures a level of around 40-45% immunity in Ischgl significantly reduced local virus transmission during the second wave in Austria in November 2020. Funding: Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.

Prevalence of RT-PCR-detected SARS-CoV-2 infection at schools: First results from the Austrian School-SARS-CoV-2 Study (preprint)

BackgroundThe role of schools in the SARS-CoV-2 pandemic is much debated. We aimed to quantify reliably the prevalence of SARS-CoV-2 infections at schools detected with reverse-transcription quantitative polymerase-chain-reaction (RT-qPCR). MethodsThis nationwide prospective cohort study monitors a representative sample of pupils (grade 1-8) and teachers at Austrian schools throughout the school year 2020/2021. We repeatedly test participants for SARS-CoV-2 infection using a gargling solution and RT-qPCR. We herein report on the first two rounds of examinations. We used mixed-effect logistic regression to estimate odds ratios and robust 95% confidence intervals (95% CI). FindingsWe analysed data on 10734 participants from 245 schools (9465 pupils, 1269 teachers). Prevalence of SARS-CoV-2 infection increased from 0.39% at round 1 (95% CI 0.28-0{middle dot}55%, 29 September-22 October 2020) to 1{middle dot}39% at round 2 (95% CI 1{middle dot}04-1{middle dot}85%, 10-16 November). Odds ratios for SARS-CoV-2 infection were 2{middle dot}26 (95% CI 1{middle dot}25-4{middle dot}12, P=0{middle dot}007) in regions with >500 vs. [≤]500 inhabitants/km2, 1{middle dot}67 (95% CI 1{middle dot}42-1{middle dot}97, P<0{middle dot}001) per two-fold higher regional 7-day incidence, and 2{middle dot}78 (95% CI 1{middle dot}73-4{middle dot}48, P<0{middle dot}001) in pupils at schools with high/very high vs. low/moderate social deprivation. Associations of community incidence and social deprivation persisted in a multivariable adjusted model. Prevalence did not differ by average number of pupils per class nor between age groups, sexes, pupils vs. teachers, or primary (grade 1-4) vs. secondary schools (grade 5-8). InterpretationThis monitoring study in Austrian schools revealed SARS-CoV-2 infection in 0{middle dot}39%-1{middle dot}39% of participants and identified associations of regional community incidence and social deprivation with higher prevalence. FundingBMBWF Austria.

High SARS-CoV-2 Seroprevalence in Children and Adults in the Austrian Ski Resort Ischgl (preprint)

Background: Early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. Methods: Between April 21 and 27, a cross-sectional epidemiologic study targeting the full population of Ischgl (n= 1867), of which 79% could be included (n=1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission. Findings: The seroprevalence was 42.4% (95% CI 39.8-44.7). Individuals under 18 showed a significantly lower seroprevalence of 27.1% (95% CI 21.3-33.6) than adults (45%; 95% CI 42.2-47.7; OR of 0.455, 95% CI 0.356-0.682, p<0.001). Of the seropositive individuals, 83.7% had not been diagnosed to have had SARS-CoV-2 infection previously. The clinical course was generally mild. Over the previous two months, two COVID-19-related deaths had been recorded, corresponding to an infection fatality rate (IFR) of 0.25% (95% CI 0.03-0.91). Only 8 (0.5 %) individuals were newly diagnosed to be infected with SARS-CoV-2 during this study. Interpretation: Ischgl was hit early and hard by SARS-CoV-2 leading to a high local seroprevalence of 42.4%, which was lower in individuals below the age of 18 than in adults. Mathematical modeling suggests that a drastic decline of newly infected individuals in Ischgl by the end of April occured due to the dual impact from the non-pharmacological interventions (NPIs) and a significant immunization of the Ischgl population. Funding: Helmholtz Association, European Union's Horizon 2020 research and innovation program, German Research Foundation (DFG), state Tyrol.