ABSTRACT
Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. As exposure histories for human sera become more and more complex, animal sera may provide an alternative for antigenic characterization of new variants. To bridge data obtained from animal sera with human sera, we here analyzed neutralizing antibody titers in human and hamster first infection sera in a highly controlled setting using the same live-virus neutralization assay performed in one laboratory. Using a Bayesian framework, we found that titer fold changes in hamster sera corresponded well to human sera and that hamster sera generally exhibited higher reactivity. Our results indicate that sera from infected hamsters are a good surrogate for the antigenic characterization of new variants.
ABSTRACT
The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.
ABSTRACT
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
ABSTRACT
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.
ABSTRACT
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.
Subject(s)
COVID-19 , Breakthrough PainABSTRACT
Recently, the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been described as immune escape variant. Here, we analyzed samples from BA.1 (Omicron) convalescent patients with different constellations of prior SARS-CoV-2 immunity regarding vaccination and previous infection with a non-Omicron variant and determined titers of neutralizing antibodies against different SARS-CoV-2 variants (D614G, Alpha, Beta, Delta, Gamma, Omicron). We found high neutralizing antibody titers against all variants for vaccinated individuals after BA.1 breakthrough infection or for individuals after infection with a pre-omicron variant followed by BA.1 infection. In contrast, samples from naive unvaccinated individuals after BA.1 infection mainly contained neutralizing antibodies against BA.1 but only occasionally against the other variants.
Subject(s)
Coronavirus Infections , Breakthrough PainABSTRACT
Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has been described. Here, we analyze titers of neutralizing antibodies of sera from convalescent or vaccinated individuals against the new B.1.1.529 variant and compared them with titers against other Variants of Concern (B.1.1.7, B.1.351, B.1617.2) using replication competent SARS-CoV-2 variants. We found that sera from vaccinated individuals neutralized the B.1.1.529 variant to a much lesser extent than any other variant analyzed. Neutralization capacity against B.1.1.529 was maintained best against sera from super immune individuals (infected and vaccinated or vaccinated and infected).
Subject(s)
Coronavirus Infections , InfectionsABSTRACT
We studied the real-life effect of an unprecedented rapid mass vaccination campaign. Following a large outbreak of B.1.351 and B.1.1.7/E484K in the district of Schwaz/Austria, 100,000 BNT162b2 doses were procured to mass vaccinate the entire adult population (16+) of the district between the 11th and 16th of March 2021. This made the district the first widely inoculated region in Europe. We examined the effect of this unique campaign on the number of infections including VoCs, hospital and intensive care unit (ICU) admissions. We compared Schwaz with (i) a control group of highly similar districts, and (ii) with populations residing in municipalities along the border of Schwaz which were just excluded from the campaign. We find large and significant decreases for all outcomes after the campaign, including VoCs cases. The reduction relative to the control regions was largest for younger age cohorts, which were mostly non-vaccinated in the rest of the country due to the age-gradient in the national vaccination plan. Our results demonstrate that rapid population-wide mass vaccination can be an effective tool to curb overall infections as well as VoCs.
ABSTRACT
Background: In recent months numerous health care professional acquired COVID-19 at the workplace resulting in significant shortages in medical and nursing staff. We investigated how prior COVID-19 affects SARS-CoV-2 vaccination and how such knowledge could facilitate frugal vaccination strategies.Methods: In a cohort of 41 healthcare professionals with (n=14) and without (n=27) previous SARS-CoV-2 infection, we assessed the immune status before, during and after vaccination with BNT162b2. The humoral immune response was assessed by receptor binding domain ELISA and different SARS-CoV-2 neutralisation assays using wildtype and pseudo-typed viruses. T cell immunity against SARS-CoV-2 surface and nucleocapsid peptides were studied using interferon g release assays and intracellular flow cytometry. Vaccine-related side effects were captured. Findings: Prior COVID-19 resulted in improved vaccine responses both in the B and T cell compartment. In vaccine recipients with prior COVID-19, the first vaccine dose induced high antibody concentrations comparable to seronegative vaccine recipients after two injections. This translated into more efficient neutralisation of virus particles, even more pronounced than expected from the RBD ELISA results. Furthermore, T cell responses were stronger in convalescents and particularly strong against the SARS-CoV-2 nucleocapsid protein.Interpretation: Herein, we corroborate recent findings suggesting that in convalescents a single vaccine dose may be sufficient to boost adequate protection against SARS-CoV-2. New spike mutated virus variants render the highly conserved nucleocapsid protein – eliciting strong SARS-CoV-2 specific T cell immunity – an interesting additional vaccine target.Funding: Christian Doppler Research Association, Johannes Kepler University LinzDeclaration of Interests: TRK and MF are employees of Baxter AG, Vienna, Austria, now part of the Takeda group of companies and have Takeda stock interest. All other authors declare no competing interests.Ethics Approval Statement: This study was approved by the ethics committee of the Johannes Kepler University Linz (EC-No. 1322/2020) and informed consent was obtained from all study subjects.
Subject(s)
COVID-19ABSTRACT
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.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
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.