A deep learning framework for predicting the neutralizing activity of COVID-19 therapeutics and vaccines against evolving SARS-CoV-2 variants DOI
Robert P. Matson, Işın Y. Comba, Eli Silvert

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 26, 2023

Abstract Understanding how viral variants evade neutralization is crucial for improving antibody-based treatments, especially with rapidly evolving viruses like SARS-CoV-2. Yet, conventional assays are limited in the face of rapid evolution, relying on a narrow set isolates, and falling short capturing full spectrum variants. To address this, we have developed deep learning approach to predict changes neutralizing antibody activity COVID-19 therapeutics vaccines against emerging First, trained variational autoencoder (VAE) using all 67,885 unique SARS-CoV-2 spike protein sequences from NCBI virus (up October 31, 2022) database encode into latent space. Using this VAE curated dataset 7,069 vitro assay data points NCATS OpenData Portal, neural network regression model fold 40 sequence variants, relative their ancestral strain (Wuhan-Hu-1). Our also employs Bayesian inference quantify prediction uncertainty, providing more nuanced informative estimates. validate model’s predictive capacity, assessed its performance test collected up eight months after included training (N = 980). The accurately predicted prospective dataset, an R 2 0.77. Expanding our methodology include available Portal date, current monoclonal antibodies newly identified lineages. predictions suggest that therapeutic vaccine-induced will significantly reduced newer XBB descendants, notably EG.5, FL.1.5.1, XBB.1.16. model, were able primarily attribute observed loss F456L mutation found EG.5 FL.1.5.1 sequences. Conversely, mRNA-bivalent be less susceptible recent BA.2.86 variant compared new descendants. These findings align closely research, underscoring potential shaping vaccine strategies

Language: Английский

Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86 DOI Creative Commons
Ninaad Lasrado, Ai‐ris Y. Collier, Nicole P. Hachmann

et al.

Vaccine, Journal Year: 2023, Volume and Issue: 41(47), P. 6904 - 6909

Published: Oct. 21, 2023

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show NAb titers are substantially lower to but similar slightly higher than other current circulating variants, including EG.5.1, FL.1.5.1. Moreover, against all these variants were vaccinated individuals a history of XBB.1.5 infection no infection, suggesting potential utility monovalent mRNA boosters.

Language: Английский

Citations

81
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion DOI Creative Commons
Delphine Planas, Isabelle Staropoli, Vincent Michel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolated and characterized XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF, BA.2.86.1 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicated IGROV-1 no longer Vero E6 were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhanced NAb against both BA.2.86 displayed affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Language: Английский

Citations

32
EG.5 (Eris) and BA.2.86 (Pirola) two new subvariants of SARS-CoV-2: a new face of old COVID-19 DOI

Abdolreza Esmaeilzadeh,

Fereshteh Ebrahimi, Armin Jahani Maleki

et al.

Infection, Journal Year: 2024, Volume and Issue: 52(2), P. 337 - 343

Published: Jan. 3, 2024

Language: Английский

Citations

8
SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage? DOI Creative Commons
Daniele Focosi, Pietro Giorgio Spezia, Fabrizio Maggi

et al.

Vaccines, Journal Year: 2023, Volume and Issue: 11(11), P. 1634 - 1634

Published: Oct. 25, 2023

The SARS-CoV-2 sublineage BA [...].

Language: Английский

Citations

14
Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine DOI Creative Commons
Kayvon Modjarrad, Ye Che, Wei Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 20, 2023

ABSTRACT As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains same mRNA backbone as original modified incorporation XBB.1.5-specific sequence changes encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible predominantly open one-RBD-up state, with high affinity binding human ACE-2 receptor. When administered 4 th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose primary series naïve mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together prior experience variant-adapted preclinical clinical studies, suggest is anticipated confer protective dominant ONE-SENTENCE SUMMARY The encodes immunogen elicits more potent antibody homologous other compared thus demonstrating importance annual strain

Language: Английский

Citations

14
Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine DOI Creative Commons
Kayvon Modjarrad, Ye Che, Wei Chen

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: Nov. 20, 2024

Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative original backbone, encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible, predominantly open, state, with high affinity human ACE-2 receptor. When administered as 4th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose series naive mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together real world performance suggest preclinical data predictive protective dominant

Language: Английский

Citations

5
Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay DOI Open Access
Naomi S. Coombes, Kevin R. Bewley, Yann Le Duff

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 23, 2023

Abstract New vaccines, therapeutics and immunity elicited by natural infection create evolutionary pressure on SARS-CoV-2 to evolve adapt evade vaccine-induced infection-elicited immunity. Vaccine developers thus find themselves in an “arms race” with the virus. The ongoing assessment of emerging variants remains essential as global community transitions from emergency response a long-term management plan. Here, we describe how authentic virus neutralisation assay using low passage clinical isolates has been employed monitor resistance neutralising antibodies humans experimentally infected hamsters. Sera plasma people who received three doses vaccine well those bivalent booster were assessed against variants, up including JN.1. Contemporary or recent showed substantial had ancestral but still effectively neutralised individuals (ancestral/BA.1). In our studies, however, JN.1 VOI was found be significantly more resistant ancestral/BA.1 boost. Convalescent sera hamsters that one seven (ancestral, BA.1, BA.4, BA.5.2.1, XBB.1.5, XBB.1.16, XBB.2.3) also tested here. contemporary variant, BA.2.86, XBB.1.5 XBB.1.16 it not BA.5.2.1. These data support recommendations given WHO new required should consist XBB sub-lineage antigen.

Language: Английский

Citations

9
Profiling of linear B-cell epitopes against human coronaviruses in pooled sera sampled early in the COVID-19 pandemic DOI Open Access
Emil Bach, Mustafa Ghanizada,

Nikolaj Kirkby

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Abstract Background Antibodies play a key role in the immune defence against infectious pathogens. Understanding underlying process of B cell recognition is not only fundamental interest; it supports important applications within diagnostics and therapeutics. Whereas nature conformational epitope inherently complicated, linear epitopes offer straightforward approach that potentially can be reduced to one peptide recognition. Methods Using an overlapping representing entire proteomes seven main coronaviruses known infect humans, we analysed sera pooled from eight PCR-confirmed COVID-19 convalescents pre-pandemic controls. high-density microarray platform, 13-mer peptides by 11 amino acids were situ synthesised incubated with primary serum samples, followed development secondary fluorochrome-labelled anti-IgG -IgA antibodies. Interactions detected fluorescence detection. Strong Ig interactions encompassing consecutive considered represent “high-fidelity regions” (HFRs). These mapped coronavirus using 60% homology threshold for clustering. Results We identified 333 human derived HFRs. Among these, 98 (29%) SARS-CoV-2, 144 (44%) or more four circulating common cold (CCC), 54 (16%) cross-mapped both SARS-CoV-2 CCCs. The remaining 37 (11%) either SARS-CoV MERS-CoV. Notably, was skewed towards recognising SARS-CoV-2-mapped HFRs, whereas CCC-mapped In terms absolute numbers epitopes, targets are ORF1ab protein (60%), spike (21%), nucleoprotein (15%) order; however, density order would reversed. Conclusion across coronaviruses, highlighting pan-, alpha-, beta-, SARS-CoV-2-corona-specific patterns. findings could pivotal deciphering past current exposures epidemic endemic coronavirus. Moreover, our results suggest anti-CCC antibodies may cross-react which explain highly variable outcome COVID-19. Finally, methodology used here offers rapid comprehensive high-resolution B-cell mapping, vital future studies emerging diseases.

Language: Английский

Citations

0
Protection of Omicron bivalent vaccine, previous infection, and their induced neutralizing antibodies against symptomatic infection with Omicron XBB.1.16 and EG.5.1 DOI Creative Commons
Shohei Yamamoto, Kouki Matsuda, Kenji Maeda

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 31, 2024

Abstract Background Data are limited on the protective role of Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against XBB.1.16 EG.5.1 infection. Methods We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received three or more doses COVID-19 vaccines donated blood samples June 2023 (1 month before wave). identified 206 symptomatic cases between September selected controls with 1:1 propensity-score matching. examined association vaccination, preinfection live-virus antibody titers risk Results Previous infection during BA- XBB-dominant phases was associated significantly lower dominant phase than infection-naïve 70% 100% protection, respectively, whereas vaccination showed no association. Preinfection-neutralizing were 39% (95%CI: 8–60) 28% 8–44), matched controls. Neutralizing activity EG.5.1. somewhat detectable sera individuals but barely those vaccine. Conclusions In era when XBB vaccine unavailable, did not confer protection The afforded these variants. Main points

Language: Английский

Citations

0
In Silico Evaluation of Ten Monoclonal Antibodies Neutralization Power of SARS-CoV-2 Variants EG.5, BA.2.86 and JN.1 DOI Open Access
Dana Ashoor

Published: Aug. 19, 2024

The current globally dominant SARS-CoV-2 variants are showing immune escape and reduced susceptibility to antiviral drugs. Therefore, agencies responsible for drug evaluation regulation such as the FDA EMA revising their emergency authorization use of several COVID-19 neutralizing antibodies. These MAbs proved be unlikely effective against new especially Omicron descendants pharmaceutical companies pursuing development more potent To address this issue, we used In Silico method previously developed assess 10 anti-SARS-CoV-2 antibodies propensity neutralize Omicron’s subvariants EG.5, BA.2.86 JN.1, based on comparative binding affinity 3D generated models previous experimental clinical observations. Nine these were once granted authorization, one is currently under investigation. results showed that antibody a marked increase energy EG.5 compared two significant with Pirola (BA.2.86) JN.1. This data indicates variant escapes neutralization most available therapeutic NAbs. Furthermore, potential combination could treatment countermeasure or novel variants.

Language: Английский

Citations

0