Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

Cell, Journal Year: 2022, Volume and Issue: 185(13), P. 2265 - 2278.e14

Published: April 27, 2022

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed protein subunit vaccine ZF2001 based on dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, a chimeric RBD-dimer approach to adapt variants. A prototype-Beta was first designed resistant Beta variant. Compared with its homotypic forms, elicited broader sera neutralization and conferred better protection in mice. The further verified macaques. This generalized develop Delta-Omicron currently prevalent Again, against either Delta or Omicron is applicable rapid updating immunogens, our data supported use variant-adapted multivalent circulating emerging

Language: Английский

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Efficacy of SARS-CoV-2 vaccines and the dose–response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials

The Lancet Microbe, Journal Year: 2023, Volume and Issue: 4(4), P. e236 - e246

Published: Feb. 28, 2023

Summary

Background

The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity data individual trials. How well antibody concentrations can predict also uncertain. We aimed assess these infections different severities dose–response relationship between efficacy.

Methods

did a systematic review meta-analysis randomised controlled trials (RCTs). searched PubMed, Embase, Scopus, Web Science, Cochrane Library, WHO, bioRxiv, medRxiv for papers published Jan 1, 2020 Sep 12, 2022. RCTs on were eligible. Risk bias was assessed using tool. A frequentist, random-effects model used combine common outcomes (ie, symptomatic asymptomatic infections) Bayesian rare hospital admission, infection, death). Potential sources heterogeneity investigated. relationships neutralising, spike-specific IgG receptor binding domain-specific titres with examined by meta-regression. This registered PROSPERO, CRD42021287238.

Findings

28 (n=286 915 vaccination groups n=233 236 placebo groups; median follow-up 1–6 months after last vaccination) across 32 publications included this review. combined full 44·5% (95% CI 27·8–57·4) infections, 76·5% (69·8–81·7) 95·4% credible interval 88·0–98·7) hospitalisation, 90·8% (85·5–95·1) 85·8% (68·7–94·6) death. There against but insufficient evidence suggest whether could differ according type vaccine, age vaccinated individual, between-dose (p>0·05 all). Vaccine infection waned over time vaccination, an average decrease 13·6% 5·5–22·3; p=0·0007) per month be enhanced booster. found significant non-linear each (p<0·0001 all), there remained considerable efficacy, which cannot explained concentrations. risk low most studies.

Interpretation

higher than milder infection. wanes Higher are associated estimates precise predictions difficult large unexplained heterogeneity. These findings provide important knowledge base interpretation application future studies issues.

Funding

Shenzhen Science Technology Programs.

Language: Английский

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SARS-CoV-2 Vaccines, Vaccine Development Technologies, and Significant Efforts in Vaccine Development during the Pandemic: The Lessons Learned Might Help to Fight against the Next Pandemic

Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 682 - 682

Published: March 17, 2023

We are currently approaching three years since the beginning of coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 has caused extensive disruptions in everyday life, public health, and global economy. Thus far, vaccine worked better than expected against virus. During pandemic, we experienced several things, such as virus its pathogenesis, clinical manifestations, treatments; emerging variants; different vaccines; development processes. This review describes how each been developed approved with help modern technology. also discuss critical milestones during process. Several lessons were learned from countries two research, development, trials, vaccination. The process will to fight next

Language: Английский

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Accelerating the prediction and discovery of peptide hydrogels with human-in-the-loop

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 30, 2023

Abstract The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust design (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides evaluate hydrogel-forming ability, then employ learning-experiment iterative loops to improve accuracy gelation prediction. construct score function coupling aggregation propensity, hydrophobicity, corrector C g , generate 8,000-sequence library, within which success rate predicting formation reaches 87.1%. Notably, de novo-designed peptide selected from this boosts immune response receptor binding domain SARS-CoV-2 in mice model. Our taps into potential hydrogelator significantly expands scope

Language: Английский

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An overview of the vaccine platforms to combat COVID-19 with a focus on the subunit vaccines

Progress in Biophysics and Molecular Biology, Journal Year: 2023, Volume and Issue: 178, P. 32 - 49

Published: Feb. 20, 2023

Language: Английский

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Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 10, 2023

Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS‐CoV‐2), has devastating impacts on the public health and economy. Rapid viral antigenic evolution led to continual generation new variants. Of special note is recently expanding Omicron subvariants that are capable immune evasion from most existing neutralizing antibodies (nAbs). This posed challenges for prevention treatment COVID-19. Therefore, exploring broad-spectrum antiviral agents combat emerging variants imperative. In sharp contrast massive accumulation mutations within SARS-CoV-2 receptor-binding domain (RBD), S2 fusion subunit remained highly conserved among Hence, S2-based therapeutics may provide effective cross-protection against Here, we summarize developed inhibitors (e.g., nAbs, peptides, proteins, small-molecule compounds) candidate vaccines targeting elements in subunit. main focus includes all targetable elements, namely, peptide, stem helix, heptad repeats 1 (HR1-HR2) bundle. Moreover, a detailed summary characteristics action-mechanisms each class cross-reactive inhibitors, which should guide promote future design coronaviruses.

Language: Английский

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Immune imprinting and next-generation coronavirus vaccines

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(11), P. 1971 - 1985

Published: Nov. 6, 2023

Language: Английский

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Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(8), P. 1216 - 1223

Published: May 6, 2024

Abstract Defending against future pandemics requires vaccine platforms that protect across a range of related pathogens. Nanoscale patterning can be used to address this issue. Here, we produce quartets linked receptor-binding domains (RBDs) from panel SARS-like betacoronaviruses, coupled computationally designed nanocage through SpyTag/SpyCatcher links. These Quartet Nanocages, possessing branched morphology, induce high level neutralizing antibodies several different coronaviruses, including viruses not represented in the vaccine. Equivalent antibody responses are raised RBDs close or at tips nanoparticle’s branches. In animals primed with SARS-CoV-2 Spike, boost immunizations Nanocages increase strength and breadth an otherwise narrow immune response. A Nanocage Omicron XBB.1.5 ‘Kraken’ RBD induced binding broad sarbecoviruses, as well activity variant concern. nanocages nanomedicine approach potential confer heterotypic protection emergent zoonotic pathogens facilitate proactive pandemic protection.

Language: Английский

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An intranasal combination vaccine induces systemic and mucosal immunity against COVID-19 and influenza

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

Published: March 21, 2024

Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) influenza viruses continue to pose a global health burden. Thus, we developed chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 virus. When used as standalone intranasal immunization AdC68-HATRBD induced comprehensive potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, memory T cells, which protected mice from BA.5.2 pandemic H1N1 infections. heterologous booster, markedly improved protective response licensed or vaccine. Therefore, whether administered intranasally booster this vaccine is valuable strategy enhance overall efficacy by inducing robust systemic responses, thereby conferring lines immunological defenses for these two viruses.

Language: Английский

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A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 5, 2025

The Food and Drug Administration (FDA) has approved vaccines designed by GSK, Pfizer Moderna to protect high-risk populations against respiratory syncytial virus (RSV). These employ the pre-fusion F (pre-F) protein as immunogen. In this study, we explored an mRNA vaccine based on a modified pre-F called LC2DM-lipid nanoparticle (LC2DM-LNP). This features truncated version of that is anchored cell membrane. Our experiments in young old female mice revealed LC2DM-LNP elicited robust neutralizing antibody titers. Moreover, prompted Th1-skewed T-cell immune response rodent models. Female cotton rats immunized with demonstrated strong immunity RSV, without signs vaccine-enhanced disease (VERD), even cases breakthrough infection. Importantly, when administered pregnant rats, ensured transfer pre-F-specific antibodies offspring provided protection RSV increasing lung inflammation. findings suggest could serve alternative candidate for groups. Here authors design vaccine, expressing membrane-anchored stabilized protein, demonstrate humoral responses small animal models disease.

Language: Английский

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