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1.
Emerg Microbes Infect ; 12(1): 2207670, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-20238651

ABSTRACT

SARS-CoV-2 Omicron subvariants have become the predominantly strain in most countries. However, the neutralizing activity of the human serum after Omicron-based vaccine booster against different SARS-CoV-2 variants is poorly understood. Here, we developed an update Omicron vaccine (SCoK-Omicron), based on the RBD-Fc fusion protein vaccine (SCoK) and RBD domain of Omicron BA.1. To assess cross-variant neutralizing activity in adults, 25 volunteers that have received three doses of SCoK and 25 volunteers with two doses of CoronaVac (inactive vaccine) were further boosted with a dose updated vaccine (SCoK-Omicron). The results of pseudovirus neutralization assays demonstrated that the booster potently induced the high-level of neutralizing antibody against SARS-CoV-2 Wild type, Delta and Omicron subvariants in adults. Further assays of single point mutations showed that K444T, L452R, N460K, or F486V was key mutations to cause immune evasion. Together, these data suggest that SCOK-Omicron can be used as a booster vaccine candidate in adults receiving subunit protein or inactivated vaccine in response to the epidemic of COVID-19 Omicron subvariants, and the mutation K444T, L452R, N460K, or F486V needs to be considered in future vaccine design.


Subject(s)
COVID-19 , Vaccines , Humans , Adult , SARS-CoV-2/genetics , COVID-19/prevention & control , Antibodies, Neutralizing , Antibodies, Viral
2.
Adv Sci (Weinh) ; : e2207474, 2023 May 10.
Article in English | MEDLINE | ID: covidwho-2316532

ABSTRACT

Vaccination is a cost-effective medical intervention. Inactivated whole virusor large protein fragments-based severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccines have high unnecessary antigenic load to induce allergenicity and/orreactogenicity, which can be avoided by peptide vaccines of short peptide fragments that may induce highly targeted immune response. However, epitope identification and peptide delivery remain the major obstacles in developing peptide vaccines. Here, a multi-source data integrated linear B-cell epitope screening strategy is presented and a linear B-cell epitope enriched hotspot region is identified in Spike protein, from which a monomeric peptide vaccine (Epitope25) is developed and applied to subcutaneously immunize wildtype BALB/c mice. Indirect ELISA assay reveals specific and dose-dependent binding between Epitope25 and serum IgG antibodies from immunized mice. The neutralizing activity of sera from vaccinated mice is validated by pseudo and live SARS-CoV-2 wild-type strain neutralization assays. Then a dissolvable microneedle array (DMNA) is developed to pain-freely deliver Epitope25. Compared with intramuscular injection, DMNA and subcutaneous injection elicit neutralizing activities against SARS-CoV-2 wild-type strain as demonstrated by live SARS-CoV-2 virus neutralization assay. No obvious damages are found in major organs of immunized mice. This study may lay the foundation for developing linear B-cell epitope-based vaccines against SARS-CoV-2.

3.
J Med Virol ; 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2232773

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel subset of coronavirus that causes coronavirus disease 2019 (COVID-19), but vaccine development is hampered by the high mutation of virus This article is protected by copyright. All rights reserved.

4.
Microchem J ; 186: 108329, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2165710

ABSTRACT

Platinum nanoparticles (PtNPs) have been attracted worldwide attention due to their versatile application potentials, especially in the catalyst and sensing fields. Herein, a facile synthetic method of triethanolamine (TEOA)-capped PtNPs (TEOA@PtNP) for electrochemiluminescent (ECL) and colorimetric immunoassay of SARS-CoV spike proteins (SARS-CoV S-protein, a target detection model) is developed. Monodisperse PtNPs with an average diameter of 2.2 nm are prepared by a one-step hydrothermal synthesis method using TEOA as a green reductant and stabilizer. TEOA@PtNPs can be used as a nanocarrier to combine with antigen by the high-affinity antibody, which leads to a remarkable inhibition of electron transfer efficiency and mass transfer processes. On the basis of its peroxidase-like activity and easy-biolabeling property, the TEOA@PtNP can be used to establish a colorimetric immunosensor of SARS-CoV S-protein thought catalyzing the reaction of H2O2 and 3,3',5,5'-tetramethylbenzidine (TMB). Especially, the Ru(bpy)3 2+ ECL reaction is well-achieved with the TEOA@PtNPs due to their great conductivity and loading abundant TEOA co-reactants, resulting in an enhancing ECL signal in immunoassay of SARS-CoV S-protein. As a consequence, two proposed methods could achieve sensitive detection of SARS-CoV S-protein in wide ranges, the colorimetric and ECL detection limits were as low as 8.9 fg /mL and 4.2 fg /mL (S/N = 3), respectively. We believe that the proposed colorimetric and ECL immunosesors with high sensitivity, good reproducibility, and good stability will be a promising candidate for a broad spectrum of applications.

6.
Clin Transl Med ; 12(9): e1016, 2022 09.
Article in English | MEDLINE | ID: covidwho-2027332

ABSTRACT

BACKGROUND: To determine an appropriate dose of, and immunization schedule for, a vaccine SCoK against COVID-19 for an efficacy study; herein, we conducted randomized controlled trials to assess the immunogenicity and safety of this vaccine in adults. METHODS: These randomized, double-blind, placebo-controlled phase 1 and 2 trials of vaccine SCoK were conducted in Binhai District, Yan City, Jiangsu Province, China. Younger and older adult participants in phase 1 and 2 trials were sequentially recruited into different groups to be intramuscularly administered 20 or 40 µg vaccine SCoK or placebo. Participants were enrolled into our phase 1 and 2 studies to receive vaccine or placebo. RESULTS: No serious vaccine-related adverse events were observed in either trial. In both trials, local and systemic adverse reactions were absent or mild in most participants. In our phase 1 and 2 studies, the vaccine induced significantly increased neutralizing antibody responses to pseudovirus and live SARS-CoV-2. The vaccine induced significant neutralizing antibody responses to live SARS-CoV-2 on day 14 after the last immunization, with NT50s of 80.45 and 92.46 in participants receiving 20 and 40 µg doses, respectively; the seroconversion rates were 95.83% and 100%. The vaccine SCoK showed a similar safety and immunogenicity profiles in both younger participants and older participants. The vaccine showed better immunogenicity in phase 2 than in phase 1 clinical trial. Additionally, the incidence of adverse reactions decreased significantly in phase 2 clinical trial. The vaccine SCoK was well tolerated and immunogenic.


Subject(s)
COVID-19 Vaccines , COVID-19 , Aged , Antibodies, Neutralizing , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Randomized Controlled Trials as Topic , SARS-CoV-2
7.
Front Neurosci ; 15: 704537, 2021.
Article in English | MEDLINE | ID: covidwho-1365551

ABSTRACT

Socially responsible investment (SRI) is an emerging philosophy that integrates social and environmental impacts into investment considerations, and it has gradually developed into an important form of investment. Previous studies have shown that both financial and non-financial motivations account for SRI behaviors, but it is unclear whether the non-financial motive to adopt SRI derives from investors' altruism. This study uses neuroscientific techniques to explore the role of altruism in SRI decision-making. Given that existing evidence has supported the involvement of the right temporoparietal junction (rTPJ) in altruism and altruistic behaviors, we used transcranial direct current stimulation (tDCS) to temporarily modulate activity in the rTPJ and tested its effect on charitable donations and SRI behaviors. We found that anodal stimulation increased the subjects' donations, while cathodal stimulation decreased them, suggesting that tDCS changed the subjects' levels of altruism. More importantly, anodal stimulation enhanced the subjects' willingness to make SRIs, while cathodal stimulation did not have a significant impact. These findings indicate that altruism plays an important role in SRI decision-making. Furthermore, cathodal stimulation changed the subjects' perceived effectiveness of charitable donation but not that of socially responsible fund. This result may help explain the inconsistent effects of cathodal stimulation on charitable donations and SRI behaviors. The main contribution of our study lies in its pioneering application of tDCS to conduct research on SRI behaviors and provision of neuroscientific evidence regarding the role of altruism in SRI decision-making.

8.
J Adv Res ; 37: 209-219, 2022 03.
Article in English | MEDLINE | ID: covidwho-1330938

ABSTRACT

Introduction: The SARS-CoV-2 pandemic has endangered global health, the world economy, and societal values. Despite intensive measures taken around the world, morbidity and mortality remain high as many countries face new waves of infection and the spread of new variants. Worryingly, more and more variants are now being identified, such as 501Y.V1 (B.1.1.7) in the UK, 501Y.V2 (B.1.351) in South Africa, 501Y.V3 in Manaus, Brazil, and B.1.617/B.1.618 in India, which could lead to a severe epidemic rebound. Moreover, some variants have a stronger immune escape ability. To control the new SARS-CoV-2 variant, we may need to develop and redesign new vaccines repeatedly. So it is important to investigate how our immune system combats and responds to SARS-CoV-2 infection to develop safe and effective medical interventions. Objectives: In this study, we performed a longitudinal and proteome-wide analysis of antibodies in the COVID-19 patients to revealed some immune processes of COVID-19 patients against SARS-CoV-2 and found some dominant epitopes of a potential vaccine. Methods: Microarray assay, Antibody depletion assays, Neutralization assay. Results: We profiled a B-cell linear epitope landscape of SARS-CoV-2 and identified the epitopes specifically recognized by either IgM, IgG, or IgA. We found that epitopes more frequently recognized by IgM are enriched in non-structural proteins. We further identified epitopes with different immune responses in severe and mild patients. Moreover, we identified 12 dominant epitopes eliciting antibodies in most COVID-19 patients and identified five key amino acids of epitopes. Furthermore, we found epitope S-82 and S-15 are perfect immunogenic peptides and should be considered in vaccine design. Conclusion: This data provide useful information and rich resources for improving our understanding of viral infection and developing a novel vaccine/neutralizing antibodies for the treatment of SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Epitopes , Humans , Immunity, Humoral , Immunoglobulin M , Proteome
10.
Science ; 369(6511): 1603-1607, 2020 09 25.
Article in English | MEDLINE | ID: covidwho-690532

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Disease Models, Animal , Mice , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Administration, Intranasal , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Female , High-Throughput Nucleotide Sequencing , Humans , Immunogenicity, Vaccine , Lung/virology , Lung Diseases, Interstitial/virology , Mice, Inbred BALB C , Mice, Transgenic , Mutation , Peptidyl-Dipeptidase A/genetics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , Viral Vaccines/administration & dosage , Virulence/genetics
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