Safety, immunogenicity, and protective effective of inhaled COVID‐19 vaccines: A systematic review and meta‐analysis

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(4)

Published: April 1, 2024

This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID-19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, Web Science up 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed compared using random effects common model. Of 15 studies, 11 analyzed 13 immunogenicity, 3 effective. The results showed a favorable safety profile ICVs for primary vaccination series, however it does not always seem produce expected immune response Meta-analysis booster vaccinations (BVs) that levels neutralizing antibody Geometric mean titer (nAb-GMT) aerosolised Ad5-nCoV (AAd5-nCoV) all higher than those inactivated vaccine (INA-nCoV) (standard difference (SMD) = 2.32; CI: 1.96-2.69) intramuscular (IMAd5-nCoV) (SMD 0.31; 0.14-0.48) against original strain SARS-CoV-2. Importantly, we also observed similar in omicron variant. In addition, ICV BVs has high mucosal immunity IgA antibodies. risk adverse events comparable or lower AAd5-nCoV INA-nCoV IMAd5-nCoV. Current evidence shows well. dose had (including immunity) provided protection caused by SARS-CoV-2 Further studies are needed investigate long-term intranasal various types ICVs.

Language: Английский

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Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by lactoferricin

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 23, 2022

In addition to vaccines, there is an urgent need for supplemental antiviral therapeutics dampen the persistent COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The transmembrane protease serine 2 (TMPRSS2), that responsible proteolytic priming of SARS-CoV-2 spike protein, appears as a rational therapeutic target. Accordingly, selective inhibitors TMPRSS2 represent potential tools prevention and treatment COVID-19. Previously, we identified human milk glycoprotein lactoferrin natural inhibitor plasminogen conversion plasmin, homologous TMPRSS2. Here, tested whether lactoferricin, biologically active peptide produced pepsin-mediated digestion lactoferrin, together with synthetic peptides derived from were able block infection. Particularly, revealed both lactoferricin N-terminal pLF1 significantly inhibited: i) activity ii) processing iii) infection SARS-CoV-2-permissive cells. Thus, feasible candidates supporting

Language: Английский

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New insights into human immune memory from SARS‐CoV‐2 infection and vaccination

Allergy, Journal Year: 2022, Volume and Issue: 77(12), P. 3553 - 3566

Published: Sept. 1, 2022

Abstract Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting mass morbidity estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique innovative means to identify infected individuals, technologies evaluate immune responses infection vaccination, new therapeutic strategies treat individuals. Never before immunology so critically at forefront of combatting a global pandemic. It now become evident that not just antibody responses, but formation durability memory cells following vaccination are associated protection against severe disease from infection. Furthermore, emergence concern (VoC) highlight need for immunological markers quantify protective capacity Wuhan‐based vaccines. Thus, harnessing modulating response is key successful treatment disease. We here review latest knowledge about generation natural provide insights into attributes may protect variants.

Language: Английский

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Safety and Immunogenicity of the Convacell® Recombinant N Protein COVID-19 Vaccine

Vaccines, Journal Year: 2024, Volume and Issue: 12(1), P. 100 - 100

Published: Jan. 19, 2024

We have developed Convacell®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell’s® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were frequency adverse effects (AEs) titers specific anti-N IgGs induced by vaccination; secondary included nature immune response. Convacell® demonstrated high safety in I with no severe AEs detected, 100% seroconversion day 42 sustained for 350 days IgG levels II. also a fused cellular humoral Phase results showed significant post-vaccination increases circulating N protein-specific IFNγ+-producing PBMC quantities among 438 volunteers. same level immunological efficacy single double dose vaccination regimens, including elderly patients. studies indicate that is safe highly immunogenic.

Language: Английский

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Vaccine Based on Recombinant Fusion Protein Combining Hepatitis B Virus PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived Receptor Binding Domain Strongly Induces Omicron-Neutralizing Antibodies in a Murine Model

Vaccines, Journal Year: 2024, Volume and Issue: 12(3), P. 229 - 229

Published: Feb. 23, 2024

Background: COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a recurrent endemic disease affecting whole world. Since November 2021, Omicron and its subvariants have dominated in spread of disease. In order to prevent courses disease, vaccines are needed boost maintain antibody levels capable neutralizing Omicron. Recently, we produced characterized SARS-CoV-2 vaccine based on recombinant fusion protein consisting hepatitis B virus (HBV)-derived PreS two wild-type RBDs. Objectives: To develop PreS-RBD which induces high Omicron-specific antibodies. Methods: We designed, produced, compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix W-PreS-W O-PreS-O) chimeric (i.e., W-PreS-O) subunit vaccines. Immunogens were vitro using chemical methods, mass spectrometry, circular dichroism combination with thermal denaturation immunological methods. addition, BALB/c mice immunized aluminum–hydroxide-adsorbed proteins aluminum hydroxide alone placebo) study specific cytokine responses, safety neutralization. Results: Defined pure immunogens could be significant quantities as secreted folded mammalian cells. The antibodies induced after vaccination different doses strain-specific, reacted RBD dose-dependent manner resulted mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG comparable, but W-PreS-O-induced neutralization titers against (median VNT50: 5000) seven- twofold higher than W-PreS-W- O-PreS-O-specific ones, respectively, they six-fold those vaccine. Conclusion: Among tested immunogens, vaccine, W-PreS-O, highest Thus, W-PreS-O seems highly promising COVID-19 candidate for further preclinical clinical evaluation.

Language: Английский

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Combined assessment of S‐ and N‐specific IL‐2 and IL‐13 secretion and CD69 neo‐expression for discrimination of post–infection and post‐vaccination cellular SARS‐CoV‐2‐specific immune response

Allergy, Journal Year: 2022, Volume and Issue: 77(11), P. 3408 - 3425

Published: June 12, 2022

Abstract Background Antibody‐based tests are available for measuring SARS‐CoV‐2‐specific immune responses but fast T‐cell assays remain scarce. Robust T cell‐based needed to differentiate specific cellular after infection from those vaccination. Methods One hundred seventeen individuals (COVID‐19 convalescent patients: n = 40; SARS‐CoV‐2 vaccinees: 41; healthy controls: 36) were evaluated (proliferation, Th1, Th2, Th17, and inflammatory cytokines, activation‐induced marker [AIM] expression) by incubating purified peripheral blood mononuclear cells (PBMC) or whole (WB) with peptides (S, N, M), vaccine antigens (tetanus toxoid, tick borne encephalitis virus) polyclonal stimuli ( Staphylococcal enterotoxin, phytohemagglutinin). Results N‐peptide mix stimulation of WB identified the combination IL‐2 IL‐13 secretion as superior IFN‐γ discriminate between COVID‐19‐convalescent patients controls p < .0001). Comparable results obtained M‐ S‐peptides, latter almost comparably recalled IL‐2, IFN‐γ, in vaccinees. Analysis 10 months opposed weeks COVID‐19, not allergic disease status, positively correlated recall responses. cytokine proliferation PBMC. Antigen‐induced neo‐expression C‐type lectin CD69 on CD4 + .0001) CD8 .0002) informed best about exposure status additional benefit coming CD25 upregulation. Conclusion Along N‐ S‐peptide‐induced neo‐expression, we suggest include type 2 T‐cellular

Language: Английский

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The preS-Based Recombinant Vaccine VVX001 Induces Hepatitis B Virus Neutralizing Antibodies in a Low-Responder to HBsAg-Based HBV Vaccines

Published: July 26, 2024

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes binding site HBV to its receptor on hepatocytes. We investigated if non-responsiveness after repeated vaccinations can be overcome by immunization VVX001 (i.e., Alum-adsorbed BM325, component BM32). Methods: A subject failing develop protective HBV-specific immunity vaccination received five monthly injections 20 µg VVX001. PreS-specific antibody responses were measured ELISA and micro-array technology. Serum reactivity subviral particles different genotypes was determined sandwich ELISA. T cell monitored CFSE staining subsequent FACS analysis. neutralization assessed using cultured HBV-infected HepG2 cells. Results: Vaccination induced strong sustained preS-specific response composed mainly IgG1 subclass. IgG antibodies primarily directed N-terminal part NTCP attachment site. sub-viral well preS-derived peptides comparable for A-H. pronounced CD3+CD4+ lymphocytes specific complete injection course remaining up one year last found. Maximal (98.4%) in vitro achieved 1 month which correlated maximal preS. Conclusion: Our data suggest that may used preventive against even non-responders vaccines.

Language: Английский

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Vaccine Based on Recombinant Fusion Protein Combining HBV PreS with SARS-CoV-2 Wild-Type- and Omicron-Derived RBD Strongly Induces Omicron-Neutralizing Antibodies

Published: Jan. 16, 2024

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent courses of disease, vaccines needed boost maintain antibody levels capable neutralizing Omicron. Recently we produced characterized SARS-CoV-2 vaccine based on recombinant fusion protein consisting hepatitis B virus (HBV)-derived PreS two wild-type RBDs. Objectives: To develop PreS-RBD which induces high Omicron-specific antibodies. Methods: We designed, produced, compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix W-PreS-W O-PreS-O) chimeric (i.e., W-PreS-O) subunit vaccines. Immunogens were in vitro chemical methods, mass-spectrometry, circular dichroism combination with thermal denaturation immunological methods. addition, BALB/c mice immunized aluminum hydroxide-adsorbed proteins hydroxide alone placebo) study specific cytokine responses, safety neutralization. Results: Defined pure immunogens could be large amounts as secreted folded mammalian cells. Antibodies induced after vaccination different doses strain-specific, reacted RBD dose-dependent manner resulted mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG comparable but W-PreS-O-induced neutralization titers against (median VNT50: 5000) 7- 2-fold higher than W-PreS-W- O-PreS-O-specific ones, respectively 6-fold those vaccine. Conclusion: Among tested immunogens, vaccine, W-PreS-O, highest Thus, W-PreS-O seems highly promising candidate for further preclinical clinical evaluation.

Language: Английский

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Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5104 - 5104

Published: March 7, 2023

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities induced antibodies not fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before after two immunizations Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) studied on a panel micro-arrayed recombinant folded unfolded severe acute respiratory syndrome 2 (SARS-CoV-2) proteins 46 peptides spanning spike protein (S) by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability Gam-COVID-Vac-induced to inhibit binding receptor-binding domain (RBD) its receptor angiotensin converting enzyme (ACE2) investigated molecular interaction (MIA). virus-neutralizing capacity pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 Omicron. We found that vaccination significant increases IgG1 other IgG subclasses against S, subunit 1 (S1), (S2), RBD comparable manner subjects. Virus highly correlated vaccination-induced specific novel peptide (i.e., 12). Peptide located close N-terminal part S1 may potentially be involved transition pre- post-fusion conformation protein. In summary, S-specific naive manner. Besides RBD, N-terminus were also associated virus-neutralization.

Language: Английский

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Impfstoffkonzepte: Tot oder lebendig

Nachrichten aus der Chemie, Journal Year: 2024, Volume and Issue: 72(2), P. 28 - 30

Published: Jan. 31, 2024

Abstract Neue Ansätze gegen Sars‐CoV‐2 berücksichtigen künftige Virusvarianten und besondere Patientengruppen, etwa Immunsupprimierte. Zu Entwicklungsstrategien gehören Computersimulationen sowie die Beobachtung realer Viren ihrer Evolution im Hochsicherheitslabor.

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