Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice

iScience, Год журнала: 2022, Номер 25(12), С. 105479 - 105479

Опубликована: Ноя. 2, 2022

Язык: Английский

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Plant-Derived Extracellular Vesicles as a Delivery Platform for RNA-Based Vaccine: Feasibility Study of an Oral and Intranasal SARS-CoV-2 Vaccine

Pharmaceutics, Год журнала: 2023, Номер 15(3), С. 974 - 974

Опубликована: Март 17, 2023

Plant-derived extracellular vesicles (EVs) may represent a platform for the delivery of RNA-based vaccines, exploiting their natural membrane envelope to protect and deliver nucleic acids. Here, EVs extracted from orange (Citrus sinensis) juice (oEVs) were investigated as carriers oral intranasal SARS-CoV-2 mRNA vaccine. oEVs efficiently loaded with different molecules (coding N, subunit 1 full S proteins) was protected degrading stress (including RNase simulated gastric fluid), delivered target cells translated into protein. APC stimulated mRNAs induced T lymphocyte activation in vitro. The immunization mice S1 via routes administration including intramuscular, humoral immune response production specific IgM IgG blocking antibodies cell response, suggested by IFN-γ spleen lymphocytes peptide. Oral also triggered IgA, mucosal barrier adaptive response. In conclusion, plant-derived useful mRNA-based vaccines administered not only parentally but orally intranasally.

Язык: Английский

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Pan‐Variant SARS‐CoV‐2 Vaccines Induce Protective Immunity by Targeting Conserved Epitopes

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Abstract The development of a globally effective COVID‐19 vaccine faces significant challenges, particularly in redirecting the B‐cell response from immunodominant yet variable regions viral proteins toward their conserved domains. To address this, an integrated strategy is implemented that combines classical epitope prediction with protein‐antibody cluster docking and antibody titer analysis 30 vaccinated convalescent individuals. This approach yields stable immunoprevalent epitopes capable eliciting robust responses BALB/c mice effectively neutralizing pseudoviruses expressing Spike protein SARS‐CoV‐2 variants concern, including Alpha, Beta, Gamma, Delta, Omicron. achieve broader T‐cell‐based immune response, promiscuous T‐cell are identified by integrating predictions, differential scanning fluorimetry, peptide‐MHC structural analysis. Unique peptides MHC‐anchoring residues identified, enabling binding to spectrum MHC‐I MHC‐II haplotypes. These elicit strong interferon gamma human peripheral blood mononuclear cells demonstrate cross‐species efficacy activating both CD4+ CD8+ T‐cells mice. Collectively, these findings highlight significance innovative strategies targeting immunodominant/immunoprevalent drive broad humoral cellular against wide range variants.

Язык: Английский

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Rerouting therapeutic peptides and unlocking their potential against SARS-CoV2

3 Biotech, Год журнала: 2025, Номер 15(5)

Опубликована: Апрель 4, 2025

Язык: Английский

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Prophylactic efficacy of an intranasal spray with 2 synergetic antibodies neutralizing Omicron

JCI Insight, Год журнала: 2024, Номер 9(7)

Опубликована: Апрель 7, 2024

BACKGROUNDAs Omicron is prompted to replicate in the upper airway, neutralizing antibodies (NAbs) delivered through inhalation might inhibit early-stage infection respiratory tract. Thus, elucidating prophylactic efficacy of NAbs via nasal spray addresses an important clinical need.METHODSThe applicable potential a cocktail containing 2 was characterized by testing its potency, synergetic mechanism, emergency protective and therapeutic hamster model, pharmacokinetics/pharmacodynamic (PK/PD) human cavity.RESULTSThe displayed broad against Omicron, they could structurally compensate each other blocking Spike-ACE2 interaction. When administrated intranasal mucosal route, this demonstrated profound prevention hamsters challenged with authentic BA.1. The investigator-initiated trial healthy volunteers confirmed safety PK/PD NAb spray. Nasal samples from participants receiving 4 administrations over course 16 hours potent neutralization BA.5 ex vivo pseudovirus assay.CONCLUSIONThese results demonstrate that provides good basis for infections.TRIAL REGISTRATIONwww.chictr.org.cn, ChiCTR2200066525.FUNDINGThe National Science Technology Major Project (2017ZX10202203), Key Research Development Program China (2018YFA0507100), Guangzhou Laboratory (SRPG22-015), Lingang (LG202101-01-07), Commission Shanghai Municipality (YDZX20213100001556), Emergency & Chongqing (cstc2021jscx-fyzxX0001).

Язык: Английский

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Design of the conserved epitope peptide of SARS-CoV-2 spike protein as the broad-spectrum COVID-19 vaccine

Applied Microbiology and Biotechnology, Год журнала: 2024, Номер 108(1)

Опубликована: Окт. 16, 2024

Our previous study has found that monoclonal antibodies targeting a conserved epitope peptide spanning from residues 1144 to 1156 of SARS-CoV-2 spike (S) protein, namely S(1144-1156), can broadly neutralize all the prevalent strains, including wild type, Alpha, Epsilon, Delta, and Gamma variants. In study, S(1144-1156) was conjugated with bovine serum albumin (BSA) formulated Montanide ISA 51 adjuvant for inoculation in BALB/c mice its potential as vaccine candidate. Results showed titers S protein-specific IgGs neutralizing mouse sera against various variants, Omicron sublineages, were largely induced along three doses immunization. The significant release IFN-γ IL-2 also observed by ELISpot assays through stimulating vaccinated splenocytes peptide. Furthermore, vaccination S(1143-1157)- S(1142-1158)-EGFP fusion proteins elicit more than S(1144-1156)-EGFP protein. Interestingly, antisera collected inoculated exhibited better efficacy BA.2.86 JN.1 subvariants BA.1, BA.2, XBB subvariants. Since amino acid sequences are highly among immunogen containing core be designed effective COVID-19 vaccine. KEY POINTS: • Inoculation induce bnAbs stimulated splenocytes. S(1143-1157) S(1142-1158) vaccines nAbs mice.

Язык: Английский

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Features of Highly Homologous T-Cell Receptor Repertoire in the Immune Response to Mutations in Immunogenic Epitopes

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12591 - 12591

Опубликована: Ноя. 23, 2024

CD8+ T-cell immunity, mediated through interactions between human leukocyte antigen (HLA) and the receptor (TCR), plays a pivotal role in conferring immune memory protection against viral infections. The emergence of SARS-CoV-2 variants presents significant challenge to existing population immunity. While numerous mutations have been associated with evasion from T cells, molecular effects most on epitope-specific TCR recognition remain largely unexplored, particularly for repertoires characterized by common TCRs. In this study, we investigated an HLA-A*24-restricted NYN epitope (Spike448-456) that elicits broad highly homologous cell responses COVID-19 patients. Eleven naturally occurring epitope, all which retained surface presentation HLA, were tested four transgenic Jurkat reporter lines. Our findings demonstrate that, exception L452R combined mutation L452Q + Y453F, these minimal impact avidity peptide-specific Additionally, observed similar responded differently mutant epitopes demonstrated cross-reactivity unrelated VYF (ORF3a112-120). results contradict idea limited diversity are insufficient provide emerging variants.

Язык: Английский

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Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination

Cell Reports, Год журнала: 2023, Номер 42(5), С. 112470 - 112470

Опубликована: Апрель 21, 2023

Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression SARS-CoV-2 spike protein infection angiotensin-converting enzyme (ACE)-2-transduced B lines to evaluate overall in a small cohort recovered COVID-19 patients uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV antigen can be used as an alternative naturally antigens. addition, the system cross-reactivity memory cells variants concern (VOCs) identify epitope escape mutants. Finally, our data both natural vaccination could induce multi-functional remaining despite identification mutations.

Язык: Английский

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Identification of Closed Linear Epitopes in S1-RBD and S2-HR1/2 of SARS-CoV-2 Spike Protein Able to Induce Neutralizing Abs

Vaccines, Год журнала: 2023, Номер 11(2), С. 287 - 287

Опубликована: Янв. 28, 2023

SARS-CoV-2 has evolved as several variants. Immunization to boost the Ab response Spike antigens is effective, but similar vaccines could not enhance efficacy enough. Effective responses against human ACE2 (hACE2)-mediated infection of emerging variants are needed. We identified closed linear epitopes molecule that induced neutralizing Abs (nAbs) both S1-RBD, responsible for attachment hACE2, and S2-HR1/2, in convalescents vaccine recipients. They inhibited a pseudo-virus mediated by hACE2 pathway. The epitope sequences included #7 (aa411-432), #11 (aa459-480) #111 (aa1144-1161), S1-RBD S2-HR2. Epitope was conserved Wuhan variant strains, whereas were carried mutations K417N S477N/T478K Omicron BA.4/5. These recognized original epitope-specific Abs. RBD HR2 neither contained, nor overlapped with, those antibody-dependent enhancement infection. sublingual administration multiple epitope-conjugated increased IgG IgA specific mice pre-immunized subcutaneously. findings indicated S2-HR2 infections boosts with protection nAbs wide range

Язык: Английский

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Study on immunogenicity of Lrp subunit vaccine against Vibrio alginolyticus in pearl gentian grouper(♀Epinephelus fuscoguttatus ×♂Epinephelus lanceolatus)

Frontiers in Marine Science, Год журнала: 2023, Номер 10

Опубликована: Фев. 22, 2023

Vibrio alginolyticus is the main pathogen causing vibriosis in pearl gentian grouper, which has caused significant financial losses to farmers. To develop a sustainable and effective subunit vaccine for prevention control of vibriosis, Lrp recombinant protein from V. was expressed purified this study. Western Blotting ELISA demonstrated that with relatively higher antigenicity can be used as an antigen vaccine. Chitosan oligosaccharide (COS) very potential aquatic adjuvant boost immunological protection Therefore, evaluate immune response against we designed group Lrp+COS experimental groups PBS group. Immunological testing revealed grouper serum had significantly levels particular antibody IgM, lysozyme (LZM), catalase (CAT), superoxide dismutase (SOD) than Additionally, groupers showed gene expression levels, namely IgM , CD8α MHC-Iα IL-1β IL-16 TNF-α . After challenge experiment, rates were respectively enhanced 60% 72%. The aforementioned findings group’s impact superior promising candidate management vibrio infection grouper.

Язык: Английский

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