STING agonist-based ER-targeting molecules boost antigen cross-presentation

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: March 26, 2025

CD8+ T cell immune responses are critical for combating infectious diseases and tumours1–3. Antigen cross-presentation, primarily occurring at the endoplasmic reticulum (ER) of dendritic cells, is essential protein-based vaccines to induce responses4. Current efforts have focused on antigen delivery tissue cellular levels, whereas subcellular has been limited facilitating escape from lysosomes into cytosol. In absence a small-sized high-affinity ER-targeting molecule, importance 'last mile' cytosol ER remains elusive. Here we developed stimulator interferon genes (STING) agonist-based molecules (SABER), which effectively deliver antigens cluster key machinery in cross-presentation form microreactors by folding membrane. Conjugation SABER various substantially enhances induction tumour neoantigens conserved viral epitopes, far exceeding that achieved mixtures with STING agonists or conventional adjuvants. also retains potent adjuvant effect, enhancing ability SARS-CoV-2 subunit vaccine broadly neutralizing antibodies. This study provides system adjuvant, demonstrating precise targeting last mile can lead qualitative leap. reticulum-targeting be conjugated directly onto them pathway, improving against tumours viruses.

Language: Английский

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T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases

Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1181 - 1181

Published: Oct. 17, 2024

With the development of novel vaccine strategies, T-cell epitope-based vaccines have become promising prophylactic and therapeutic tools against infectious diseases that cannot be controlled via traditional vaccines. leverage specific immunogenic peptides to elicit protective responses pathogens. Compared vaccines, they provide superior efficacy safety, minimizing risk adverse side effects. In this review, we summarized compared prediction identification methods epitopes. By integrating bioinformatic experimental validation, efficient precise screening epitopes can achieved. Importantly, delved into approaches diverse comparing their merits demerits, as well discussing prevalent challenges perspectives in applications. This review offers fresh for formulation safe efficacious devastating which no are currently available.

Language: Английский

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The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein

Journal of Immunology Research, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 18

Published: May 29, 2024

Vaccination is one of the most effective prophylactic public health interventions for prevention infectious diseases such as coronavirus disease (COVID-19). Considering ongoing need new COVID-19 vaccines, it crucial to modify our approach and incorporate more conserved regions severe acute respiratory syndrome 2 (SARS-CoV-2) effectively address emerging viral variants. The nucleocapsid protein a structural SARS-CoV-2 that involved in replication immune responses. Furthermore, this offers significant advantages owing minimal accumulation mutations over time inclusion key T-cell epitopes critical immunity. A novel strategy may be suitable generation vaccines against use combination antigens, including spike proteins, elicit robust humoral potent cellular responses, along with long-lasting strategic multiple antigens aims enhance vaccine efficacy broaden protection viruses, their response from other long-lasting, can persist up 11 years post-infection. Thus, incorporation nucleocapsids (N) into design adds an important dimension vaccination efforts holds promise bolstering ability combat effectively. In review, we summarize preclinical studies evaluated antigen. This study discusses alone its or proteins SARS-CoV-2.

Language: Английский

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mRNA-LNP vaccine-induced CD8+ T cells protect mice from lethal SARS-CoV-2 infection in the absence of specific antibodies

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(6), P. 1790 - 1804

Published: April 11, 2024

The role of CD8

Language: Английский

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Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

动物学研究, Journal Year: 2024, Volume and Issue: 45(4), P. 747 - 766

Published: Jan. 1, 2024

The distribution of the immune system throughout body complicates

Language: Английский

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Effector CD8 T cell differentiation in primary and breakthrough SARS-CoV-2 infection in mice

Communications Biology, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 8, 2025

The nature of the effector and memory T cell response in lungs following acute SARS-CoV-2 infections remains largely unknown. To define pulmonary T-cell to COVID-19, we compared responses influenza A virus (IAV) mice. Both viruses elicited potent lungs, but cells showed exaggerated contraction SARS-CoV-2-infected Specifically, unlike T-bet/EOMES-driven transcription program IAV SARS-CoV-2-specific CD8 embarked on a STAT-3-centric transcriptional program, defining characteristic pro-fibro-inflammatory program: limited cytotoxicity, diminished expression tissue-protective inhibitory receptors (PD-1, LAG-3, TIGIT), augmented mucosal imprinting (CD103). Circulating CD45RO+HLA-DR+ hospitalized COVID-19 patients expressed elevated levels STAT-3 low TIGIT. IL-6 blockade experiments implicated induction downregulation PD-1 primary cells. Memory specific single epitope, induced by vaccination, differentiated into cytotoxic effectors high CD103, effectively reducing viral burden breakthrough infection. Our findings have implications for developing targeted immunotherapies mitigate immunopathology promote protective immunity SARS-CoV-2. infection triggers atypical lungs; recall + epitope (SIINFEKL) vaccination can reduce loads

Language: Английский

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Characterizing HLA-A2-restricted CD8+ T-cell epitopes and immune responses to Omicron variants in SARS-CoV-2-inactivated vaccine recipients

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 18, 2025

Recent surveillance has identified the emergence of SARS-CoV-2 Omicron ariant, which exhibits ability to evade multiple neutralizing antibodies generated by prior infection or vaccination. However, significant knowledge gaps remain regarding CD8 T-cell immune reactivity variant. This study aims evaluate characteristics HLA-A2-restricted epitopes from variant and analyze epitope-specific responses inactivated vaccines. We conducted a comprehensive analysis vaccines, focusing on derived Mutant were evaluated for their impact antigen presentation reactivity. Additionally, we screened that exhibited reduced following Our findings revealed mutant in led escape diminished responses. two associated with decreased post-Omicron emergence. Notably, discovered an S protein epitope, 67A>V, demonstrated similar proportions specificity between ancestral strains, suggesting its conservation potential immunogenicity vaccine development. Furthermore, third dose significantly increased number T cells, underscoring importance booster doses enhancing cellular against highlights through epitope mutations, while also identifying conserved utility design. The observed increase cells emphasizes critical role additional vaccinations strengthening immunity emerging variants. These provide valuable insights development next-generation vaccines targeting optimizing strategies.

Language: Английский

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Intranasal administration of unadjuvanted SARS‐CoV‐2 spike antigen boosts antigen‐specific immune responses induced by parenteral protein subunit vaccine prime in mice and hamsters

European Journal of Immunology, Journal Year: 2024, Volume and Issue: 54(6)

Published: April 1, 2024

Abstract With the continued transmission of SARS‐CoV‐2 across widely vaccinated populations, it remains important to develop new vaccines and vaccination strategies capable providing protective immunity limiting spread disease. Heterologous prime‐boost based on selection different vaccine formulations administration routes for priming booster doses presents a promising strategy inducing broader immune responses in key systemic respiratory mucosal compartments. Intranasal can induce at site infection; however, lack clinically approved adjuvants makes difficult robust with protein subunit vaccines. Herein, we evaluated immunogenicity heterologous regimens mice hamsters parenteral antigen combination sulfated lactosylarchaeol (SLA) archaeosomes, liposome adjuvant comprised single semisynthetic archaeal lipid, followed by an intranasally administered unadjuvanted spike antigen. increased serum spike‐specific IgG titers spike‐neutralizing activity compared nonboosted animals. Spike‐specific IgA were also detected bronchoalveolar lavage fluid lungs that received intranasal boost. In hamsters, boost showed high efficacy against infection protecting from body weight loss reducing viral nasal turbinate. Overall, our intramuscular prime‐intranasal SLA‐adjuvanted spike, respectively, demonstrated potential promote antigen‐specific responses.

Language: Английский

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Lessons from COVID‐19: Aspects of prevention, therapeutics, and diagnostics against SARS‐CoV‐2 with special focus on JN.1 and XBB sublineages

MedComm – Future Medicine, Journal Year: 2024, Volume and Issue: 3(2)

Published: June 1, 2024

Abstract The end of second decade in the 21st century witnessed a prominent disease outbreak caused by novel coronavirus SARS‐CoV‐2 (including most diverse omicron subvariants), where death toll crossed boundary 6.9 million across globe December 19, 2023. All spheres central dogma molecular biology and host‒pathogen interaction was explored to find ways diagnostics, isolation, curtailment, therapy. Above all, diagnostics therapeutics against COVID‐19 took an enormous jump, which needs be evaluated for accuracy feasibility requires serious compilation current future generations. With same objective, this review encompasses including prevention practiced proposed during handling pandemic globe. It involves role mutations viruses subsequent epitope mapping with potential immune escape mechanisms variants conservancy T‐cell epitopes has also been highlighted. efficacy antigen/antibody‐based RT‒PCR‐ NGS‐based confirmation pathogen presence, imaging (X‐ray/CT‐scan) symptoms damage assessment thoroughly filtered. possibility errors their cause consequences have presented ease readers further improvisers.

Language: Английский

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A multifaceted approach for identification, validation, and immunogenicity of naturally processed and in silico-predicted highly conserved SARS-CoV-2 peptides

Vaccine, Journal Year: 2023, Volume and Issue: 42(2), P. 162 - 174

Published: Dec. 16, 2023

Language: Английский

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