The HLA-II immunopeptidome of SARS-CoV-2 DOI Creative Commons
Shira Weingarten-Gabbay, Da‐Yuan Chen, Siranush Sarkizova

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 43(1), P. 113596 - 113596

Published: Dec. 20, 2023

Targeted synthetic vaccines have the potential to transform our response viral outbreaks, yet design of these requires a comprehensive knowledge immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique from canonical proteins as well overlapping internal open reading frames. Most HLA-II colocalize with known CD4+ T cell epitopes disease 2019 patients, including reported immunodominant regions SARS-CoV-2 membrane protein. Overall, analyses show HLA-I pathways target distinct proteins, structural accounting for most peptidome nonstructural noncanonical majority peptidome. These findings highlight need vaccine incorporates multiple elements harboring CD8+ maximize effectiveness.

Language: Английский

An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission DOI Creative Commons
Julia M. Adler, Ricardo Martin Vidal, Christine Langner

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 2, 2024

Abstract The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways—the primary site infection and virus shedding. Here we compare efficacy a mucosal, replication-competent yet fully attenuated vaccine, sCPD9-ΔFCS, monovalent mRNA vaccine BNT162b2 preventing transmission variants B.1 Omicron BA.5 two scenarios. Firstly, assessed protective by exposing vaccinated male Syrian hamsters infected counterparts. Secondly, evaluated challenge from subsequently challenged naïve contacts. Our findings demonstrate that live-attenuated (LAV) sCPD9-ΔFCS significantly outperformed both results provide evidence for advantages locally administered LAVs over intramuscularly reducing transmission.

Language: Английский

Citations

17
A truncated pre-F protein mRNA vaccine elicits an enhanced immune response and protection against respiratory syncytial virus DOI Creative Commons
Min Lin, Yifan Yin, Xiaomeng Zhao

et al.

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

Citations

3
T cell immune memory after covid-19 and vaccination DOI Creative Commons
Lulu Wang, Alexander R. Nicols, Lance Turtle

et al.

BMJ Medicine, Journal Year: 2023, Volume and Issue: 2(1), P. e000468 - e000468

Published: Nov. 1, 2023

The T cell memory response is a crucial component of adaptive immunity responsible for limiting or preventing viral reinfection. after infection with the SARS-CoV-2 virus vaccination broad, and spans multiple proteins epitopes, about 20 in each individual. So far long lasting provides high level cross reactivity hence resistance to escape by variants virus, such as omicron variant. All current vaccine regimens tested produce robust responses, heterologous will probably enhance protective responses through increased breadth. could have major role protecting against severe covid-19 disease rapid clearance early presentation presence reactive cells might this protection. likely provide ongoing protection admission hospital death, development pan-coronovirus future proof new pandemic strains.

Language: Английский

Citations

34
Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history DOI Creative Commons
Hailey Hornsby, Alexander R. Nicols, Stéphanie Longet

et al.

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

Published: Aug. 21, 2023

Abstract Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections triple-vaccinated result poor induction omicron-specific prior infection is associated with dampening. Taking broad comprehensive approach, we characterize mucosal blood immunity to spike non-spike antigens following BA.1/BA.2 triple mRNA-vaccinated individuals, without We find most increase BA.1/BA.2/BA.5-specific neutralizing antibodies infection, but confirm magnitude post-omicron titres are higher infection-naive. In contrast, significant increases nasal responses, including activity against BA.5 spike, seen regardless history. Spike-specific T cells only infection-naive vaccinees; however, cell responses significantly previously-infected, who display maximally induced response highly cytotoxic CD8+ phenotype their 3 rd mRNA vaccine dose. Responses status. These findings suggest characterized enhancement can help protect future variants.

Language: Английский

Citations

31
T cell responses to SARS-CoV-2 infection and vaccination are elevated in B cell deficiency and reduce risk of severe COVID-19 DOI
Reza Zonozi, Lucy C. Walters, Aaron Shulkin

et al.

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(724)

Published: Nov. 29, 2023

Individuals with primary and pharmacologic B cell deficiencies have high rates of severe disease mortality from coronavirus 2019 (COVID-19), but the immune responses clinical outcomes after acute respiratory syndrome 2 (SARS-CoV-2) infection vaccination yet to be fully defined. Here, we evaluate cellular both SARS-CoV-2 in patients receiving anti-CD20 therapy rituximab (RTX) those low counts due common variable deficiency (CVID) disease. Assessment effector memory CD4 + CD8 T revealed elevated reactivity proliferative capacity cell–deficient individuals, particularly within compartment, comparison healthy controls. Evaluation demonstrates that RTX-treated individuals was associated about 4.8-fold reduced odds moderate or COVID-19 absence vaccine-induced antibodies. Analysis differentiation RTX administration increases relative frequency naïve cells, potentially by depletion CD20 dim which are primarily an terminal (TEMRA) phenotype. However, this also leads a reduction preexisting antiviral immunity. Collectively, these data indicate enhanced immunity accounts for hospitalization subsequent infection.

Language: Английский

Citations

29
Advanced technologies for the development of infectious disease vaccines DOI
Akash Gupta, Arnab Rudra,

Kaelan Reed

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(12), P. 914 - 938

Published: Oct. 21, 2024

Language: Английский

Citations

10
The Immunogenicity of Coxsackievirus A6 (D3a Sub‐Genotype) Virus‐Like Particle and mRNA Vaccines DOI Open Access
Huanhuan Lu, Jinbo Xiao, Jingdong Song

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

In recent years, coxsackievirus A6 (CVA6) has surpassed enterovirus A71 to become the main pathogen causing severe Hand, Foot, and Mouth disease (HFMD) in China with a substantial burden. However, there is currently no commercial CVA6 vaccine. The D3a genotype of predominant China. this study, virus-like particles (VLPs) mRNA vaccines based on sub-genotype were successfully developed. immunogenicity protective effects VLP combined Al(OH)3 CpG adjuvant indicated that VLP-induced neutralizing antibodies against three (D2, D3a, D3b) strains Institute Cancer Research (ICR) mice, combination two adjuvants enhanced cellular immunity. Passive immunization serum from mice immunized VLPs protected suckling lethal challenge both antiserum transfer maternal experiments. vaccine indicate it induces robust T-cell immunity was found cross-protect A10 infection mice. This first trial worldwide comparison CVA6. study provides theoretical basis for development enteroviruses formulation strategies.

Language: Английский

Citations

1
Vaccine process technology—A decade of progress DOI Creative Commons
Barry C. Buckland, Gautam Sanyal,

Todd Ranheim

et al.

Biotechnology and Bioengineering, Journal Year: 2024, Volume and Issue: 121(9), P. 2604 - 2635

Published: May 6, 2024

In the past decade, new approaches to discovery and development of vaccines have transformed field. Advances during COVID-19 pandemic allowed production billions vaccine doses per year using novel platforms such as messenger RNA viral vectors. Improvements in analytical toolbox, equipment, bioprocess technology made it possible achieve both unprecedented speed scale manufacturing. Macromolecular structure-function characterization technologies, combined with improved modeling data analysis, enable quantitative evaluation formulations at single-particle resolution guided design drug substances products. These advances play a major role precise assessment critical quality attributes delivered by newer platforms. Innovations label-free immunoassay technologies aid antigenic sites robust vitro potency assays. methods, along molecular techniques next-generation sequencing, will accelerate release all Process for real-time monitoring optimization process steps implementation quality-by-design principles faster next field continue advance, bringing together improve human health.

Language: Английский

Citations

7
T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases DOI Creative Commons

Xin Song,

Yongfeng Li,

Hongxia Wu

et al.

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

Citations

7
The Key to Increase Immunogenicity of Next-Generation COVID-19 Vaccines Lies in the Inclusion of the SARS-CoV-2 Nucleocapsid Protein DOI Creative Commons
Noe Juvenal Mendoza-Ramírez, Julio García‐Cordero, Gaurav Shrivastava

et al.

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

Citations

6