T-cell immunity to SARS-CoV-2: what if the known best is not the optimal course for the long run? Adapting to evolving targets DOI Creative Commons
Alexandre E. Nowill, Manuel Caruso, Pedro O. de Campos‐Lima

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: June 14, 2023

Humanity did surprisingly well so far, considering how unprepared it was to respond the coronavirus disease 2019 (COVID-19) threat. By blending old and ingenious new technology in context of accumulated knowledge on other human coronaviruses, several vaccine candidates were produced tested clinical trials record time. Today, five vaccines account for bulk more than 13 billion doses administered worldwide. The ability elicit biding neutralizing antibodies most often against spike protein is a major component protection conferred by immunization but alone not enough limit virus transmission. Thus, surge numbers infected individuals newer variants concern (VOCs) accompanied proportional increase severe death rate. This likely due antiviral T-cell responses, whose evasion difficult achieve. present review helps navigating very large literature T cell immunity induced acute respiratory syndrome 2 (SARS-CoV-2) infection vaccination. We examine successes shortcomings vaccinal light emergence VOCs with breakthrough potential. SARS-CoV-2 beings will coexist long while: be necessary update existing improve responses attain better COVID-19.

Language: Английский

The T-cell-directed vaccine BNT162b4 encoding conserved non-spike antigens protects animals from severe SARS-CoV-2 infection DOI Creative Commons

Christina M. Arieta,

Yushu Joy Xie,

Daniel Rothenberg

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(11), P. 2392 - 2409.e21

Published: April 13, 2023

T cell responses play an important role in protection against beta-coronavirus infections, including SARS-CoV-2, where they associate with decreased COVID-19 disease severity and duration. To enhance immunity across epitopes infrequently altered SARS-CoV-2 variants, we designed BNT162b4, mRNA vaccine component that is intended to be combined BNT162b2, the spike-protein-encoding vaccine. BNT162b4 encodes variant-conserved, immunogenic segments of nucleocapsid, membrane, ORF1ab proteins, targeting diverse HLA alleles. elicits polyfunctional CD4+ CD8+ animal models, alone or when co-administered BNT162b2 while preserving spike-specific immunity. Importantly, demonstrate protects hamsters from severe reduces viral titers following challenge variants. These data suggest a combination could reduce duration caused by circulating future currently being clinically evaluated BA.4/BA.5 Omicron-updated bivalent (NCT05541861).

Language: Английский

Citations

60
The Role of Memory T-Cell Mediated Immunity in Long-term COVID-19: Effects of Vaccination Status. DOI

Saulesh Kurmangaliyeva,

Akzhan M. Madenbayeva, Saltanat T. Urazayeva

et al.

PubMed, Journal Year: 2025, Volume and Issue: 50(2), P. 61 - 68

Published: Feb. 1, 2025

T-cell-mediated immunity is essential for controlling severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection, preventing disease, and potentially reducing the risk of long-term disease (COVID). This study investigated impact natural vaccination, hybrid on T-cell responses, with a particular emphasis role memory T-cells in COVID-19. The present reviewed current literature including development, individuals SARS-CoV-2 those vaccinated messenger RNA (mRNA) vaccines, immunity. It examined studies that compared activity, immune regulation, prevalence COVID-19 across these groups. Natural infection induces variable cases showing stronger but sometimes dysregulated immunological which may contribute to prolonged Vaccination, particularly mRNA elicits targeted consistent T-cells, severity, incidence Hybrid combines provides most robust protection, enhanceds reduces through balanced regulation. Memory play critical mitigating Vaccination significantly enhances immunity, minimizing chronic symptoms alone. effective defense, emphasizing importance even after prevent

Language: Английский

Citations

2
B-cell and antibody responses to SARS-CoV-2: infection, vaccination, and hybrid immunity DOI Creative Commons
Dennis Lapuente, Thomas Winkler, Matthias Tenbusch

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 21(2), P. 144 - 158

Published: Nov. 10, 2023

Abstract The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted scientific, medical, and biotech communities to investigate infection- vaccine-induced immune responses the context this pathogen. B-cell antibody are at center these investigations, as neutralizing antibodies (nAbs) an important correlate protection (COP) from infection primary target SARS-CoV-2 vaccine modalities. In addition absolute levels, nAb longevity, neutralization breadth, immunoglobulin isotype subtype composition, presence mucosal sites have become topics for scientists health policy makers. recent pandemic was still is a unique setting which study de novo memory (MBC) dynamic interplay immunity. It also provided opportunity explore new platforms, such mRNA or adenoviral vector vaccines, unprecedented cohort sizes. Combined with technological advances years, situation has detailed mechanistic insights into development but revealed some unexpected findings. review, we summarize key findings last 2.5 years regarding immunity, believe significant value not only future vaccination approaches endemic settings.

Language: Английский

Citations

37
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
The guided fire from within: intratumoral administration of mRNA-based vaccines to mobilize memory immunity and direct immune responses against pathogen to target solid tumors DOI Creative Commons
Renhao Li, Jingchu Hu, Rong Li

et al.

Cell Discovery, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 2, 2025

Abstract We investigated a novel cancer immunotherapy strategy that effectively suppresses tumor growth in multiple solid models and significantly extends the lifespan of tumor-bearing mice by introducing pathogen antigens into tumors via mRNA-lipid nanoparticles. The pre-existing immunity against antigen can enhance efficacy this approach. In previously immunized with BNT162b2, an mRNA-based COVID-19 vaccine encoding spike protein SARS-CoV-2 virus, intratumoral injections same efficiently tagged cells mRNA-expressed protein. This action rapidly mobilized memory to kill displaying protein, while concurrently reprogramming microenvironment (TME) attracting immune cells. partial elimination normalized TME further triggered extensive antigen-specific T cell responses through spreading, eventually resulting potent systemic tumor-targeting responses. Moreover, combining BNT162b2 treatment anti-PD-L1 therapy yielded more substantial therapeutic impact, even “cold tumor” types are typically less responsive treatment. Given majority global population has acquired various pathogens infection or vaccination, we believe that, addition utilizing widely held vaccine, mRNA vaccines other pathogens, such as Hepatitis B Virus (HBV), Common Human Coronaviruses (HCoVs), influenza could be transitioned clinical use holds great promise treating different cancer. selection expands opportunities may also overcome potential drug resistance.

Language: Английский

Citations

1
Role of antiviral CD8+ T cell immunity to SARS-CoV-2 infection and vaccination DOI Creative Commons
Vivien Karl, Maike Hofmann, Robert Thimme

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

ABSTRACT The COVID-19 pandemic has greatly enhanced our understanding of CD8+ T cell immunity and their role in natural infection vaccine-induced protection. Rapid early SARS-CoV-2-specific responses have been associated with efficient viral clearance mild disease. Virus-specific can compensate for waning, morbidity-related, iatrogenic reduction humoral immunity. After or vaccination, memory cells are formed, which mount an recall response the event breakthrough help to protect from severe Due breadth ability target mainly highly conserved epitopes, also able cross-recognize epitopes variants, thus maintaining even after emergence evolution. In some cases, however, may contribute pathogenesis COVID-19. particular, delayed uncontrolled, e.g., nonspecific hyperactivated, cytotoxic linked poor outcomes. this minireview, we summarize tremendous knowledge about SARS-CoV-2 vaccination that gained over past 5 years, while highlighting critical gaps remain.

Language: Английский

Citations

1
Can the Revolution in mRNA-Based Vaccine Technologies Solve the Intractable Health Issues of Current Ruminant Production Systems? DOI Creative Commons
Timothy J. Mahony, Tatiana Briody, Sheila C. Ommeh

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 152 - 152

Published: Jan. 31, 2024

To achieve the World Health Organization's global Sustainable Development Goals, increased production of high-quality protein for human consumption is required while minimizing, ideally reducing, environmental impacts. One way to these goals address losses within current livestock systems. Infectious diseases are key limiters edible production, affecting both quantity and quality. In addition, some zoonotic threats potential contributors emergence antimicrobial resistance. Vaccination has proven be highly successful in controlling even eliminating several economic importance. However, many diseases, existing emerging, have recalcitrant targets conventional vaccination technologies. The threat posed by COVID-19 pandemic resulted unprecedented investment vaccine technologies accelerate development safe efficacious vaccines. While platforms emerged as front runners meet this challenge, clear winner mRNA-based vaccination. challenge now industries relevant stakeholders harness rapid advances production. This review examines features mRNA vaccines, technology control infectious importance that otherwise difficult using approaches. focuses on challenging ruminants due their Overall, literature suggests that, vaccines challenges veterinary medicine, further developments likely promise realized ruminant other species.

Language: Английский

Citations

6
Nanoplatform Based Intranasal Vaccines: Current Progress and Clinical Challenges DOI Creative Commons
Ziyi Bai,

Dandan Wan,

Tianxia Lan

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(36), P. 24650 - 24681

Published: Aug. 26, 2024

Multiple vaccine platforms have been employed to develop the nasal SARS-CoV-2 vaccines in preclinical studies, and dominating pipelines are viral vectored as protein-based vaccines. Among them, several vectored-based entered clinical development. Nevertheless, some unsatisfactory results were reported these studies. In face of such urgent situations, it is imperative rapidly next-generation intranasal COVID-19 utilizing other technologies. Nanobased emerged an approach against respiratory infectious diseases. Harnessing power nanotechnology, offer a noninvasive yet potent defense pathogens, including threat COVID-19. The improvements made mucosal delivery technologies based on nanoparticles, lipid polymeric inorganic nanoparticles etc., not only provide stability controlled release but also enhance adhesion, effectively overcoming limitations conventional Hence, this review, we overview evaluation highlight current barriers. Next, modern systems nanoplatforms summarized. challenges application nanoplatform finally discussed.

Language: Английский

Citations

6
Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine DOI Creative Commons
Shanhe Yu,

Yingni Lin,

Yong Li

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(21), P. 4615 - 4631.e16

Published: Sept. 27, 2023

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in booster-dependent manner. Yet, the underlying mechanisms remain unclear. During 2022 outbreak Shanghai, we enrolled 122 infected adults 50 uninfected controls who had been unvaccinated or vaccinated with two three doses of COVID-19 inactive vaccines performed integrative analysis 41-plex CyTOF, RNA-seq, Olink on their peripheral blood samples. The frequencies HLA-DRhi classical monocytes, non-classical Th1-like Tem tended to increase, whereas frequency Treg was reduced by booster vaccine, they influenced occurrence vaccine dose-dependent Intercorrelation mechanistic suggested that induced monocytic training, which would prime activation maturation rather than differentiating into myeloid-derived suppressive cells upon infections. Overall, our study provides insights how elaborates immunity across variants.

Language: Английский

Citations

15
Seeing the T cell Immunity of SARS-CoV-2 and SARS-CoV: Believing the Epitope-Oriented Vaccines DOI Creative Commons

Can Yue,

Pengyan Wang,

Jinmin Tian

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(13), P. 4052 - 4060

Published: Jan. 1, 2023

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end 2019 stimulated vigorous research efforts in immunology and vaccinology.In addition to innate immune responses, both virus-specific humoral cellular responses are importance for viral clearance.T cell epitopes play a central role T cell-based responses.Herein, we summarized peptide/major histocompatibility complex (pMHC) structures SARS-CoV-2-derived available Protein Data Bank (PDB) proposed challenge opportunities using future vaccine development efforts.A total 27 SARS-CoV-2 related pMHC five complexes with receptors were retrieved.The peptides mainly distributed on spike (S), nucleocapsid (N), ORF1ab proteins.Most conserved among variants concerns (VOCs) SARS-CoV-2, except several mutated located S protein.The human leukocyte antigen (HLA) complexed seven derived from SARS-CoV also retrieved, which showed potential cross immunity SARS-CoV-2.Structural studies antigenic help visualize processes mechanisms immunity.T epitope-oriented vaccines next-generation worthy further investigation.

Language: Английский

Citations

11