Next-Generation Vaccines against COVID-19 Variants: Beyond the Spike Protein DOI Creative Commons
Srinivasa Reddy Bonam, Haitao Hu

Zoonoses, Journal Year: 2023, Volume and Issue: 3(1)

Published: Jan. 1, 2023

Vaccines are among the most effective medical countermeasures against infectious diseases. The current Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spurred scientific strategies to fight disease. Since 2020, a great number of vaccines based on different platforms have been in development response which mRNA, adenoviral vector, and subunit clinically approved for use humans. These first-generation COVID-19 largely target viral spike (S) protein aim eliciting potent neutralizing antibodies. With emergence SARS-CoV-2 variants, especially highly transmissible Omicron strains, S-based vaccine faced constant challenges due strong immune escape variants. nucleocapsid (N) is one proteins that induces T-cell immunity more conserved across Inclusion N reported. Here, we briefly reviewed discussed disease, strategies, focused immunobiology host immunity, as well next-generation involving protein, combat emerging

Language: Английский

The SARS-CoV-2 nucleocapsid protein: its role in the viral life cycle, structure and functions, and use as a potential target in the development of vaccines and diagnostics DOI Creative Commons
Wenbing Wu, Ying Cheng, Hong Zhou

et al.

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Jan. 10, 2023

Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort develop diagnostic technologies for detecting positive infections within shortest possible time, vaccines drugs specifically prevention treatment of COVID-19 disease. At same emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in coronavirus life cycle, participates various vital activities after virus invasion. It has attracted large amount attention drug development. Here, we summarize latest research N protein, including its structure function, post-translational modifications addition involvement liquid-liquid phase separation (LLPS) use as basis development techniques.

Language: Английский

Citations

146
SARS-CoV-2 viral clearance and evolution varies by type and severity of immunodeficiency DOI Open Access
Yijia Li, Manish C. Choudhary, James Regan

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(731)

Published: Jan. 24, 2024

Despite vaccination and antiviral therapies, immunocompromised individuals are at risk for prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but the immune defects that predispose an individual to persistent disease 2019 (COVID-19) remain incompletely understood. In this study, we performed detailed viro-immunologic analyses of a prospective cohort participants with COVID-19. The median times nasal viral RNA culture clearance in immunosuppression due hematologic malignancy or transplant (S-HT) were 72 40 days, respectively, both which significantly longer than rates autoimmunity B cell deficiency (S-A), nonsevere immunodeficiency, nonimmunocompromised groups ( P < 0.01). Participants who severely had greater SARS-CoV-2 evolution higher developing resistance against therapeutic monoclonal antibodies. Both S-HT S-A diminished SARS-CoV-2–specific humoral responses, whereas only group reduced T cell–mediated responses. This highlights varied COVID-19 across distinct immunosuppressive conditions suggests suppression responses results highest contributing infection.

Language: Английский

Citations

61
Pre-existing immunity modulates responses to mRNA boosters DOI Creative Commons
Tanushree Dangi, Sarah Sanchez, Min Han Lew

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(3), P. 112167 - 112167

Published: Feb. 15, 2023

mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although boosters being implemented, extent to which pre-existing influences efficacy remains unclear. In a cohort individuals primed with mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost associated higher fold-increase after boost, suggesting modulates immunogenicity vaccines. Our studies mice show antibodies accelerate clearance vaccine antigen via Fc-dependent mechanisms, limiting amount available prime B cell responses These data demonstrate "tug war" between de novo following vaccination, they suggest transient downmodulation effector function may improve

Language: Английский

Citations

36
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
Treatments for COVID-19 DOI
Hayden S Andrews, Jonathan D. Herman, Rajesh T. Gandhi

et al.

Annual Review of Medicine, Journal Year: 2023, Volume and Issue: 75(1), P. 145 - 157

Published: Sept. 19, 2023

The treatment for COVID-19 has evolved rapidly since the start of pandemic and now consists mainly antiviral immunomodulatory agents. Antivirals, such as remdesivir nirmatrelvir-ritonavir, have proved to be most useful earlier in illness (e.g., outpatient therapy) less severe disease. Immunomodulatory therapies, dexamethasone interleukin-6 or Janus kinase inhibitors, are disease critical illness. role anti-SARS-CoV-2 monoclonal antibodies diminished because emergence viral variants that not anticipated susceptible these treatments, there still is a consensus on use convalescent plasma. been associated with increased rates venous thromboembolism, but antithrombotic therapy limited. Multiple investigational agents continue studied, which will alter current paradigms new data released.

Language: Английский

Citations

31
Protective mechanisms of nonneutralizing antiviral antibodies DOI Creative Commons
T.L. Chandler,

Agnes Yang,

Claire E. Otero

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(10), P. e1011670 - e1011670

Published: Oct. 5, 2023

Antibodies that can bind to viruses but are unable block infection in cell culture known as "nonneutralizing antibodies." Such antibodies nearly universally elicited following viral and have been characterized infections such influenza, rotavirus, cytomegalovirus, HIV, SARS-CoV-2. It has widely assumed these nonneutralizing do not function a protective way vivo therefore desirable targets of antiviral interventions; however, increasing evidence now shows this be true. Several virus-specific antibody responses correlated with protection human studies also shown significantly reduce virus replication animal models. The mechanisms by which many is only coming light. While cannot prevent entering their host cell, work the extracellular space recruit effector proteins or cells destroy antibody-virus complex. Other exert effects inside cells, either blocking life cycle directly recruiting intracellular Fc receptor TRIM21. In review, we will discuss multitude ways against range infections.

Language: Английский

Citations

30
OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model DOI Creative Commons
Charlotte Primard, Élodie Monchâtre-Leroy, Judith del Campo

et al.

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

Published: June 19, 2023

Spike-based COVID-19 vaccines induce potent neutralizing antibodies but their efficacy against SARS-CoV-2 variants decreases. OVX033 is a recombinant protein composed of the full-length nucleocapsid (N) genetically fused to oligoDOM ® , self-assembling domain which improves antigen immunogenicity. including N as an antigenic target proposed new vaccine candidate providing broad-spectrum protection sarbecoviruses. demonstrated its ability trigger cross-reactive T cell responses and cross-protection three (B.1 Europe, Delta B.1.617.2, Omicron B.1.1.529) in hamster challenge model, evidenced by lower weight loss, lung viral loads, reduced histopathological lesions.

Language: Английский

Citations

24
Combined anti-S1 and anti-S2 antibodies from hybrid immunity elicit potent cross-variant ADCC against SARS-CoV-2 DOI Creative Commons
Michael D. Grant, Kirsten Bentley, Ceri A. Fielding

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(15)

Published: June 20, 2023

Antibodies capable of neutralising SARS-CoV-2 are well studied, but Fc receptor-dependent antibody activities that can also significantly impact the course infection have not been studied in such depth. As most vaccines induce only anti-spike antibodies, here we investigated spike-specific antibody-dependent cellular cytotoxicity (ADCC). Vaccination produced antibodies weakly induced ADCC, however, from individuals who were infected prior to vaccination ('hybrid' immunity) elicited strong ADCC. Quantitative and qualitative aspects humoral immunity contributed this capability, with skewing IgG production towards S2, S1 hybrid evoking responses against both domains. targeting spike domains support NK cell activation, three regions reactivity outside receptor-binding domain (RBD) corresponding potent Consequently, ADCC by ancestral antigen was conserved variants containing neutralisation escape mutations RBD. Induction recognising a broad range epitopes eliciting durable may partially explain why provides superior protection disease than alone, demonstrates spike-only subunit would benefit strategies combined anti-S1 S2 responses.

Language: Английский

Citations

16
Immunogenicity, safety, and preliminary efficacy evaluation of OVX836, a nucleoprotein-based universal influenza A vaccine candidate: a randomised, double-blind, placebo-controlled, phase 2a trial DOI
Isabel Leroux‐Roels, Paul Willems, Gwenn Waerlop

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(12), P. 1360 - 1369

Published: July 27, 2023

Language: Английский

Citations

16
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