Comparative Antigenicity and Immunogenicity of Hepadnavirus Core Proteins

ABSTRACT The hepatitis B virus core protein (HBcAg) is a uniquely immunogenic particulate antigen and as such has been used as a vaccine carrier platform. The use of other hepadnavirus core proteins as vaccine carriers has not been explored. To determine whether the rodent hepadnavirus core proteins derived from the woodchuck (WHcAg), ground squirrel (GScAg), and arctic squirrel (AScAg) viruses possess immunogen characteristics similar to those of HBcAg, comparative antigenicity and immunogenicity studies were performed. The results indicate that (i) the rodent core proteins are equal in immunogenicity to or more immunogenic than HBcAg at the B-cell and T-cell levels; (ii) major histocompatibility complex (MHC) genes influence the immune response to the rodent core proteins (however, nonresponder haplotypes were not identified); (iii) WHcAg can behave as a T-cell-independent antigen in athymic mice; (iv) the rodent core proteins are not significantly cross-reactive with the HBcAg at the antibody level (however, the nonparticulate “eAgs” do appear to be cross-reactive); (v) the rodent core proteins are only partially cross-reactive with HBcAg at the CD4+ T-cell level, depending on MHC haplotype; and (vi) the rodent core proteins are competent to function as vaccine carrier platforms for heterologous, B-cell epitopes. These results have implications for the selection of an optimal hepadnavirus core protein for vaccine design, especially in view of the “preexisting” immunity problem that is inherent in the use of HBcAg for human vaccine development.

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Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-21444-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Adam K. Wheatley ◽

Jennifer A. Juno ◽

Jing J. Wang ◽

Kevin J. Selva ◽

Arnold Reynaldi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Natural Infection ◽

Population Level ◽

Cell Dynamics ◽

Follicular Helper ◽

Cell Immunity ◽

Specific Igg ◽

Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

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The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+Oscillations

Journal of Biological Chemistry ◽

10.1074/jbc.m300185200 ◽

2003 ◽

Vol 278 (21) ◽

pp. 18877-18883 ◽

Cited By ~ 44

Author(s):

Anders Bergqvist ◽

Sara Sundström ◽

Lina Y. Dimberg ◽

Erik Gylfe ◽

Maria G. Masucci

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

T Cell ◽

T Cell Receptor ◽

Core Protein ◽

T Cell Responses ◽

Cell Receptor ◽

Cell Responses ◽

Virus Core

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In-silico Design of Multi-epitope Vaccine against Nipah Virus using Immunoinformatics Approach

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.15.1.16 ◽

2021 ◽

Vol 15 (1) ◽

pp. 212-231

Author(s):

Suraj Raju ◽

Debasish Sahoo ◽

Vikas Kumar Bhari

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Vaccine Development ◽

Homology Modelling ◽

Nipah Virus ◽

Docking Simulation ◽

Dynamics Simulation ◽

Cytotoxic T Cell ◽

Viral Spread

Nipah virus is a pleomorphic virus that causes high mortality with unpredictable outbreaks. The virus also shows high zoonotic potential with long term neurological damage after recovery further adding to the disease burden. An in-silico epitope-based vaccine offers a promising solution to supplement wider efforts to control the viral spread. This is achieved through immunoinformatics approach using a plethora of servers available. We derived cytotoxic T-cell, T-Helper, B-cell and IFN-γ targeting epitopes from surface glycoprotein G. Cytotoxic T-cell specific epitopes, HLA-B*4402, chimeric multiepitope vaccine structures were prepared using homology modelling method. The structures were validated using various methods and docking simulation was performed between epitopes and HLA-B*4402. Similarly, the vaccine construct was docked to Toll like receptor-4 and a molecular dynamics simulation was performed to assess stability of interaction. Both the docking simulations showed stable interactions with their respective receptors. Immune-simulation was carried out to validate the efficacy of vaccine candidate which showed elevated levels of antibodies such as IgM and IgG due to increase in active B cell population. Both in-vitro and in-vivo serological analysis is required for confirmation of vaccine potency. To facilitate this effort, codon optimization was undertaken to remove existing codon bias. The optimized gene sequence was cloned into the PUC19 vector to express in Escherichia coli K12 strain. Additionally, a poly histidine (6xHis) tag was added at the C-terminal end to ease the purification step. The immune-informatics approach hopes to accelerate vaccine development process to reduce the risk of attenuation while increasing the success rates of pre-clinical trials.

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Designing multiepitope-based vaccine against Eimeria from immune mapped protein 1 (IMP-1) antigen using immunoinformatic approach

Scientific Reports ◽

10.1038/s41598-021-97880-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Thabile Madlala ◽

Victoria T. Adeleke ◽

Abiodun J. Fatoba ◽

Moses Okpeku ◽

Adebayo A. Adeniyi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Cell Epitope ◽

Docking Simulation ◽

Cost Effective ◽

Economic Loss ◽

T Cell Epitopes ◽

Live Vaccines ◽

Physiochemical Parameters

AbstractDrug resistance against coccidiosis has posed a significant threat to chicken welfare and productivity worldwide, putting daunting pressure on the poultry industry to reduce the use of chemoprophylactic drugs and live vaccines in poultry to treat intestinal diseases. Chicken coccidiosis, caused by an apicomplexan parasite of Eimeria spp., is a significant challenge worldwide. Due to the experience of economic loss in production and prevention of the disease, development of cost-effective vaccines or drugs that can stimulate defence against multiple Eimeria species is imperative to control coccidiosis. This study explored Eimeria immune mapped protein-1 (IMP-1) to develop a multiepitope-based vaccine against coccidiosis by identifying antigenic T-cell and B-cell epitope candidates through immunoinformatic techniques. This resulted in the design of 7 CD8+, 21 CD4+ T-cell epitopes and 6 B-cell epitopes, connected using AAY, GPGPG and KK linkers to form a vaccine construct. A Cholera Toxin B (CTB) adjuvant was attached to the N-terminal of the multiepitope construct to improve the immunogenicity of the vaccine. The designed vaccine was assessed for immunogenicity (8.59968), allergenicity and physiochemical parameters, which revealed the construct molecular weight of 73.25 kDa, theoretical pI of 8.23 and instability index of 33.40. Molecular docking simulation of vaccine with TLR-5 with binding affinity of − 151.893 kcal/mol revealed good structural interaction and stability of protein structure of vaccine construct. The designed vaccine predicts the induction of immunity and boosted host's immune system through production of antibodies and cytokines, vital in hindering surface entry of parasites into host. This is a very important step in vaccine development though further experimental study is still required to validate these results.

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Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome

10.1101/2020.05.14.093757 ◽

2020 ◽

Author(s):

Stephen N. Crooke ◽

Inna G. Ovsyannikova ◽

Richard B. Kennedy ◽

Gregory A. Poland

Keyword(s):

T Cell ◽

B Cell ◽

Selection Criteria ◽

Vaccine Development ◽

Hla Class I ◽

Class Ii ◽

Class I ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Novel Coronavirus

AbstractA novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.Significance StatementThe novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the proteins targeted by the immune response remains relatively limited, making it difficult to rationally design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen.

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Computational Prediction of Usutu Virus E Protein B Cell and T Cell Epitopes for Potential Vaccine Development

Scandinavian Journal of Immunology ◽

10.1111/sji.12544 ◽

2017 ◽

Vol 85 (5) ◽

pp. 350-364 ◽

Cited By ~ 3

Author(s):

N. Palanisamy ◽

J. Lennerstrand

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Computational Prediction ◽

T Cell Epitopes ◽

Usutu Virus ◽

E Protein ◽

Potential Vaccine ◽

Protein B

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Activation of Refractory T Cell Responses against Hepatitis C Virus Core Protein by Ablation of Interfering Hydrophobic Domains

Molecular Therapy ◽

10.1016/j.ymthe.2005.09.005 ◽

2006 ◽

Vol 13 (2) ◽

pp. 338-346 ◽

Cited By ~ 5

Author(s):

Helen A. Andersson ◽

Rana A.K. Singh ◽

Michael A. Barry

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

T Cell ◽

Core Protein ◽

T Cell Responses ◽

Cell Responses ◽

Virus Core

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Semliki forest virus core protein fragmentation: Its possible role in nucleocapsid disassembly

Bioscience Reports ◽

10.1007/bf01150478 ◽

1993 ◽

Vol 13 (6) ◽

pp. 333-347 ◽

Cited By ~ 5

Author(s):

Andreas Schlegel ◽

Johann Schaller ◽

Pia Jentsch ◽

Christoph Kempf

Keyword(s):

Capsid Protein ◽

Semliki Forest Virus ◽

Core Protein ◽

Gradient Centrifugation ◽

Biological Significance ◽

Acidic Ph ◽

Virus Particles ◽

Virus Core ◽

Core Proteins ◽

Protein Fragmentation

Semliki Forest virus (SFV) envelope proteins function as proton pores under mildly acidic conditions and translocate protons across the viral membrane [Schlegel, A., Omar, A., Jentsch, P., Morell, A. and Kemp, F. C. (1991) Biosci. Rep. 11, 243–255]. As a consequence, during uptake of SFV by cells via receptor-mediated endocytosis the nucleocapsid is supposed to be exposed to protons. In this paper the effects of mildly acidic pH on SFV nucleocapsids were examined. A partial proteolytic fragmentation of core proteins was observed when nucleocapsids were exposed to mildly acidic pH. A similar proteolytic event was detected when intact SFV virions were exposed to identical conditions. Protease protection assays with exogenous bromelain provided evidence that the capsid protein degradation was due to an endogenous proteolytic activity and not to a proteolytic contamination. Detergent solubilization of virus particles containing degraded nucleocapsids followed by sucrose gradient centrifugation led to a separation of capsid protein fragments and remaining nucleocapsids. These data are discussed in terms of a putative biological significance, namely that the core protein fragmentation may play a role in nucleocapsid disassembly.

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