A Highly Conserved Peptide Vaccine Candidate Activates Both Humoral and Cellular Immunity Against SARS-CoV-2 Variant Strains

Facing the imminent need for vaccine candidates with cross-protection against globally circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we present a conserved antigenic peptide RBD9.1 with both T-cell and B-cell epitopes. RBD9.1 can be recognized by coronavirus disease 2019 (COVID-19) convalescent serum, particularly for those with high neutralizing potency. Immunization with RBD9.1 can successfully induce the production of the receptor-binding domain (RBD)-specific antibodies in Balb/c mice. Importantly, the immunized sera exhibit sustained neutralizing efficacy against multiple dominant SARS-CoV-2 variant strains, including B.1.617.2 that carries a point mutation (SL452R) within the sequence of RBD9.1. Specifically, SY451 and SY454 are identified as the key amino acids for the binding of the induced RBD-specific antibodies to RBD9.1. Furthermore, we have confirmed that the RBD9.1 antigenic peptide can induce a S448-456 (NYNYLYRLF)-specific CD8+ T-cell response. Both RBD9.1-specific B cells and the S448-456-specific T cells can still be activated more than 3 months post the last immunization. This study provides a potential vaccine candidate that can generate long-term protective efficacy over SARS-CoV-2 variants, with the unique functional mechanism of activating both humoral and cellular immunity.

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Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

10.1101/2021.09.21.461301 ◽

2021 ◽

Author(s):

Simone Parn ◽

Gabriel Jabbour ◽

Vincent Nguyenkhoa ◽

Sivanesan Dakshanamurthy

Keyword(s):

T Cell ◽

Vaccine Development ◽

Human Life ◽

Peptide Vaccine ◽

T Cell Response ◽

Cd4 T Cell ◽

World Population ◽

T Cell Epitopes ◽

The World ◽

Potential Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has challenged public health at an unprecedented scale which has led to a dramatic loss of human life worldwide. To design a protective vaccine against SARS-CoV-2, it is necessary to understand which SARS-CoV-2 specific epitopes can elicit a T cell response and provide protection across a broad population. In this study, PLpro and RdRp, two immunogenic non-structural proteins from an immunodominant gene region ORF1ab, as well as ORF3a and ORF9b are identified as potential vaccine targets against SARS-CoV-2. To select top epitopes for vaccine design, we used various clinical properties, such as antigenicity, allergenicity, toxicity and IFN-y secretion. The analysis of CD8 and CD4 T cell epitopes revealed multiple potential vaccine constructs that cover a high percentage of the world population. We identified 8 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 proteins for nsp3, 4 for nsp12, 11 for ORF3a and 3 for ORF9b that are common across four lineages of variants of concern: B.1.1.7, P.1, B.1.351 and B.1.617.2, which protect 98.12%, 87.08%, 96.07% and 63.8% of the world population, respectively. We also identified variant specific T cell epitopes that could be useful in targeting each variant strain separately. Including the prediction of mouse MHC affinity towards our top CD8 epitopes, our study revealed a total of 3 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 epitopes overlapping with 6 antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD4 epitopes across all four variants of concern which can effectively be utilized in pre-clinical studies. The landscape of SARS-CoV-2 T cell epitopes that we identified can help lead SARS-CoV-2 vaccine development as well as epitope-based peptide vaccine research in the future.

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Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response

The Journal of Immunology ◽

10.4049/jimmunol.1700467 ◽

2018 ◽

Vol 200 (10) ◽

pp. 3464-3474 ◽

Cited By ~ 8

Author(s):

Hiep Khong ◽

Annika Volmari ◽

Meenu Sharma ◽

Zhimin Dai ◽

Chinonye S. Imo ◽

...

Keyword(s):

T Cell ◽

Antigen Presentation ◽

Cell Response ◽

Peptide Vaccine ◽

Cd8 T Cell ◽

T Cell Response ◽

Vaccine Formulation

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Pretransplant BK virus-specific T-cell-mediated immunity and serotype specific antibodies may have utility in identifying patients at risk for BK virus associated haemorrhagic cystitis after allogeneic HSCT

10.1101/2021.06.09.21258555 ◽

2021 ◽

Author(s):

Marketa Stastna-Markova ◽

Eva Hamsikova ◽

Petr Hainz ◽

Petr Hubacek ◽

Marie Kroutilova ◽

...

Keyword(s):

At Risk ◽

T Cell ◽

Cell Response ◽

Bk Virus ◽

T Cell Response ◽

Cell Mediated Immunity ◽

Haemorrhagic Cystitis ◽

Hematopoietic Stem ◽

Specific Antibodies ◽

Clinical Risk

BK polyomavirus (BKV) persists lifelong in the urinary tract with asymptomatic urinary shedding in healthy individuals. In immunocompromised persons after transplantation of hematopoietic stem cells (HSCT) the BKV high-rate replication is associated with haemorrhagic cystitis (HC) with a reported incidence of 17 %. Numerous studies of reconstitution of the immune system after HSCT have established the principal role of T cell effectors in the control of viral replication and reactivation. The value of pretransplant BKV-specific antibodies in transplanted patients for the protection from viral disease was long considered insignificant. We hypothesized that the status of BKV immunity prior to HSCT could provide evidence for the BKV tendency to reactivate and that examining the level of subtype-specific antibodies and T-cell response in individual patients could help to predict the risk of BKV reactivation and HC. Evaluation of the risk of HC in relation to pretransplant anti-BKV1,2,4 IgG levels together with clinical factors known before transplantation revealed that patients with medium anti-BKV IgG and significant clinical risk (SR) have a very significantly increased HC risk in comparison with the reference group of low anti-BKV IgG level and low clinical risk (LR) (P=0.0009). Analysis of pretransplant T cell immunity to BKV antigens VP1 and LTag has shown that magnitude of IFN-gamma T cell response inversely corelated with posttransplant DNAuria. We hypothesize that the control of BKV latency by BKV specific T cells before HSCT would be one of the factors that influence BKV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of patients who are at risk of developing BKV disease after HSCT.

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Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach

Briefings in Bioinformatics ◽

10.1093/bib/bbaa340 ◽

2020 ◽

Author(s):

Aftab Alam ◽

Arbaaz Khan ◽

Nikhat Imam ◽

Mohd Faizan Siddiqui ◽

Mohd Waseem ◽

...

Keyword(s):

T Cell ◽

Vaccine Development ◽

Peptide Vaccine ◽

Specific Treatment ◽

T Cell Response ◽

Surface Glycoprotein ◽

Antigenic Peptides ◽

Population Coverage ◽

Geographical Regions ◽

Cluster Of Differentiation

Abstract The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

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Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

Journal of Virology ◽

10.1128/jvi.74.17.8094-8101.2000 ◽

2000 ◽

Vol 74 (17) ◽

pp. 8094-8101 ◽

Cited By ~ 77

Author(s):

Robbert G. van der Most ◽

Kaja Murali-Krishna ◽

Rafi Ahmed ◽

James H. Strauss

Keyword(s):

T Cells ◽

T Cell ◽

Dengue Virus ◽

Yellow Fever ◽

Cd8 T Cells ◽

Cell Response ◽

Protective Efficacy ◽

Cd8 T Cell ◽

T Cell Response ◽

E Proteins

ABSTRACT We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

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A Candida albicans Mannoprotein Deprived of Its Mannan Moiety Is Efficiently Taken Up and Processed by Human Dendritic Cells and Induces T-Cell Activation without Stimulating Proinflammatory Cytokine Production

Infection and Immunity ◽

10.1128/iai.00669-08 ◽

2008 ◽

Vol 76 (9) ◽

pp. 4359-4367 ◽

Cited By ~ 21

Author(s):

Donatella Pietrella ◽

Patrizia Lupo ◽

Anna Rachini ◽

Silvia Sandini ◽

Alessandra Ciervo ◽

...

Keyword(s):

Dendritic Cells ◽

Candida Albicans ◽

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Vaccine Candidate ◽

Pathogenic Fungi ◽

T Cell Response ◽

Necrosis Factor Alpha ◽

Recombinant Product

ABSTRACT Mannoproteins are cell wall components of pathogenic fungi and play major virulence and immunogenic roles with both their mannan and protein moieties. The 65-kDa mannoprotein (MP65) of Candida albicans is a β-glucanase adhesin recognized as a major target of the human immune response against this fungus, and its recombinant product (rMP65; devoid of the mannan moiety) is presently under consideration as a vaccine candidate. Here we investigated cellular and molecular aspects of the interaction of rMP65 with human antigen-presenting cells. We also assessed the ability of rMP65 to initiate a T-cell response. Both the native mannosylated MP65 (nMP65) and the recombinant product were efficiently bound and taken up by macrophages and dendritic cells. However, contrarily to nMP65, rMP65 did not induce tumor necrosis factor alpha and interleukin-6 release from these cells. On the other hand, rMP65 was rapidly endocytosed by both macrophages and dendritic cells, in a process involving both clathrin-dependent and clathrin-independent mechanisms. Moreover, the RGD sequence inhibited rMP65 uptake to some extent. After internalization, rMP65 partially colocalized with lysosomal membrane-associated glycoproteins 1 and 2. This possibly resulted in efficient protein degradation and presentation to CD4+ T cells, which proliferated and produced gamma interferon. Collectively, these results demonstrate that the absence of the mannan moiety does not deprive MP65 of the capacity to initiate the pattern of cellular and molecular events leading to antigen presentation and T-cell activation, which are essential features for further consideration of MP65 as a potential vaccine candidate.

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Preexisting Inflammation Due to Mycobacterium bovis BCG Infection Differentially Modulates T-Cell Priming against a Replicating or Nonreplicating Immunogen

Infection and Immunity ◽

10.1128/iai.70.4.1957-1964.2002 ◽

2002 ◽

Vol 70 (4) ◽

pp. 1957-1964 ◽

Cited By ~ 15

Author(s):

Renu Dudani ◽

Yvan Chapdelaine ◽

Henk van Faassen ◽

Dean K. Smith ◽

Hao Shen ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mycobacterium Bovis ◽

Inflammatory Responses ◽

Protective Efficacy ◽

T Cell Response ◽

Boost Vaccine ◽

Ifn Γ ◽

T Cell Priming

ABSTRACT Induction of T-cell memory by vaccination ensures long-term protection against pathogens. We determined whether on-going inflammatory responses during vaccination influenced T-cell priming. A preexposure of mice to Mycobacterium bovis BCG impaired their subsequent ability to prime T cells against Listeria monocytogenes. This was characterized by a decrease in L. monocytogenes-specific gamma interferon (IFN-γ)-secreting CD4+ and CD8+ T cells. The intensity of T-cell priming towards L. monocytogenes depended on the extent of L. monocytogenes expansion, and a cessation of this expansion caused by M. bovis BCG-induced inflammation resulted in impairment in T-cell priming. A challenge of M. bovis BCG-infected mice with a higher L. monocytogenes dose increased L. monocytogenes survival and restored T-cell priming towards L. monocytogenes. Impairment in T-cell priming towards L. monocytogenes due to M. bovis BCG-induced inflammation resulted in a compromised protective efficacy in the long term after mice were rechallenged with L. monocytogenes. Preexisting inflammation selectively impaired T-cell priming for replicating immunogens as CD8+ T-cell response to ovalbumin administered as an inert antigen (ovalbumin-archaeosomes) was enhanced by M. bovis BCG preimmunization, whereas priming towards ovalbumin administered as a live immunogen (L. monocytogenes-ovalbumin) was impaired. Thus, depending on the nature of the immunogen, the presence of prior inflammatory responses may either impede or boost vaccine efficacy.

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Induction of a Robust Humoral Response using HIV-1 VLPMPER-V3 as a Novel Candidate Vaccine in BALB/c Mice

Current HIV Research ◽

10.2174/1570162x17666190306124218 ◽

2019 ◽

Vol 17 (1) ◽

pp. 33-41 ◽

Cited By ~ 3

Author(s):

Fatemeh Tohidi ◽

Seyed Mehdi Sadat ◽

Azam Bolhassani ◽

Ramin Yaghobi ◽

Mona Sadat Larijani

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Humoral Response ◽

Cellular Responses ◽

Immunodeficiency Virus ◽

Potential Vaccine ◽

Humoral Responses ◽

Hiv 1

Background: Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. Objective: This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. Methods: Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. Results: The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. Conclusion: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.

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Immunological Memory: Remembering Our Pathogens.

Blood ◽

10.1182/blood.v112.11.sci-23.sci-23 ◽

2008 ◽

Vol 112 (11) ◽

pp. sci-23-sci-23

Author(s):

Rafi Ahmed

Keyword(s):

T Cells ◽

T Cell ◽

B Cell ◽

Viral Infections ◽

Memory T Cells ◽

Immunological Memory ◽

T Cell Response ◽

Cell Memory ◽

Humoral And Cellular Immunity ◽

B Cell Memory

Abstract Acute viral infections induce long-term humoral and cellular immunity. However, the nature of T- and B-cell memory is different. Antiviral B-cell memory is usually manifested by continuous antibody production that lasts for many years after infection or vaccination. In contrast, the effector phase of the T cell response is short-lived (a few weeks), and “memory” in the T-cell compartment results from the presence of memory T cells, which are found at higher frequencies and can respond faster and develop into effector cells (i.e., CTL or cytokine producers) more efficiently than can naïve T cells. In this talk, I will discuss the following aspects of immunological memory: Functional differences between naïve and memory T cells; Memory T cell differentiation and memory cell subsets; and Protective immunity by memory CD8 T cells.

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Computational study on the origin of the cancer immunotherapeutic potential of B and T cell epitope peptides

Molecular BioSystems ◽

10.1039/c7mb00219j ◽

2017 ◽

Vol 13 (11) ◽

pp. 2310-2322 ◽

Cited By ~ 1

Author(s):

Hao Li ◽

Nalini Schaduangrat ◽

Saw Simeon ◽

Chanin Nantasenamat

Keyword(s):

T Cell ◽

Cellular Immunity ◽

Computational Analysis ◽

Computational Study ◽

Cell Epitope ◽

T Cell Epitope ◽

Humoral And Cellular Immunity ◽

Dual Response ◽

Cancer Immunotherapeutic

Computational analysis of anticancer humoral and cellular immunity activating dual response epitope peptides reveals significant differences to mono-response activating peptides.

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