Special Issue "Immunity, Immunoprevention and Immunotherapy in Cancer and Viral Diseases"

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Clinical Immunology".

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Dr. Tahseen H. Nasti
E-Mail Website
Guest Editor
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA
Interests: cancer and antiviral immunotherapy; radiation-mediated immune responses against cancer; immune responses to viral infections
Dr. Christiane Eberhardt
E-Mail Website
Guest Editor
Centre for Vaccinology, University Hospitals of Geneva, Geneva, Switzerland and Emory Vaccine Center, Emory University, Atlanta, GA, USA
Interests: immune responses to cancer; viral infections and vaccinations

Special Issue Information

Dear Colleagues,

The mechanisms involved in innate and adaptive immune responses that promote or inhibit tumor progression are well described. Similarly, in viral infections, these responses either eliminate the virus after infection or intrinsic and extrinsic factors lead to chronic disease. Persistent antigen stimulation and severe inflammation in chronic viral infections or cancer result in T cell exhaustion and dysfunction, which in part contributes to severe disease outcomes. Exhausted T cells manifest diminished effector function and proliferative potential, as they overexpress multiple inhibitory receptors, such as programmed cell death (PD)-1 and cytotoxic T lymphocyte antigen (CTLA)-4. These check-point molecules are among a long list of effective targets in cancer treatments, and their blockade reinvigorates dysfunctional T cells, thus, restoring anti-tumor immune responses. These immunotherapies have raised overall survival for various cancers to significant levels. However, some cancer aetiologies and even some patients with sensitive cancer types do not respond to these therapies or develop resistance after initial responsiveness. There is an urgent need to identify novel cancer/viral treatments, decipher mechanisms of resistance to immune-therapeutics, and to develop novel combination therapies and tumor vaccine strategies.

Research papers, reviews, and commentaries in this Special Issue will highlight mechanisms of novel immunotherapies, combination therapies, mechanisms of T cell exhaustion, and the role and function of different immune cells in chronic viral infections and cancer. Studies focussing on cancer vaccines are also welcome.

Dr. Tahseen H. Nasti
Dr. Christiane Eberhardt
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • anti-tumor responses
  • immune therapies
  • T cell exhaustion
  • check-point inhibitors
  • chronic viral infections
  • cancer vaccines

Published Papers (6 papers)

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Research

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Article
Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT
Vaccines 2021, 9(11), 1226; https://doi.org/10.3390/vaccines9111226 - 22 Oct 2021
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Abstract
BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status [...] Read more.
BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st–2nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with “non-reactive” anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-γ T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease. Full article
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Article
Biopharmaceutics 4.0, Advanced Pre-Clinical Development of mRNA-Encoded Monoclonal Antibodies to Immunosuppressed Murine Models
Vaccines 2021, 9(8), 890; https://doi.org/10.3390/vaccines9080890 - 11 Aug 2021
Cited by 1 | Viewed by 766
Abstract
Administration of mRNA against SARS-CoV-2 has demonstrated sufficient efficacy, tolerability and clinical potential to disrupt the vaccination field. A multiple-arm, cohort randomized, mixed blind, placebo-controlled study was designed to investigate the in vivo expression of mRNA antibodies to immunosuppressed murine models to conduct [...] Read more.
Administration of mRNA against SARS-CoV-2 has demonstrated sufficient efficacy, tolerability and clinical potential to disrupt the vaccination field. A multiple-arm, cohort randomized, mixed blind, placebo-controlled study was designed to investigate the in vivo expression of mRNA antibodies to immunosuppressed murine models to conduct efficacy, safety and bioavailability evaluation. Enabling 4.0 tools we reduced animal sacrifice, while interventions were designed compliant to HARRP and SPIRIT engagement: (a) Randomization, blinding; (b) pharmaceutical grade formulation, monitoring; (c) biochemical and histological analysis; and (d) theoretic, statistical analysis. Risk assessment molded the study orientations, according to the ARRIVE guidelines. The primary target of this protocol is the validation of the research hypothesis that autologous translation of Trastuzumab by in vitro transcribed mRNA-encoded antibodies to immunosuppressed animal models, is non-inferior to classical treatments. The secondary target is the comparative pharmacokinetic assessment of the novel scheme, between immunodeficient and healthy subjects. Herein, the debut clinical protocol, investigating the pharmacokinetic/pharmacodynamic impact of mRNA vaccination to immunodeficient organisms. Our design, contributes novel methodology to guide the preclinical development of RNA antibody modalities by resolving efficacy, tolerability and dose regime adjustment for special populations that are incapable of humoral defense. Full article
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Review

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Review
Vaccination against Cancer or Infectious Agents during Checkpoint Inhibitor Therapy
Vaccines 2021, 9(12), 1396; https://doi.org/10.3390/vaccines9121396 - 25 Nov 2021
Viewed by 197
Abstract
The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic [...] Read more.
The use of immune checkpoint inhibitors (ICI) has substantially increased the overall survival of cancer patients and has revolutionized the therapeutic situation in oncology. However, not all patients and cancer types respond to ICI, or become resistant over time. Combining ICIs with therapeutic cancer vaccines is a promising option as vaccination may help to overcome resistance to immunotherapies while immunotherapies may increase immune responses to the particular cancer vaccine by reinvigorating exhausted T cells. Thus, it would be possible to reprogram a response with appropriate vaccines, using a particular cancer antigen and a corresponding ICI. Target populations include currently untreatable cancer patients or those who receive treatment regimens with high risk of serious side effects. In addition, with the increased use of ICI in clinical practice, questions arise regarding safety and efficacy of administration of conventional vaccines, such as influenza or COVID-19 vaccines, during active ICI treatment. This review discusses the main principles of prophylactic and therapeutic cancer vaccines, the potential impact on combining therapeutic cancer vaccines with ICI, and briefly summarizes the current knowledge of safety and effectiveness of influenza and COVID-19 vaccines in ICI-treated patients. Full article
Review
Nucleotide Pool Imbalance and Antibody Gene Diversification
Vaccines 2021, 9(10), 1050; https://doi.org/10.3390/vaccines9101050 - 22 Sep 2021
Viewed by 669
Abstract
The availability and adequate balance of deoxyribonucleoside triphosphate (dNTP) is an important determinant of both the fidelity and the processivity of DNA polymerases. Therefore, maintaining an optimal balance of the dNTP pool is critical for genomic stability in replicating and quiescent cells. Since [...] Read more.
The availability and adequate balance of deoxyribonucleoside triphosphate (dNTP) is an important determinant of both the fidelity and the processivity of DNA polymerases. Therefore, maintaining an optimal balance of the dNTP pool is critical for genomic stability in replicating and quiescent cells. Since DNA synthesis is required not only in genomic replication but also in DNA damage repair and recombination, the abnormalities in the dNTP pool affect a wide range of chromosomal activities. The generation of antibody diversity relies on antigen-independent V(D)J recombination, as well as antigen-dependent somatic hypermutation and class switch recombination. These processes involve diverse sets of DNA polymerases, which are affected by the dNTP pool imbalances. This review discusses the role of the optimal dNTP pool balance in the diversification of antibody encoding genes. Full article
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Review
Role of NKT Cells during Viral Infection and the Development of NKT Cell-Based Nanovaccines
Vaccines 2021, 9(9), 949; https://doi.org/10.3390/vaccines9090949 - 26 Aug 2021
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Abstract
Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and [...] Read more.
Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and the strategies of viruses to evade the functioning of NKT cell have been illustrated. The nanoparticle-based formulations have superior immunoadjuvant potential by facilitating the efficient antigen processing and presentation that favorably elicits the antigen-specific immune response. Finally, the immunoadjuvant potential of the NKT cell ligand was explored in the development of antiviral vaccines. The use of an NKT cell-activating nanoparticle-based vaccine delivery system was supported in order to avoid the NKT cell anergy. The results from the animal and preclinical studies demonstrated that nanoparticle-incorporated NKT cell ligands may have potential implications as an immunoadjuvant in the formulation of an effective antiviral vaccine that is capable of eliciting the antigen-specific activation of the cell-mediated and humoral immune responses. Full article
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Review
Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer
Vaccines 2021, 9(5), 454; https://doi.org/10.3390/vaccines9050454 - 04 May 2021
Cited by 1 | Viewed by 766
Abstract
Immunotherapy has become a standard treatment in many cancers and it is based on three main therapeutic axes: immune checkpoint blockade (ICB), vaccination and adoptive cell transfer (ACT). If originally these therapies mainly focused on exploiting CD8 T cells given their role in [...] Read more.
Immunotherapy has become a standard treatment in many cancers and it is based on three main therapeutic axes: immune checkpoint blockade (ICB), vaccination and adoptive cell transfer (ACT). If originally these therapies mainly focused on exploiting CD8 T cells given their role in the direct elimination of tumor cells, increasing evidence highlights the crucial role CD4 T cells play in the antitumor immune response. Indeed, these cells can profoundly modulate the tumor microenvironment (TME) by secreting different types of cytokine or by directly eliminating cancer cells. In this review, we describe how different CD4 T cell subsets can contribute to tumor immune responses during immunotherapy and the novel high-throughput immune monitoring tools that are expected to facilitate the study of CD4 T cells, at antigen-specific and single cell level, thus accelerating bench-to-bed translational research in cancer. Full article
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