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Vaccines
Special Issues
Taking Neo-Antigen Vaccines Forward
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Taking Neo-Antigen Vaccines Forward

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 13256

Special Issue Editor

Prof. Dr. Karim Vermaelen

E-Mail Website
Guest Editor
Department of Pulmonary Medicine, Ghent University, 9000 Ghent, Belgium
Interests: dendritic cells; lung cancer; cell therapy; neoantigens; immune checkpoint inhibitor or immune checkpoint blockade; vaccines

Special Issue Information

Dear Colleagues,

Inducing effective adaptive immune responses against neoantigens has become an intensively explored way to fight cancer. The idea is to enrich for highly tumor-specific T-cell responses, turning “cold” into “hot” tumors thus potentiating the effects of existing immunotherapies such as immune checkpoint blockade. This approach drives a revival of vaccines in oncology. Beyond the proof-of-concept in preclinical animal models, neoantigen vaccines are now being tested in numerous oncology clinical trials around the world.

However many challenges still exist before this approach can be adopted in routine clinical care. These issues pertain to the long and complex pipeline for patient-individual neoantigen discovery, which is long, complex, relies heavily on bioinformatic prediction algorithms,  and lacks standardization and often proper validation. Strategies to improve or accelerate these pipelines are needed. Regulatory issues pertaining to the highly personalized nature of these advanced therapies must also be considered.

This Special Issue aims to provide the reader with the State-of-the-Art in neoantigen vaccine development and give a glimpse of its future. Papers pertaining to genomic and proteomic neoantigen discovery pipelines, clinical applications and results so far, regulatory aspects of neoantigen-targeted therapies and other related topics are welcome. In addition to the field of cancer, papers dealing with the use of microbial-derived xeno-epitopes for vaccination purposes will be considered as well.

Prof. Dr. Karim Vermaelen
Guest Editor

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 submissions that pass pre-check are 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 2700 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.

Published Papers (3 papers)

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Research

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14 pages, 1520 KiB  
Article
VENUS, a Novel Selection Approach to Improve the Accuracy of Neoantigens’ Prediction
by Guido Leoni, Anna Morena D’Alise, Fabio Giovanni Tucci, Elisa Micarelli, Irene Garzia, Maria De Lucia, Francesca Langone, Linda Nocchi, Gabriella Cotugno, Rosa Bartolomeo, Giuseppina Romano, Simona Allocca, Fulvia Troise, Alfredo Nicosia, Armin Lahm and Elisa Scarselli
Vaccines 2021, 9(8), 880; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines9080880 - 09 Aug 2021
Cited by 7 | Viewed by 3424
Abstract
Neoantigens are tumor-specific antigens able to induce T-cell responses, generated by mutations in protein-coding regions of expressed genes. Previous studies demonstrated that only a limited subset of mutations generates neoantigens in microsatellite stable tumors. We developed a method, called VENUS (Vaccine-Encoded Neoantigens Unrestricted [...] Read more.
Neoantigens are tumor-specific antigens able to induce T-cell responses, generated by mutations in protein-coding regions of expressed genes. Previous studies demonstrated that only a limited subset of mutations generates neoantigens in microsatellite stable tumors. We developed a method, called VENUS (Vaccine-Encoded Neoantigens Unrestricted Selection), to prioritize mutated peptides with high potential to be neoantigens. Our method assigns to each mutation a weighted score that combines the mutation allelic frequency, the abundance of the transcript coding for the mutation, and the likelihood to bind the patient’s class-I major histocompatibility complex alleles. By ranking mutated peptides encoded by mutations detected in nine cancer patients, VENUS was able to select in the top 60 ranked peptides, the 95% of neoantigens experimentally validated including both CD8 and CD4 T cell specificities. VENUS was evaluated in a murine model in the context of vaccination with an adeno vector encoding the top ranked mutations prioritized in the MC38 cell line. Efficacy studies demonstrated anti tumoral activity of the vaccine when used in combination with checkpoint inhibitors. The results obtained highlight the importance of a combined scoring system taking into account multiple features of each tumor mutation to improve the accuracy of neoantigen prediction. Full article
(This article belongs to the Special Issue Taking Neo-Antigen Vaccines Forward)
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Review

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24 pages, 2196 KiB  
Review
Four Faces of Cell-Surface HLA Class-I: Their Antigenic and Immunogenic Divergence Generating Novel Targets for Vaccines
by Mepur H. Ravindranath, Narendranath M. Ravindranath, Senthamil R. Selvan, Edward J. Filippone, Carly J. Amato-Menker and Fatiha El Hilali
Vaccines 2022, 10(2), 339; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10020339 - 21 Feb 2022
Cited by 4 | Viewed by 2971
Abstract
Leukocyte cell-surface HLA-I molecules, involved in antigen presentation of peptides to CD8+ T-cells, consist of a heavy chain (HC) non-covalently linked to β2-microglobulin (β2m) (Face-1). The HC amino acid composition varies across all six isoforms of HLA-I, while that of β2m remains the [...] Read more.
Leukocyte cell-surface HLA-I molecules, involved in antigen presentation of peptides to CD8+ T-cells, consist of a heavy chain (HC) non-covalently linked to β2-microglobulin (β2m) (Face-1). The HC amino acid composition varies across all six isoforms of HLA-I, while that of β2m remains the same. Each HLA-allele differs in one or more amino acid sequences on the HC α1 and α2 helices, while several sequences among the three helices are conserved. HCs without β2m (Face-2) are also observed on human cells activated by malignancy, viral transformation, and cytokine or chemokine-mediated inflammation. In the absence of β2m, the monomeric Face-2 exposes immunogenic cryptic sequences on these cells as confirmed by HLA-I monoclonal antibodies (LA45, L31, TFL-006, and TFL-007). Furthermore, such exposure enables dimerization between two Face-2 molecules by SH-linkage, salt linkage, H-bonding, and van der Waal forces. In HLA-B27, the linkage between two heavy chains with cysteines at position of 67 of the amino acid residues was documented. Similarly, several alleles of HLA-A, B, C, E, F and G express cysteine at 67, 101, and 164, and additionally, HLA-G expresses cysteine at position 42. Thus, the monomeric HC (Face-2) can dimerize with another HC of its own allele, as homodimers (Face-3), or with a different HC-allele, as heterodimers (Face-4). The presence of Face-4 is well documented in HLA-F. The post-translational HLA-variants devoid of β2m may expose several cryptic linear and non-linear conformationally altered sequences to generate novel epitopes. The objective of this review, while unequivocally confirming the post-translational variants of HLA-I, is to highlight the scientific and clinical importance of the four faces of HLA and to prompt further research to elucidate their functions and their interaction with non-HLA molecules during inflammation, infection, malignancy and transplantation. Indeed, these HLA faces may constitute novel targets for passive and active specific immunotherapy and vaccines. Full article
(This article belongs to the Special Issue Taking Neo-Antigen Vaccines Forward)
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20 pages, 369 KiB  
Review
Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies
by Carson R. Reynolds, Son Tran, Mohit Jain and Aru Narendran
Vaccines 2022, 10(2), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines10020196 - 26 Jan 2022
Cited by 10 | Viewed by 5873
Abstract
Alternatives to conventional cancer treatments are highly sought after for high-risk malignancies that have a poor response to established treatment modalities. With research advancing rapidly in the past decade, neoantigen-based immunotherapeutic approaches represent an effective and highly tolerable therapeutic option. Neoantigens are tumor-specific [...] Read more.
Alternatives to conventional cancer treatments are highly sought after for high-risk malignancies that have a poor response to established treatment modalities. With research advancing rapidly in the past decade, neoantigen-based immunotherapeutic approaches represent an effective and highly tolerable therapeutic option. Neoantigens are tumor-specific antigens that are not expressed in normal cells and possess significant immunogenic potential. Several recent studies have described the conceptual framework and methodologies to generate neoantigen-based vaccines as well as the formulation of appropriate clinical trials to advance this approach for patient care. This review aims to describe some of the key studies in the recent literature in this rapidly evolving field and summarize the current advances in neoantigen identification and selection, vaccine generation and delivery, and the optimization of neoantigen-based therapeutic strategies, including the early data from pivotal clinical studies. Full article
(This article belongs to the Special Issue Taking Neo-Antigen Vaccines Forward)
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