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Vaccines
Special Issues
The Development of Peptide-Based Vaccines
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The Development of Peptide-Based Vaccines

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

Deadline for manuscript submissions: 30 September 2026 | Viewed by 3430

Special Issue Editors

Dr. José Manuel Pérez De La Lastra

E-Mail Website
Guest Editor
Biotechnology of Macromolcules, Instituto de Productos Naturales y Agrobiología, CSIC, 28006 Madrid, Spain
Interests: biotechnology; macromolecules; antimicrobials; IgY antibodies; peptides; epitopes
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. José de la Fuente

E-Mail Website
Guest Editor
1. SaBio, IREC (CSIC-UCLM-JCCM), Ciudad Real, Spain
2. Department of Veterinary Pathobiology, CVHS, Oklahoma State University, Stillwater, OK, USA
Interests: infectious diseases; molecular biology of host-vector-pathogen interactions; gene regulation; pathogenesis; functional genomics; evolution and immunology; systems biology; ticks and tick-borne diseases; intracellular bacteria (Rickettsia, Anaplasma, Mycobacterium); vaccinology; biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue covers a wide range of topics, including the design and synthesis of peptide antigens, strategies to enhance immunogenicity, and innovative delivery systems. We invite contributions that go beyond predicted outcomes, specifically focusing on experimental evidence demonstrating that immunogens are immunogenic and elicit an appropriate immune response. Papers addressing the molecular mechanisms underlying the efficacy of peptide vaccines, the role of adjuvants, and the challenges of translating preclinical findings into clinical applications are particularly welcome.

This Special Issue will also highlight the emerging use of peptide vaccines in combating infectious diseases, cancer, and autoimmune diseases. Special attention will be given to novel approaches such as multi-epitope and personalized peptide vaccines, as well as the integration of computational tools in peptide vaccine development. This Special Issue aims to bring together researchers from diverse fields to foster interdisciplinary collaboration and provide a platform for the exchange of cutting-edge research that demonstrates real-world efficacy, paving the way for the next generation of peptide vaccines.

Dr. José Manuel Pérez De La Lastra
Prof. Dr. José de la Fuente
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 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 250 words) can be sent to the Editorial Office for assessment.

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.

Keywords

  • peptide antigens
  • vaccine design
  • immunogenicity
  • epitope mapping
  • adjuvants
  • multi-epitope vaccines
  • personalized peptide vaccines
  • vaccine delivery systems
  • computational vaccine design
  • synthetic peptides

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Published Papers (3 papers)

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Review

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13 pages, 533 KB  
Review
Peptide Vaccines for Pediatric High-Grade Glioma and Diffuse Midline Glioma: Current Progress and Future Perspectives
by Aron K. Mebrahtu, Vatsal Jain, Eliese M. Moelker, Alexandra M. Hoyt-Miggelbrink, Katayoun Ayasoufi and Eric M. Thompson
Vaccines 2025, 13(12), 1215; https://doi.org/10.3390/vaccines13121215 - 30 Nov 2025
Viewed by 540
Abstract
High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we [...] Read more.
High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed at inducing potent, tumor-specific T-cell responses. In this review, we define the scope of current progress by arguing that immunogenicity in children with HGG/DMG hinges on three factors: appropriate antigen class (neoantigen vs. TAA), the use of potent immunoadjuvants, and successful navigation of immune suppression. To address the gap between biological promise and clinical reality, we analyze clinical trials targeting shared tumor-associated antigens (e.g., CMV pp65, Survivin) and specific shared neoantigens (H3.3K27M). Crucially, we highlight pivotal data from the PNOC007 trial, where the magnitude of H3.3K27M-specific T-cell expansion correlated directly with significantly longer overall survival (OS), establishing a causal link between pharmacodynamics and clinical benefit. However, the unique challenges of the immunosuppressive tumor microenvironment and the detrimental effect of necessary corticosteroids remain paramount barriers. Future success relies on multi-modal combination strategies, the development of next-generation personalized neoantigen vaccines, and the application of advanced neuroimaging to accurately assess treatment response. Full article
(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)
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18 pages, 1162 KB  
Review
Shaping Antitumor Immunity with Peptide Vaccines: Implications of Immune Modulation at the Vaccine Site
by Amrita Sarkar, Emily Pauline Rabinovich and Craig Lee Slingluff, Jr.
Vaccines 2025, 13(11), 1150; https://doi.org/10.3390/vaccines13111150 - 11 Nov 2025
Viewed by 729
Abstract
Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, [...] Read more.
Cancer vaccines have emerged as a class of therapeutics designed to harness the immune system to stimulate durable anti-tumor responses with lower systemic toxicity than conventional therapies. Many platforms have been explored, including protein, peptide, DNA, RNA, and cell-based vaccines. Within this landscape, peptide vaccines remain a promising approach. Most clinical trials have examined peripheral immune responses and clinical outcomes, but there is growing interest in the vaccine site microenvironment (VSME) as a window to understand local immune activation and its implications for systemic immunity and tumor control. Studies of the VSME have investigated the effects of adjuvants, local immune cell dynamics, and their correlation with systemic responses and outcomes. Local adjuvants typically enhance immune cell infiltration, though there are concerns regarding VSME sequestration or dysfunction of immune cells, which could impact systemic efficacy. Repeated vaccination at a single site may improve antigen presentation and immune responses, but factors such as injection site location may be linked to variability in clinical outcomes. Current studies are limited by substantial variability in sampling, timing, and analyses used in VSME assessment. This limits the comparability of findings and broader inferences regarding the influence of vaccine site dynamics on therapeutic efficacy. Standardized VSME assessment as part of future vaccine trials may improve evaluation of immune responses and provide a more consistent surrogate for vaccine effectiveness. This refinement may inform optimal vaccine strategies and further support the development of next-generation cancer immunotherapies. Full article
(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)
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Other

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10 pages, 1220 KB  
Case Report
Case Report: A Multi-Peptide Vaccine Targeting Individual Somatic Mutations Induces Tumor Infiltration of Neoantigen-Specific T Cells in a Patient with Metastatic Colorectal Cancer
by Armin Rabsteyn, Henning Zelba, Borong Shao, Lisa Oenning, Christina Kyzirakos, Simone Kayser, Tabea Riedlinger, Johannes Harter, Magdalena Feldhahn, Dirk Hadaschik, Florian Battke, Veit Scheble, Alfred Königsrainer and Saskia Biskup
Vaccines 2025, 13(9), 960; https://doi.org/10.3390/vaccines13090960 - 11 Sep 2025
Viewed by 1508
Abstract
Background/Objectives: Fully personalized peptide vaccines targeting tumor-specific mutations are a promising treatment option for patients in an adjuvant but also advanced/metastatic disease situation in addition to non-personalized standard therapies. Here, we report a patient’s case with advanced metastatic colorectal cancer (mCRC) who was [...] Read more.
Background/Objectives: Fully personalized peptide vaccines targeting tumor-specific mutations are a promising treatment option for patients in an adjuvant but also advanced/metastatic disease situation in addition to non-personalized standard therapies. Here, we report a patient’s case with advanced metastatic colorectal cancer (mCRC) who was treated with a neoantigen-derived multi-peptide vaccine in addition to standard of care. Methods: Tumor-specific mutations were identified by whole exome and transcriptome sequencing. An individualized peptide vaccine was designed using an in-house developed epitope prediction and vaccine design platform. In this case, the vaccine consisted of 20 peptides targeting 18 distinct mutations. The vaccine was administered according to a prime-boost scheme for a total of 12 vaccinations. Vaccine immunogenicity was determined by stimulation of patient T cells with vaccinated peptides and subsequent intracellular cytokine staining (ICS). Tumor-infiltrating lymphocytes (TIL) were analyzed by ICS and T cell receptor beta chain (TCRβ) sequencing. Results: The patient survived for 41 months since initial diagnosis despite continuous disease progression under all therapeutic interventions. The vaccination induced multiple neoantigen-specific T cell responses in the patient without notable side effects. Two liver metastases were resected five months after the start of vaccination, and TIL were extracted and cultured. Analysis of TIL cultures revealed tumor infiltration by vaccine-induced neoantigen-specific T cells in only one of the metastases. TCRβ sequencing of neoantigen-specific T cells and tumor tissues supported this finding. Vaccine-targeted variants were reduced or absent in the metastasis with vaccine-specific T cell infiltration. Conclusions: This case demonstrates immunogenicity of a neoantigen-derived peptide vaccine and highlights tumor-infiltrating capabilities and potential cytotoxicity of vaccine-induced T cells in mCRC. Full article
(This article belongs to the Special Issue The Development of Peptide-Based Vaccines)
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