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Vaccines
Special Issues
Analysis of Vaccine-Induced Adaptive Immune Responses
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Analysis of Vaccine-Induced Adaptive Immune Responses

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Innate and Adaptive Immunity in Vaccination".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 5144

Special Issue Editors

Dr. Francesco Nicoli

E-Mail Website
Guest Editor
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44123 Ferrara, Italy
Interests: vaccine development; viral infections; immune responses; immunosenescence; immunometabolism
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Antonella Caputo

E-Mail Website
Guest Editor
Department of Chemical, Pharmacological and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy
Interests: vaccine development; viral infections; immune responses
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

B and T cells play key roles in adaptive immune responses. Research into cellular immunology provides an understanding of T cell recognition, activation and dysregulation, and their roles in protecting against infectious diseases and cancer and autoimmune diseases. Similarly, studies in the field of humoral immunity are crucial to determine the roles of antibodies in providing such protection, the functionality of different immunoglobulins, and the activity of distinct B cell subsets.

In recent years, new sophisticated and cutting-edge methodologies have become available, allowing us to gain insights into lymphocyte biology and functions and their mechanisms of action. These innovative techniques can represent extremely useful tools to characterize vaccine-induced cellular and humoral responses.

This Special Issue will focus on the advances and application of these new methodologies in studying cellular and humoral immunity against vaccine-preventable infectious diseases. We request original comprehensive research articles and reviews on this topic, which must be focused on the keywords reported below and explain how these studies have changed or enhanced our understanding of T cell immunity.

Dr. Francesco Nicoli
Prof. Dr. Antonella Caputo
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 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.

Keywords

  • RNA sequencing
  • flow cytometry
  • microscopy
  • T cells
  • B cells
  • antibodies
  • biochemistry
  • molecular biology
  • systems biology
  • epitope prediction

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Published Papers (4 papers)

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Research

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20 pages, 2762 KiB  
Article
Vaccination Against RhoC in Prostate Cancer Patients Induces Potent and Long-Lasting CD4+ T Cell Responses with Cytolytic Potential in the Absence of Clinical Efficacy: A Randomized Phase II Trial
by Sara Fresnillo Saló, Juliane Schuhmacher, Anne Rahbech, Sara Ram Pedersen, Tina Seremet, Valero Andreu Matillas, Anna Schöllhorn, Andreas Røder, Steffen Wad Jørgensen, Klaus Brasso, Cécile Gouttefangeas, Per thor Straten and on behalf of the RhoVac-002 Study Group
Vaccines 2025, 13(4), 390; https://doi.org/10.3390/vaccines13040390 - 5 Apr 2025
Viewed by 622
Abstract
Background: A previous phase I/II study demonstrated potent and long-term immune responses in men with prostate cancer following vaccination with a 20mer synthetic peptide (RV001) derived from the Ras homolog gene family member C protein (RhoC). Moreover, a fraction of patients experienced [...] Read more.
Background: A previous phase I/II study demonstrated potent and long-term immune responses in men with prostate cancer following vaccination with a 20mer synthetic peptide (RV001) derived from the Ras homolog gene family member C protein (RhoC). Moreover, a fraction of patients experienced prostate-specific antigen (PSA) responses, which prompted the initiation of a phase II double-blind randomized trial (NCT04114825). The primary endpoint was to study whether vaccination could postpone PSA progression. Furthermore, the study included an evaluation of vaccination-induced immune responses, and in-depth in vitro studies of RhoC-specific CD4+ T cell responses. Methods: Men with non-metastatic biochemical recurrence after either radical prostatectomy or radiation therapy were eligible for the study. Participants were randomized 1:1 to either subcutaneous injections of 0.1 mg/mL RV001 emulsified in Montanide ISA 51, or a placebo. Vaccinations were administered every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. Blood samples were collected from a subset of patients (n = 38) over the course of vaccination, and peripheral blood mononuclear cells (PBMCs) isolated for immunological assessment of vaccine-induced immune responses. Experiments using PBMCs from a healthy donor and a patient were performed to study the phenotype and function of RV001-specific CD4+ T cells. Results: A total of 192 men entered the study. There was no difference in time to PSA doubling, with 7.5 versus 9.3 months, or in time to initiating further therapies, 11.2 versus 17.6 months for treatment and control groups, respectively. At long-term follow-up, 12.9% of the patients in the vaccination arm had developed metastasis compared to 12% in the placebo arm. No serious treatment-related side effects were observed, and treatment-related adverse events did not differ between groups. Immunological examinations in a subset of patients demonstrated that the vaccination induced potent, long-lasting CD4+ T cell responses capable of proliferation and cytokine production. RV001-specific CD4+ T cells were shown to mediate cytotoxicity against a RhoC-expressing cancer cell line in an HLA-class II-dependent manner. Conclusions: Men randomized to active treatment with RV001V demonstrated the induction of potent, functionally capable, anti RhoC-CD4+ T cell responses. However, there was no benefit in time to biochemical progression, and no difference in time to the initiation of second-line therapies. Full article
(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)
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10 pages, 1177 KiB  
Article
Sequential SARS-CoV-2 mRNA Vaccination Induces Anti-Idiotype (Anti-ACE2) Antibodies in K18 Human ACE2 Transgenic Mice
by Craig P. Collins, Christian Herzog, Logan V. Vick, Ryan Nielsen, Yanping Izak Harville, Dan L. Longo, John M. Arthur and William J. Murphy
Vaccines 2025, 13(3), 224; https://doi.org/10.3390/vaccines13030224 - 24 Feb 2025
Viewed by 847
Abstract
Background/Objectives: Novel mRNA vaccines have been successfully utilized to curtail the SARS-CoV-2 pandemic. However, the immunology underlying CoV2 vaccinations, particularly with repeated boosting, has not been properly characterized due to limitations in the preclinical modeling of SARS-CoV-2 infection/vaccinations as well as constantly changing [...] Read more.
Background/Objectives: Novel mRNA vaccines have been successfully utilized to curtail the SARS-CoV-2 pandemic. However, the immunology underlying CoV2 vaccinations, particularly with repeated boosting, has not been properly characterized due to limitations in the preclinical modeling of SARS-CoV-2 infection/vaccinations as well as constantly changing vaccine formulations. The immunoregulatory aspects involved in such vaccine approaches remain unclear. Antibodies, due to inherent immunogenicity by VDJ gene rearrangement, have the potential to induce antibodies directed towards them called anti-idiotype antibodies, which can play a downregulatory role in responses. The paratope of some of these anti-idiotype antibodies can also act as a mirror to the original antigen, which, in the case of SARS-CoV-2 vaccines, would be to the spike protein and, therefore, also be capable of binding its target, ACE2, potentially causing adverse effects. Methods: To investigate if sequential SARS-CoV-2 mRNA vaccination can induce anti-idiotype antibody responses, K18 hACE2 transgenic mice were serially vaccinated with a SARS-CoV-2 mRNA construct to determine the kinetics of anti-spike and anti-ACE2 responses via custom-made ELISAs. Results: While sequential vaccination produced robust anti-spike responses, anti-ACE2 levels were also detected and gradually amplified with each boost. These anti-ACE2 antibodies persisted for 3 months after the final vaccination and showed evidence of hACE2 binding, as levels were lower in K18 mice in comparison to the wild type. Conclusions: These data would suggest that sequential SARS-CoV-2 mRNA vaccination has the potential to induce anti-ACE2 antibodies in mice, with each boost amplifying the amount of antibody. Full article
(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)
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Review

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22 pages, 1487 KiB  
Review
Monitoring Immune Responses to Vaccination: A Focus on Single-Cell Analysis and Associated Challenges
by LaToya Montgomery and Anis Larbi
Vaccines 2025, 13(4), 420; https://doi.org/10.3390/vaccines13040420 - 16 Apr 2025
Viewed by 588
Abstract
Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability [...] Read more.
Monitoring the immune response to vaccination encompasses both significant challenges and promising opportunities for scientific advancement. The primary challenge lies in the inherent complexity and interindividual variability of immune responses, influenced by factors including age, genetic background, and prior immunological history. This variability necessitates the development of sophisticated, highly sensitive assays capable of accurately quantifying immune parameters such as antibody titers, T-cell responses, and cytokine profiles. Furthermore, the temporal dynamics of the immune response require comprehensive longitudinal studies to elucidate the durability and quality of vaccine-induced immunity. Challenges of this magnitude pave the way for immunological research advancements and diagnostic methodologies. Cutting-edge monitoring techniques, such as high-throughput sequencing and advanced flow cytometry, enable deeper insights into the mechanistic underpinnings of vaccine efficacy and contribute to the iterative design of more effective vaccines. Additionally, the integration of analytical tools holds the potential to predict immune responses and tailor personalized vaccination strategies. This will be addressed in this review to provide insight for enhancing public health outcomes and fortifying preparedness against future infectious disease threats. Full article
(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)
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16 pages, 615 KiB  
Review
Durability of Adaptive Immunity in Immunocompetent and Immunocompromised Patients Across Different Respiratory Viruses: RSV, Influenza, and SARS-CoV-2
by Achilleas Livieratos, Lars Erik Schiro, Charalambos Gogos and Karolina Akinosoglou
Vaccines 2024, 12(12), 1444; https://doi.org/10.3390/vaccines12121444 - 22 Dec 2024
Viewed by 2033
Abstract
Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives [...] Read more.
Background/Objectives. Research on respiratory virus immunity duration post-vaccination reveals variable outcomes. This study performed a literature review to assess the efficacy and longevity of immune protection post-vaccination against SARS-CoV-2, influenza, and respiratory syncytial virus (RSV), with a focus on immunocompromised populations. Specific objectives included examining humoral and cellular immune responses and exploring the impact of booster doses and hybrid immunity on extending protection. Methods. A literature review was conducted focusing on studies published from January 2014 to November 2024. The search targeted adaptive immunity post-vaccination, natural immunity, and hybrid immunity for SARS-CoV-2, influenza, and RSV. Selection criteria emphasized human populations, adaptive immunity outcomes, and immunocompromised individuals. The PICO framework guided the analysis, culminating in a detailed review of 30 studies. Results. SARS-CoV-2 vaccines exhibited robust initial antibody responses, which waned significantly within six months, necessitating frequent boosters. Influenza and RSV vaccines similarly showed declines in immunity, though some influenza vaccines demonstrated moderate durability. Hybrid immunity, arising from combined natural infection and vaccination, provided more resilient and lasting protection than vaccination alone, especially against emerging variants. Immunocompromised individuals consistently exhibited reduced durability in adaptive immune responses across all studied viruses. Challenges include rapid viral mutations, limiting the broad protection of current vaccines. Conclusions. Immune durability varies significantly across virus types and patient populations. Frequent boosters and hybrid immunity are critical to optimizing protection, particularly for vulnerable groups. The findings underscore the need for adaptable vaccination strategies and advancements in vaccine design to counter rapidly mutating respiratory pathogens effectively. Full article
(This article belongs to the Special Issue Analysis of Vaccine-Induced Adaptive Immune Responses)
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