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Vaccines
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Understanding Immune Responses to COVID-19 Vaccines
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Understanding Immune Responses to COVID-19 Vaccines

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 12568

Special Issue Editor

Dr. Federico De Marco

E-Mail Website
Guest Editor
Department of RDAT, the Regina Elena National Cancer Institute IRCCS, Via Elio Chianesi 53, 00144 Rome, Italy
Interests: viral (HPV) carcinogenesis; oxidative stress; ultraviolet radiation; skin carcinogenesis; cancer progression; cancer microenvironment; proteins' oxidation and carcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The availability of safe and effective vaccines for the SARS-CoV-2 virus proved crucial in containing and mitigating the COVID-19 pandemic globally. Despite the significant work conducted by the scientific and social communities and the great results achieved in containing the disease, there is a long way to go. Several critical biological and clinical issues must be addressed, including the emergence of variants and the short duration of protective immunity. These issues are not the only critical areas of inquiry, and questions relating to patients with disabilities, patients in critical age groups, and other frail individuals are yet to be adequately addressed.

To discuss and share the latest research results and develop new ideas, we are launching a Special Issue, entitled ‘Understanding Immune Responses to COVID-19 Vaccines’ which is actually the 2nd edition of ‘Immune Responses to COVID-19 Vaccines’.

Dr. Federico De Marco
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.

Keywords

  • variants and the short duration of protective immunity
  • immune responses
  • COVID-19 vaccines

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Related Special Issue

Published Papers (7 papers)

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Research

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15 pages, 1673 KiB  
Article
Tracking Immunity: An Increased Number of COVID-19 Boosters Increases the Longevity of Anti-RBD and Anti-RBD-Neutralizing Antibodies
by Ching-Wen Hou, Stacy Williams, Veronica Boyle, Alexa Roeder, Bradley Bobbett, Izamar Garcia, Giavanna Caruth, Mitch Magee, Yunro Chung, Douglas F. Lake, Joshua LaBaer and Vel Murugan
Vaccines 2025, 13(1), 61; https://doi.org/10.3390/vaccines13010061 - 12 Jan 2025
Viewed by 982
Abstract
Background/Objectives: Since the World Health Organization declared COVID-19 a pandemic in March 2020, the virus has caused multiple waves of infection globally. Arizona State University (ASU), the largest four-year university in the United States, offers a uniquely diverse setting for assessing immunity within [...] Read more.
Background/Objectives: Since the World Health Organization declared COVID-19 a pandemic in March 2020, the virus has caused multiple waves of infection globally. Arizona State University (ASU), the largest four-year university in the United States, offers a uniquely diverse setting for assessing immunity within a large community. This study aimed to test our hypothesis that an increased number of exposures to SARS-CoV-2 RBD through vaccination/boosters/infection will increase SARS-CoV-2 antibody seroprevalence by increasing the longevity of anti-RBD and anti-RBD-neutralizing antibodies. Methods: A serosurvey was conducted at ASU from 30 January to 3 February 2023. Participants completed questionnaires about demographics, respiratory infection history, symptoms, and COVID-19 vaccination status. Blood samples were analyzed for anti-receptor binding domain (RBD) IgG and anti-nucleocapsid (NC) antibodies, offering a comprehensive view of immunity from both natural infection and vaccination. Results: The seroprevalence of anti-RBD IgG antibodies was 96.2% (95% CI: 94.8–97.2%), and 64.9% (95% CI: 61.9–67.8%) of participants had anti-NC antibodies. Anti-RBD IgG levels correlated strongly with neutralizing antibody levels, and participants who received more vaccine doses showed higher levels of both anti-RBD IgG and neutralizing antibodies. Increasing the number of exposures through vaccination and/or infection resulted in higher and long-lasting antibodies. Conclusions: The high levels of anti-RBD antibodies observed reflect substantial vaccine uptake within this population. Ongoing vaccination efforts, especially as new variants emerge, are essential to maintaining protective antibody levels. These findings underscore the importance of sustained public health initiatives to support broad-based immunity and protection. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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21 pages, 6548 KiB  
Article
Network Analysis of Dysregulated Immune Response to COVID-19 mRNA Vaccination in Hemodialysis Patients
by Yi-Shin Chang, Jessica M. Lee, Kai Huang, Christen L. Vagts, Christian Ascoli, Russell Edafetanure-Ibeh, Yue Huang, Ruth A. Cherian, Nandini Sarup, Samantha R. Warpecha, Sunghyun Hwang, Rhea Goel, Benjamin A. Turturice, Cody Schott, Montserrat H. Martinez, Patricia W. Finn and David L. Perkins
Vaccines 2024, 12(10), 1146; https://doi.org/10.3390/vaccines12101146 - 7 Oct 2024
Viewed by 1813
Abstract
Introduction: End-stage renal disease (ESRD) results in immune dysfunction that is characterized by both systemic inflammation and immune incompetence, leading to impaired responses to vaccination. Methods: To unravel the complex regulatory immune interplay in ESRD, we performed the network-based transcriptomic profiling of ESRD [...] Read more.
Introduction: End-stage renal disease (ESRD) results in immune dysfunction that is characterized by both systemic inflammation and immune incompetence, leading to impaired responses to vaccination. Methods: To unravel the complex regulatory immune interplay in ESRD, we performed the network-based transcriptomic profiling of ESRD patients on maintenance hemodialysis (HD) and matched healthy controls (HCs) who received the two-dose regimen of the COVID-19 mRNA vaccine BNT162b2. Results: Co-expression networks based on blood transcription modules (BTMs) of genes differentially expressed between the HD and HC groups revealed co-expression patterns that were highly similar between the two groups but weaker in magnitude in the HD compared to HC subjects. These networks also showed weakened coregulation between BTMs within the dendritic cell (DC) family as well as with other BTM families involved with innate immunity. The gene regulatory networks of the most enriched BTMs, likewise, highlighted weakened targeting by transcription factors of key genes implicated in DC, natural killer (NK) cell, and T cell activation and function. The computational deconvolution of immune cell populations further bolstered these findings with discrepant proportions of conventional DC subtypes, NK T cells, and CD8+ T cells in HD subjects relative to HCs. Conclusion: Altogether, our results indicate that constitutive inflammation in ESRD compromises the activation of DCs and NK cells, and, ultimately, their mediation of downstream lymphocytes, leading to a delayed but intact immune response to mRNA vaccination. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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15 pages, 1688 KiB  
Article
SARS-CoV-2-Specific T Lymphocytes Analysis in mRNA-Vaccinated Patients with B-Cell Lymphoid Malignancies on Active Treatment
by Patricia García Ramírez, Marta Callejas Charavia, Raquel Oliva Martin, Ana María Gómez La Hoz, Miguel Ángel Ortega, Julio García Suárez, Melchor Álvarez-Mon and Jorge Monserrat Sanz
Vaccines 2024, 12(9), 961; https://doi.org/10.3390/vaccines12090961 - 26 Aug 2024
Viewed by 1247
Abstract
Background: Patients with B-lymphocyte malignancies (BCMs) receiving B-lymphocyte-targeted therapies have increased risk of severe COVID-19 outcomes and impaired antibody response to SARS-CoV-2 mRNA vaccination in comparison to non-hematologic oncologic patients or general population. Consequently, it is vital to explore vaccine-induced T-lymphocyte responses in [...] Read more.
Background: Patients with B-lymphocyte malignancies (BCMs) receiving B-lymphocyte-targeted therapies have increased risk of severe COVID-19 outcomes and impaired antibody response to SARS-CoV-2 mRNA vaccination in comparison to non-hematologic oncologic patients or general population. Consequently, it is vital to explore vaccine-induced T-lymphocyte responses in patients referred for the understanding of immune protection against SARS-CoV2 infections. The objective of the present study was to analyze the recall immune responses carried out by T lymphocytes after two COVID-19 mRNA vaccine doses. Methods: We enrolled 40 patients with BCMs and 10 healthy controls (HCs) after 4 weeks from the second mRNA vaccine dose. Spike (S)-specific T-lymphocyte responses were assessed in peripheral blood mononuclear lymphocytes (PBMCs) by intracellular IFN-γ staining combined with flow cytometry. Furthermore, the humoral response was assessed with the measurement of anti-spike antibodies. Results: From March to July 2021, 40 patients (median age 68) received mRNA vaccines. The overall antibody response for BCMs was 52.5% versus 100% for the healthy controls (p = 0.008). The antibody response was different across BCMs: 18.75% for non-Hodgkin lymphoma, 54.5% for chronic lymphocytic leukemia, and 92.3% for multiple myeloma. Responses varied by malignancy type and treatment, with anti-CD20 therapies showing the lowest response (6.7%). T-lymphocyte analysis revealed reduced numbers and altered differentiation stages in patients compared to the controls. However, the vaccine-induced T response was generally robust, with variations in specific T subpopulations. Conclusions: mRNA vaccines induced significant humoral and cellular immune responses in B-cell lymphoid malignancy patients, although responses varied by treatment type and malignancy. Further research is needed to optimize vaccination strategies in this population. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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14 pages, 1862 KiB  
Article
Time-Dependent Effects of Clinical Interventions on SARS-CoV-2 Immunity in Patients with Lung Cancer
by Philip C. Mack, Chih-Yuan Hsu, Ananda M. Rodilla, Jorge E. Gomez, Jazz Cagan, Yuanhui Huang, Sooyun Tavolacci, Rajesh M. Valanparambil, Nicholas Rohs, Rachel Brody, Brittney Nichols, Juan Manuel Carreño, Sheena Bhalla, Christian Rolfo, David E. Gerber, Amy Moore, Jennifer C. King, Rafi Ahmed, John D. Minna, Paul A. Bunn, Jr., Adolfo García-Sastre, Florian Krammer, Fred R. Hirsch and Yu Shyradd Show full author list remove Hide full author list
Vaccines 2024, 12(7), 713; https://doi.org/10.3390/vaccines12070713 - 26 Jun 2024
Cited by 1 | Viewed by 2501
Abstract
In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to [...] Read more.
In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients—median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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13 pages, 1287 KiB  
Article
Comparative Analysis of SARS-CoV-2 Antibody Responses across Global and Lesser-Studied Vaccines
by José Victor Zambrana, Carlos Saenz, Hannah E. Maier, Mayling Brenes, Andrea Nuñez, Anita Matamoros, Mabel Hernández, Keyla Dumas, Cristhian Toledo, Leonardo Peralta, Aubree Gordon and Angel Balmaseda
Vaccines 2024, 12(3), 326; https://doi.org/10.3390/vaccines12030326 - 19 Mar 2024
Cited by 2 | Viewed by 2081
Abstract
Few data are available on antibody response for some SARS-CoV-2 vaccines, and there is a lack of ability to compare vaccine responses in the same population. This cross-sectional study conducted in Nicaragua examines the SARS-CoV-2 antibody responses in individuals, previously exposed to high [...] Read more.
Few data are available on antibody response for some SARS-CoV-2 vaccines, and there is a lack of ability to compare vaccine responses in the same population. This cross-sectional study conducted in Nicaragua examines the SARS-CoV-2 antibody responses in individuals, previously exposed to high infection rates who have received various vaccines. The vaccines under comparison include well-known ones like Pfizer (BNT162b2) and AstraZeneca (ChAdOx1-S), alongside less-studied vaccines including Soberana (Soberana 02), Abdala (CIGB-66), and Sputnik V/Sputnik Light. Overall, 3195 individuals participated, with 2862 vaccinated and 333 unvaccinated. We found that 95% of the unvaccinated were seropositive, with much lower titers than the vaccinated. Among the vaccinated, we found that Soberana recipients mounted the highest anti-spike response (mean difference (MD) = 36,498.8 [20,312.2, 52,685.5]), followed by Abdala (MD = 25,889.9 [10,884.1, 40,895.7]), BNT162b2 (MD = 12,967.2 [7543.7, 18,390.8]) and Sputnik with AstraZeneca as the reference group, adjusting for age, sex, vaccine status, days after last dose, and self-reported COVID-19. In addition, we found that subjects with complete vaccination series had higher antibody magnitude than those with incomplete series. Overall, we found no evidence of waning in the antibody magnitude across vaccines. Our study supports the conclusion that populations with high infection rates still benefit substantially from vaccination. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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Review

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25 pages, 1717 KiB  
Review
The Impact of HIV on B Cell Compartment and Its Implications for COVID-19 Vaccinations in People with HIV
by Lixing Wang, Branka Vulesevic, MariaLuisa Vigano, Alia As’sadiq, Kristina Kang, Cristina Fernandez, Suzanne Samarani, Aslam H. Anis, Ali Ahmad and Cecilia T. Costiniuk
Vaccines 2024, 12(12), 1372; https://doi.org/10.3390/vaccines12121372 - 5 Dec 2024
Viewed by 1104
Abstract
HIV causes intense polyclonal activation of B cells, resulting in increased numbers of spontaneously antibody-secreting cells in the circulation and hypergammaglobulinemia. It is accompanied by significant perturbations in various B cell subsets, such as increased frequencies of immature/transitional B cells, activated memory B [...] Read more.
HIV causes intense polyclonal activation of B cells, resulting in increased numbers of spontaneously antibody-secreting cells in the circulation and hypergammaglobulinemia. It is accompanied by significant perturbations in various B cell subsets, such as increased frequencies of immature/transitional B cells, activated memory B cells, atypical memory B cells, short-lived plasmablasts and regulatory B cells, as well as by decreased frequencies of resting memory and resting naïve B cells. Furthermore, both memory and antigen-inexperienced naïve B cells show exhausted and immune-senescent phenotypes. HIV also drives the expansion and functional impairment of CD4+ T follicular helper cells, which provide help to B cells, crucial for the generation of germinal center reactions and production of long-lived plasma and memory B cells. By suppressing viral replication, anti-retroviral therapy reverses the virus-induced perturbations and functional defects, albeit inadequately. Due to HIV’s lingering impact on B cells, immune senescence and residual chronic inflammation, people with HIV (PWH), especially immune non-responders, are immunocompromised and mount suboptimal antibody responses to vaccination for SARS-CoV-2. Here, we review how functionally and phenotypically distinct B cell subsets are induced in response to a vaccine and an infection and how HIV infection and anti-retroviral therapy (ART) impact them. We also review the role played by HIV-induced defects and perturbations in B cells in the induction of humoral immune responses to currently used anti-SARS-CoV-2 vaccines in PWH on ART. We also outline different strategies that could potentially enhance the vaccine-induced antibody responses in PWH. The review will provide guidance and impetus for further research to improve the immunogenicity of these vaccines in this human population. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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24 pages, 2342 KiB  
Review
T-Cell Immune Responses to SARS-CoV-2 Infection and Vaccination
by Samuele Notarbartolo
Vaccines 2024, 12(10), 1126; https://doi.org/10.3390/vaccines12101126 - 30 Sep 2024
Viewed by 1910
Abstract
The innate and adaptive immune systems collaborate to detect SARS-CoV-2 infection, minimize the viral spread, and kill infected cells, ultimately leading to the resolution of the infection. The adaptive immune system develops a memory of previous encounters with the virus, providing enhanced responses [...] Read more.
The innate and adaptive immune systems collaborate to detect SARS-CoV-2 infection, minimize the viral spread, and kill infected cells, ultimately leading to the resolution of the infection. The adaptive immune system develops a memory of previous encounters with the virus, providing enhanced responses when rechallenged by the same pathogen. Such immunological memory is the basis of vaccine function. Here, we review the current knowledge on the immune response to SARS-CoV-2 infection and vaccination, focusing on the pivotal role of T cells in establishing protective immunity against the virus. After providing an overview of the immune response to SARS-CoV-2 infection, we describe the main features of SARS-CoV-2-specific CD4+ and CD8+ T cells, including cross-reactive T cells, generated in patients with different degrees of COVID-19 severity, and of Spike-specific CD4+ and CD8+ T cells induced by vaccines. Finally, we discuss T-cell responses to SARS-CoV-2 variants and hybrid immunity and conclude by highlighting possible strategies to improve the efficacy of COVID-19 vaccination. Full article
(This article belongs to the Special Issue Understanding Immune Responses to COVID-19 Vaccines)
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