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16 pages, 14586 KB  
Article
Vaccination with Two Doses of AstraZeneca® (ChAdOx1-S) and Pfizer® (BNT162b2) Induces the Production of Immunoglobulin G for COVID-19 Without Damaging Hematological, Biochemical, Inflammatory and Oxidative Biomarkers
by Laura Smolski dos Santos, Genifer Erminda Schreiner, Elizandra Gomes Schmitt, Mariana Larré da Silveira, Camila Berny Pereira, Luana Tamires Maders, Silvia Muller de Moura, Mohammad Prudêncio Mustafá, Itamar Luís Gonçalves, Ilson Dias da Silveira and Vanusa Manfredini
COVID 2026, 6(1), 15; https://doi.org/10.3390/covid6010015 - 6 Jan 2026
Viewed by 165
Abstract
Background: In 2019, a new virus caused by SARS-CoV-2, called COVID-19, spread throughout the world, causing a pandemic state. As the pandemic progressed and cases continued to increase, safe vaccines were developed for the entire population. In Brazil, AstraZeneca® (ChAdOx1-S) and Pfizer [...] Read more.
Background: In 2019, a new virus caused by SARS-CoV-2, called COVID-19, spread throughout the world, causing a pandemic state. As the pandemic progressed and cases continued to increase, safe vaccines were developed for the entire population. In Brazil, AstraZeneca® (ChAdOx1-S) and Pfizer® (BNT162b2) vaccines were among those administered to the population. Objectives: The objective of this study was to analyze whether immunoglobulin G (IgG) is produced for COVID-19 in individuals immunized with two doses of AstraZeneca (ChAdOx1-S) and Pfizer (BNT162b2) vaccines and to evaluate several parameters in order to understand how our bodies respond to this immunization. Methods: The study involved the participation of 120 individuals: 49 in the control group, 44 vaccinated with the AstraZeneca vaccine, and 27 the vaccinated with Pfizer vaccine. Results: Hematological, biochemical, inflammatory, and oxidant/antioxidant parameters and the production of IgG antibodies were analyzed. An increase in some inflammatory parameters was observed in vaccinated individuals, which may have been caused by an immune reaction after vaccination. In terms of hematological parameters, the changes caused by vaccination appear to be transient and quickly resolved after immunization. In terms of biochemical parameters, an increase in IgG antibodies was observed in the group vaccinated with the Pfizer® vaccine; however, the AstraZeneca® and control groups also produced IgG, although to a lesser extent. In terms of the remaining parameters, there was little change after vaccination. Regarding the levels of oxidants/antioxidants, it was observed that there was a compensation by antioxidants due to the increase in oxidant parameters, which may act as corrective mechanism. Conclusions: Both the AstraZeneca® and Pfizer® vaccines induced anti-SARS-CoV-2 IgG production, accompanied by inflammatory, hematological, and oxidative changes. Full article
(This article belongs to the Special Issue COVID and Public Health)
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17 pages, 1393 KB  
Article
Cellular Immunological Memory T Cells and IL15RA Gene Polymorphism in COVID-19 Vaccinated Individuals from Southern Brazil
by Grazielle Motta Rodrigues, Pâmela Portela da Silva, Maria Clara de Freitas Pinho, Taís da Silveira Fischer, Fernanda de Paris, Fabrício Souza Campos, Arthur Bandeira de Mello Garcia, Lucas Fernandes Jataí, Patricia Ashton-Prolla, Fernanda Sales Luiz Vianna and Clévia Rosset
Diagnostics 2026, 16(1), 89; https://doi.org/10.3390/diagnostics16010089 - 26 Dec 2025
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Abstract
Background: The development of safe and effective vaccines against SARS-CoV-2 was crucial for controlling COVID-19 and establishing long-lasting immune memory in the population. Methods: This study evaluated cellular immune memory in individuals vaccinated with different regimens in Rio Grande do Sul using flow [...] Read more.
Background: The development of safe and effective vaccines against SARS-CoV-2 was crucial for controlling COVID-19 and establishing long-lasting immune memory in the population. Methods: This study evaluated cellular immune memory in individuals vaccinated with different regimens in Rio Grande do Sul using flow cytometry. Additionally, the rs2228059 polymorphism in the IL15RA gene was genotyped. A total of 62 participants were randomly recruited. Results: A decrease in memory T cell subsets in response to SARS-CoV-2 stimuli was observed in total CD3+, CD4+, and CD8+ T cells. Regarding the timing of the last vaccine dose, 94.4% of participants had received their final COVID-19 vaccination at least two years prior to recruitment. The rs2228059 polymorphism was genotyped in 443 individuals from the Rio Grande do Sul population. Among participants who received the ChAdOx1/ChAdOx1/BNT162b2 vaccination regimen and carried the TT genotype, an increase in CD8+ naive, CD8+ effector and CD4+ naive subsets was observed in stimulated cells. Although preliminary, the results suggest no major differences between vaccination regimens. Conclusions: The progressive reduction in memory T cell counts supports the need for booster doses, which is essential not only in the context of new emerging variants but also especially to maintain adequate cellular immune protection. Full article
(This article belongs to the Special Issue Opportunities in Laboratory Medicine in the Era of Genetic Testing)
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21 pages, 4109 KB  
Article
Retrospective Cohort Analysis of Survival After SARS-CoV-2 Infection by Vaccination Status in Jamaica, April–December 2021
by Karen Webster-Kerr, Andriene Grant, Ardene Harris, Eon Campbell, Deborah Henningham, Marsha Brown, Daidre Rowe, Carol Lord, Romae Thorpe, Tanielle Mullings, Jovan Wiggan, Nicole Martin-Chen, Tonia Dawkins-Beharie and Jacqueline Duncan
Vaccines 2025, 13(12), 1250; https://doi.org/10.3390/vaccines13121250 - 17 Dec 2025
Viewed by 494
Abstract
Background/Objectives: To estimate (a) survival after SARS-CoV-2 infection by COVID-19 vaccination status, and (b) COVID-19 vaccine effectiveness in a middle-income country. Methods: In this retrospective cohort study, secondary analysis of data from the national surveillance and vaccination databases was conducted. The primary outcome [...] Read more.
Background/Objectives: To estimate (a) survival after SARS-CoV-2 infection by COVID-19 vaccination status, and (b) COVID-19 vaccine effectiveness in a middle-income country. Methods: In this retrospective cohort study, secondary analysis of data from the national surveillance and vaccination databases was conducted. The primary outcome was COVID-19 death classified based on the WHO criteria. Data were analysed by vaccination status, age, sex, geographic region, and wave period. Kaplan–Meier curves were plotted; log-rank followed by multiple comparison tests were used to compare survival probabilities. Cox proportional-hazards models with time-varying covariates estimated hazard ratios (HR). Vaccine effectiveness was computed as (1-HR) × 100. Results: A total of 55,299 COVID-19 cases were captured by the national surveillance system between 1 April and 31 December 2021. Of these, 45,774 (1581 vaccinated, 44,193 unvaccinated) were included in the analysis. After a follow-up of 327 days, there were 22 deaths (case fatality rate (CFR) 1.5%) among 1581 COVID-19 vaccinated cases and 1821 deaths (CFR 4.1%) among 44,193 unvaccinated cases. There was one COVID-19 death per 10,000 person days in vaccinated cases compared with 2.7 COVID-19 deaths per 10,000 person days in unvaccinated cases. After adjustment for age, sex, and geographic region, the effectiveness against COVID-19 death across all vaccine types (ChAdOx1 nCoV-19, BNT162b2, Ad26.COV2.S, or BBIBP-CorV) was 68% (95% CI: 51–79). Effectiveness was 75% (95% CI: 59–84) for ChAdOx1 nCoV-19. Vaccine effectiveness across all vaccine types was higher in younger cases, (82% (95% CI: 52–93), 18–64 years vs. 63% (95% CI: 41–77), ≥65 years), females (84% (95% CI: 63–93), females vs. 53% (95% CI: 24–71), males) and those vaccinated in the past 3 months (71% (95% CI: 47–85), past 0–3 months vs. 56% (95% CI: 23–75), 3–6 months). Conclusions: COVID-19 vaccines were effective in preventing COVID-19 death in a population with low vaccination coverage. Limitations of the analysis include the use of surveillance data (under-reporting of cases, missing data), exclusion of partially vaccinated cases, and insufficient data on important confounders (circulating variants and comorbidities). Full article
(This article belongs to the Special Issue Inequality in Immunization 2025)
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18 pages, 1368 KB  
Article
Vaccine Platform-Dependent Differential Impact on Microbiome Diversity: Potential Advantages of Protein Subunit Vaccines
by Hye Seong, Jin Gu Yoon, Eliel Nham, Yu Jung Choi, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Sooyeon Lim and Joon Young Song
Vaccines 2025, 13(12), 1248; https://doi.org/10.3390/vaccines13121248 - 15 Dec 2025
Viewed by 703
Abstract
Background: The COVID-19 pandemic accelerated the development of diverse vaccine platforms, including mRNA, adenoviral vector, and protein subunit vaccines. Given the growing evidence that the gut microbiome modulates vaccine-induced immunity, this study compared the effects of a protein subunit vaccine (NVX-CoV2373), an [...] Read more.
Background: The COVID-19 pandemic accelerated the development of diverse vaccine platforms, including mRNA, adenoviral vector, and protein subunit vaccines. Given the growing evidence that the gut microbiome modulates vaccine-induced immunity, this study compared the effects of a protein subunit vaccine (NVX-CoV2373), an mRNA vaccine (BNT162b2), and an adenoviral vector vaccine (ChAdOx1) on gut microbiome diversity following booster vaccination. Methods: We conducted a prospective cohort study involving 35 healthy adults who received an NVX-CoV2373 booster. Stool and blood samples were collected before vaccination and three weeks afterward. Gut microbiome profiles were analyzed using 16S rRNA gene sequencing, and the results were compared with our previous cohorts who received BNT162b2 or ChAdOx1 vaccines. Results: The NVX-CoV2373 booster was associated with a significant increase in the Shannon diversity index (p = 0.027), indicating enhanced alpha diversity. This finding contrasts with the decrease or absence of significant short-term change observed following repeated administrations of adenoviral vector and mRNA vaccines, respectively. Notably, NVX-CoV2373 vaccination was accompanied by an increased relative abundance of beneficial taxa such as Bacteroides fragilis and a decrease in Prevotella bivia. In comparison, repeated ChAdOx1 doses resulted in a sustained reduction in alpha diversity, whereas BNT162b2 showed a transient post-booster rise followed by a long-term decline in species richness. Conclusions: In the booster setting, the protein subunit vaccine NVX-CoV2373 exerted a distinct and favorable effect on gut microbiome diversity, increasing alpha diversity in contrast to the patterns observed with mRNA and adenoviral vector booster vaccines. Full article
(This article belongs to the Special Issue Human Immune Responses to Infection and Vaccination)
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12 pages, 1668 KB  
Article
Heterologous Prime-Boost with ChAdOx1-VZV Establishes Dual-Layer Immunogenicity Conferring Protective Potential Against Herpes Zoster
by Jiayu Zhao, Juan Shao, Xiuwen Sui, Menghan Wei, Xinjian Ma, Zhijun Xu and Tao Zhu
Vaccines 2025, 13(12), 1226; https://doi.org/10.3390/vaccines13121226 - 5 Dec 2025
Viewed by 556
Abstract
Background/Objectives: Varicella-zoster virus (VZV) causes herpes zoster (HZ/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8+ [...] Read more.
Background/Objectives: Varicella-zoster virus (VZV) causes herpes zoster (HZ/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8+ T-cell responses. Addressing this, we utilized the novel replication-defective chimpanzee adenovirus vector ChAdOx1 to construct the ChAdOx1-VZV (CVE) vaccine, using full-length glycoprotein E (gE) as antigen. This study evaluated the immunogenicity of a heterologous intramuscular (IM) prime/intranasal (IN) boost regimen with the aim of developing a novel VZV vaccine candidate. Methods: BALB/c mice were immunized with CVE using homologous or heterologous prime-boost regimens via IM or IN. And cynomolgus macaques were immunized intramuscularly with three doses of CVE. Cellular responses were assessed by intracellular cytokine staining (ICS) and IFN-γ ELISpot using splenocytes and PBMCs. Humoral responses were evaluated by serum gE-IgG ELISA and bone-marrow LLPC ELISpot. Memory subsets and tissue-resident T cells were analyzed by flow cytometry. Results: Heterologous IM prime/IN boost CVE regimen markedly enhanced both cellular and humoral responses, especially CD8+ T-cell responses. The induced LLPC and memory T cell responses indicate the potential for long-term protection against herpes zoster. In cynomolgus macaques, CVE induced robust serum gE-specific IgG responses and strong IFN-γ secreting T-cell activity, supporting the immunogenicity of CVE in a genetically distinct primate model and enhancing its clinical translational potential. Conclusions: CVE induces potent cellular and humoral immunogenicity, with IM prime/IN boost vaccination. Cross species immunogenicity observed in nonhuman primates further strengthens the translational relevance of this platform. These findings support CVE as a promising herpes zoster vaccine candidate and provide a rationale for continued evaluation in human-relevant systems. Full article
(This article belongs to the Special Issue Antiviral T and B Cell Immunity)
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18 pages, 1913 KB  
Article
Primary and Booster COVID-19 Vaccination in Patients with Sjögren’s Disease: Data from the Longitudinal SAFER Cohort Study
by Maressa Barbosa Beloni Lirio, Ketty Lysie Libardi Lira Machado, Olindo Assis Martins-Filho, Samira Tatiyama Miyamoto, Yasmin Gurtler Pinheiro de Oliveira, Érica Vieira Serrano, José Geraldo Mill, Karina Rosemarie Lallemand Tapia, Lunara Baptista Ferreira, Juliana Ribeiro de Oliveira, Maria da Penha Gomes Gouvea, Laura Gonçalves Rodrigues Aguiar, Barbara Oliveira Souza, Vitor Alves Cruz, Ricardo Machado Xavier, Andréa Teixeira Carvalho, Viviane Angelina de Souza, Gilda Aparecida Ferreira, Odirlei André Monticielo, Edgard Torres dos Reis Neto, Emilia Inoue Sato, Gecilmara Salviato Pileggi and Valéria Valimadd Show full author list remove Hide full author list
Vaccines 2025, 13(11), 1152; https://doi.org/10.3390/vaccines13111152 - 11 Nov 2025
Viewed by 733
Abstract
Introduction: The COVID-19 pandemic posed additional challenges for this vulnerable population, such as Sjögren’s disease (SjD), underscoring the need for effective and safe vaccination strategies. Objective: To evaluate the immunogenicity and safety of COVID-19 vaccines in patients with SjD. Methods: This prospective, observational, [...] Read more.
Introduction: The COVID-19 pandemic posed additional challenges for this vulnerable population, such as Sjögren’s disease (SjD), underscoring the need for effective and safe vaccination strategies. Objective: To evaluate the immunogenicity and safety of COVID-19 vaccines in patients with SjD. Methods: This prospective, observational, longitudinal study included SjD patients from the SAFER cohort. Immunogenicity was assessed via anti-spike IgG (IgG-S) titers using chemiluminescence reported as geometric mean titers (GMT) and fold increase in GMT (FI-GMT). Disease activity was evaluated using the ESSDAI score. Adverse events and COVID-19 infections were also monitored. Assessments were conducted at four time points: pre-first dose (T1), pre-second dose (T2), pre-booster (T3), and four weeks post-booster (T4). Primary vaccination involved ChAdOx1 nCoV-19 or inactivated vaccine (CoronaVac), and boosters were either homologous (ChAdOx1 nCoV-19) or heterologous (BNT162b2). Results: Among 51 participants (mean age 46 years; 90% female), 41% had comorbidities and 27% (n = 14/51) were highly immunosuppressed. Among those 73% (n = 37/51) under low immunosuppression, n = 8/51 (13%) were not using any medication. At baseline, 11% (n = 4/35) showed moderate/high disease activity, which decreased to 6.5% (n = 2/31) at T4. Primary vaccination was ChAdOx1 in 94% (n = 48/51) and CoronaVac in 6% (n = 3/51); 73% (n = 37/51) received heterologous and 27% (n = 14/51) homologous boosters. COVID-19 infection post-booster occurred in 20% (n = 10/51). Seroconversion rates reached nearly 100% across all medication subgroups except for biologic users, who showed delayed but stable seroconversion by T4. IgG-S titers increased progressively through T4. Primary immunization induced an ascending GMT in both vaccine types. At T4, the GMT was significantly higher in the BNT162b2 group (2148.03 [1452.05–3155.84]; p < 0.001; 95% CI) than in the ChAdOx1 group (324.29 [107.92–974.48]; p < 0.001; 95% CI); the fold-increase in immune response was six times greater with BNT162b2 (5.98 [2.97–12.03]; p = 0.001; 95% CI). Seroconversion was 100% in the heterologous group versus 83% in the homologous group (p > 0.01). Those with prior infection showed significantly higher titers, particularly at T2 and T3 (p < 0.001 for T1–T3). Adverse events were mild and not statistically significant. Multivariate regression confirmed BNT162b2 as an independent factor for higher antibody titers. Conclusion: COVID-19 vaccination in patients with SjD was safe and induced high anti-spike antibody titers and seropositivity. Heterologous boosting, particularly with BNT162b2, demonstrated superior immunogenicity. No association was found between vaccination and SjD disease flares or worsening activity. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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16 pages, 1819 KB  
Article
Immunogenicity and Safety of Half and Full Doses of Heterologous and Homologous COVID-19 Vaccine Boosters After Priming with ChAdOx1 in Adult Participants in Indonesia: A Single-Blinded Randomized Controlled Trial
by Nina Dwi Putri, Aqila Sakina Zhafira, Pratama Wicaksana, Hindra Irawan Satari, Eddy Fadlyana, Vivi Safitri, Nurlailah Nurlailah, Edwinaditya Sekar Putri, Nidya Putri, Devi Surya Iriyani, Yunita Sri Ulina, Frizka Aprilia, Evi Pratama, Indri Nethalia, Rita Yustisiana, Erlin Qur’atul Aini, Rini Fajarani, Adityo Susilo, Mulya Rahma Karyanti, Ari Prayitno, Hadyana Sukandar, Emma Watts, Nadia Mazarakis, Pretty Multihartina, Vivi Setiawaty, Krisna Nur Andriana Pangesti, Agnes Rengga Indrati, Julitasari Sundoro, Dwi Oktavia Handayani, Cissy B. Kartasasmita, Sri Rezeki Hadinegoro and Kim Mulhollandadd Show full author list remove Hide full author list
Vaccines 2025, 13(11), 1149; https://doi.org/10.3390/vaccines13111149 - 11 Nov 2025
Viewed by 655
Abstract
Background: Numerous studies have proved the efficacy of vaccination in reducing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and the coronavirus disease (COVID-19) burden. However, even though the COVID-19 vaccination coverage is high for primary doses, a booster dose is needed [...] Read more.
Background: Numerous studies have proved the efficacy of vaccination in reducing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and the coronavirus disease (COVID-19) burden. However, even though the COVID-19 vaccination coverage is high for primary doses, a booster dose is needed to sustain protection. Continuing our previous research, this study evaluates the immunogenicity and safety of full and half doses of two COVID-19 booster vaccines, ChAdOx1-S (AstraZeneca) and BNT162b2 (Pfizer-BioNTech), in individuals primed with ChAdOx1-S. Methods: This study was an observer-blind randomized controlled trial to evaluate the immunogenicity and safety of half and full doses of two COVID-19 booster vaccine types, BNT162b2 and ChAdOx1-S, among fully vaccinated, ChAdOx1-S-primed individuals in Jakarta, Indonesia. A total of 329 participants were randomized to receive either full or half doses of the booster vaccines, namely the ChAdOx1-S and BNT162b2 COVID-19 vaccines. Immunogenicity was assessed through SARS-CoV-2 antibody titers and neutralizing antibodies (NAbs) at 28 days post-booster, while safety was monitored via adverse event reporting. Results: The results showed that both vaccines demonstrated increased geometric mean titers (GMTs) post-booster. In the ChAdOx1-S booster group, at the baseline visit (day 0) and third visit (day 28), no statistically significant differences in GMT between the half- and full-dose groups were observed (p = 0.970 and 0.539, respectively). In the BNT162b2 group, no statistically significant difference was noted at the baseline visit, while the full dose was higher than the half dose at 28 days (Day 28, p = 0.011). Surrogate virus neutralization tests (sVNTs) and NAbs assays also revealed no significant differences between the half and full dose groups for both the Wuhan strain and the Delta variant. The BNT162b2 group compared to the ChAdOx1-S group revealed a statistically significant increase in IgG levels compared to ChAdOx1-S, with p-values of <0.001 and <0.001 for the half dose and full dose, respectively. This was also reflected in the NAbs test results, where BNT162b2 showed significantly higher levels against both the Wuhan strain and Delta variant. Adverse events were predominantly mild: 79.6% (n = 86/108) in the ChAdOx1-S full-dose group, 75.4% (n = 43/57) in the ChAdOx1-S half-dose group, 84.2% (n = 101/120) in the BNT162b2 full-dose group, and 92.6% (n = 88/95) in the BNT162b2 half-dose group, with pain at the injection site being the most common local reaction and myalgia and headache the most frequent systemic reactions. One serious adverse event was reported, assessed as unrelated to the vaccine. Conclusions: This study confirms that half doses of ChAdOx1-S and BNT162b2 are as immunogenic and safe as full doses, and a heterologous booster is more immunogenic than a homologous booster. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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25 pages, 2758 KB  
Article
Third Booster Half Dose of ChAdOx1-nCov-19 Is Effective, Safe, and Induces Long-Duration Humoral and Cellular Immune Response to Omicron: 1-Year Follow-Up of Viana Study
by Nésio Fernandes de Medeiros-Junior, Maria da Penha Gomes Gouvea, Luiz Antônio Bastos Camacho, Daniel Antunes Maciel Villela, Sheila Maria Barbosa de Lima, Waleska Dias Schwarcz, Adriana Souza Azevedo, Lauro Ferreira Pinto Neto, Carla Magda Allan Santos Domingues, Rosilene Nilo dos Santos Fantoni, Ludimila Forechi, Thaís Ruchdeschel, Laissa Fiorotti Albertino, Matheus Pereira, Ramon Borge Rizzi, Sara Monteiro Muniz, Hully Cantão dos Santos, Thais Luma de Oliveira Roza, Yasmin Gurtler Pinheiro de Oliveira, Laiza Hombre Dias, Samira Tatiyama Miyamoto, Karina Rosemarie Lallemand Tapia, Danielle Grillo Pacheco Lyra, Jaqueline D’Oliveira Jubini, Ana Paula Neves Burian, Isac Ribeiro Moulaz, Mia Ferreira de Araújo, Luis Fernando Lopez Tort, Any Caroline Alves de Oliveira, Roberta Oliveira Prado, Agnes Antônia Sampaio Pereira, Vitor Hugo Simões Miranda, Elaine Speziali, Christiane Costa-Pereira, Clarice Carvalho Alves, Kétyllen Reis Andrade de Carvalho, Liliane Martins dos Santos, Nani Oliveira-Carvalho, Gabriela de Oliveira, Tâmilla Mayane Alves Fidelis dos Santos, Anna Carolina Cançado Figueiredo, Ismael Artur Costa-Rocha, Ana Carolina Campi-Azevedo, Vanessa Peruhype-Magalhães, Cristiana Couto Garcia, Marilda Mendonça Siqueira, Lis Ribeiro do Valle Antonelli, Jordana Grazziela Alves Coelho-dos-Reis, Andréa Teixeira-Carvalho, José Geraldo Mill, Olindo Assis Martins-Filho and Valéria Valimadd Show full author list remove Hide full author list
Vaccines 2025, 13(11), 1113; https://doi.org/10.3390/vaccines13111113 - 30 Oct 2025
Viewed by 685
Abstract
Background: Dose-sparing approaches can be effective in maintaining immunogenicity and safety while expanding vaccine coverage. We previously demonstrated that a half dose of ChAdOx1 nCoV-19 is as effective and immunogenic for primary vaccination. Methods: This non-inferiority, non-randomized controlled trial evaluated the [...] Read more.
Background: Dose-sparing approaches can be effective in maintaining immunogenicity and safety while expanding vaccine coverage. We previously demonstrated that a half dose of ChAdOx1 nCoV-19 is as effective and immunogenic for primary vaccination. Methods: This non-inferiority, non-randomized controlled trial evaluated the effectiveness, humoral, and cellular immune responses of a third booster dose—comparing half-dose and full-dose regimens—in individuals aged 18–49 years, with a 1-year follow-up. Results: A total of 2801 participants were enrolled: 2352 received half doses and 449 received full doses. The incidence rate of COVID-19 was 225.0 per 1000 person-years in the half-dose group and 173.8 in the full-dose group, with no significant difference in effectiveness (β = −0.05; 95% CrI: −0.24 to 0.15). No deaths occurred, and hospitalization rates were similar. In a subsample (n = 558), anti-S IgG levels peaked 28 days post-dose and declined by day 180 after the primary series [175 (121–252) vs. 121 (71–208) GMT, p < 0.001], but remained elevated after the booster [192.1 (124–297) vs. 550 (380–797) GMT, p < 0.001]. Booster antibody levels were similar between groups [592.4 (318–1140) vs. 550 (380–797) GMT]. The half-dose group showed high titers against Omicron and robust T/B-cell responses (e.g., EMCD4, EMCD8, IFN+CD4+, CD19+TNF+). Conclusions: Fractional half dose of ChAdOx nCov-19 was effective and non-inferior to a full booster dose. Homologous regimen with 3 half doses or 3 full doses induced a similar increase in antibody titers and robust cellular response. ClinicalTrials.gov (NCT05059106). Full article
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7 pages, 210 KB  
Case Report
Observations of Wart Clearance Following COVID-19 Vaccination: Coincidence or Missed Immunologic Signals?
by Qiwei Wilton Sun, Caroline A. Nelson and Howard P. Forman
Vaccines 2025, 13(11), 1081; https://doi.org/10.3390/vaccines13111081 - 22 Oct 2025
Viewed by 1174
Abstract
Background/Objectives: The COVID-19 vaccines have been extensively studied for their potential adverse side effects. However, reports of unexpected but potentially beneficial immune responses have received comparatively less attention. Methods: In this case series, a PubMed search was conducted using the terms “warts”, “verruca”, [...] Read more.
Background/Objectives: The COVID-19 vaccines have been extensively studied for their potential adverse side effects. However, reports of unexpected but potentially beneficial immune responses have received comparatively less attention. Methods: In this case series, a PubMed search was conducted using the terms “warts”, “verruca”, “HPV”, “COVID-19”, “SARS-CoV-2”, “immunization”, and “vaccination.” All reported cases of wart clearance temporally linked to COVID-19 vaccination were identified and summarized, including patient demographics, vaccine type, number of doses, timing of clearance, and follow-up duration. Results: Five cases were identified. Patients varied in age, sex, comorbidity, and immunologic status. Warts were long-standing and treatment-resistant in all cases. Clearance occurred within approximately 2–4 weeks following the second or third vaccine dose (either mRNA-based [BNT162b2, mRNA-1273] or adenoviral vector [ChAdOx1-S]) and was sustained for 2–8 months of follow-up with no recurrences reported. Conclusions: While causality cannot be determined, the convergence of reports across diverse patients, consistent timing of clearance, and plausible immunologic pathways suggest that COVID-19 vaccination may, in rare instances, trigger beneficial immune activation against HPV-infected keratinocytes. Recognition of such unexpected outcomes underscores the need for broader vaccine safety and efficacy surveillance that includes both adverse and beneficial immune effects. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
17 pages, 574 KB  
Article
Impact of SARS-CoV-2 Vaccination on Disease Activity and Severity of COVID-19 Infection in Patients with Systemic Lupus Erythematosus: A Multicenter Cohort Study
by Natália Sarzi Sartori, Ketty Lysie Libardi Lira Machado, Samira Tatiyama Miyamoto, Flavia Zon Pretti, Maria da Penha Gomes Gouveia, Yasmin Gurtler Pinheiro de Oliveira, Vanezia Gonçalves da Silva, Filipe Faé, Ana Paula Neves Burian, Karina Rosemarie Lallemand Tapia, Anna Carolina Simões Moulin, Luiza Lorenzoni Grillo, Paula dos Santos Athayde, Helena da Silva Corona, Sabrina de Souza Ramos, Flávia Maria Matos Melo Campos Peixoto, Priscila Dias Cardoso Ribeiro, Vanessa de Oliveira Magalhães, Mariana Freitas de Aguiar, Erika Biegelmeyer, Cristiane Kayser, Alexandre Wagner Silva De Souza, Charlles Heldan de Moura Castro, Juliana Bühring, Sandra Lúcia Euzébio Ribeiro, Sérgio Henrique Oliveira dos Santos, Clara Pinheiro Martins, Jonathan Willian da Silva Rodrigues, Marcos Mavignier Sousa Dias, Bruna Guimarães Dutra, Camila Maria Paiva França Telles, Samuel Elias Basualto Dias, Rodrigo Poubel Vieira de Rezende, Katia Lino Baptista, Rodrigo Cutrim Gaudio, Ana Karla Guedes de Melo, Valéria Bezerra da Silva, Vitor Alves Cruz, Jozelia Rêgo, Rejane Maria Rodrigues de Abreu Vieira, Adah Sophia Rodrigues Vieira, Adriana Maria Kakehasi, Anna Carolina Faria Moreira Gomes Tavares, Artur José Azevedo Pereira, Pollyana Vitoria Thomaz da Costa, Valderilio Feijó Azevedo, Nicole Pamplona Bueno de Andrade, Guilherme Levi Tres, Olindo Assis Martins-Filho, Vanessa Peruhype-Magalhães, Valéria Valim, Gilda Aparecida Ferreira, Andréa Teixeira-Carvalho, Edgard Torres dos Reis-Neto, Emilia Inoue Sato, Marcelo de Medeiros Pinheiro, Viviane Angelina de Souza, Ricardo Machado Xavier, Gecilmara Salviato Pileggi and Odirlei André Monticieloadd Show full author list remove Hide full author list
Vaccines 2025, 13(10), 1074; https://doi.org/10.3390/vaccines13101074 - 21 Oct 2025
Viewed by 953
Abstract
Background: To prospectively evaluate the safety and clinical impact of SARS-CoV-2 vaccines in patients with systemic lupus erythematosus (SLE). Methods: Subanalysis of the Brazilian multicenter observational study “Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Inflammatory Diseases [...] Read more.
Background: To prospectively evaluate the safety and clinical impact of SARS-CoV-2 vaccines in patients with systemic lupus erythematosus (SLE). Methods: Subanalysis of the Brazilian multicenter observational study “Safety, Effectiveness and Duration of Immunity after Vaccination against SARS-CoV-2 in Patients with Immune-Mediated Inflammatory Diseases (SAFER)”, which included SLE patients vaccinated with CoronaVac, ChAdOx1, or BNT162b2. Patients with HIV infection, pregnant women, or those with immunosuppression not related to SLE were excluded. Safety data related to adverse events and underlying disease activity were assessed. Additionally, COVID-19 cases were monitored throughout the follow-up period. Results: The study included 373 patients with systemic lupus erythematosus (SLE), with a mean age of 36 years, the majority being women (89.8%). The most common adverse events after SARS-CoV-2 vaccination were injection site reactions and headache, observed both after the first and subsequent doses. The ChAdOx-1 vaccine was associated with a higher frequency of adverse events compared to CoronaVac. At baseline, 38.3% of patients were in remission, 32.8% had low disease activity, and 28.9% had moderate to high activity. Following CoronaVac vaccination, there was an increase in remission rates (from 34.6% to 51.1%) and a significant reduction in moderate to high activity (from 37.6% to 15.0%) after the first dose, with this reduction partially maintained after the second dose. In contrast, patients vaccinated with ChAdOx-1 showed an increase in moderate to high activity (from 14.5% to 38.2% after the first dose), a trend that persisted after the second dose. No statistically significant changes in disease activity were observed among those who received BNT162b2. During follow-up, 44 cases of COVID-19 were reported, all mild, with no deaths or need for intensive care unit admission. Conclusions: Vaccination against SARS-CoV-2 demonstrated a favorable safety profile in patients with SLE, with a low frequency of serious adverse events. While analysis of disease activity revealed variations across vaccine platforms, most notably an increased proportion of moderate to high disease activity among those receiving ChAdOx-1 compared with CoronaVac and BNT162b2, the overall occurrence of COVID-19 during follow-up was limited to mild cases, with no severe outcomes. These findings highlight that, despite potential risks of disease exacerbation, the clear protection against severe COVID-19 supports vaccination as a beneficial strategy for this immunocompromised population. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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17 pages, 2163 KB  
Article
Immunogenicity and Breakthrough Outcomes of mRNA Booster Strategies Among Healthcare Workers During the BA.1/BA.2 Omicron Surge
by Song Mi Moon, Jung Nam An, Jae Hyun Kwon, Sung Gyun Kim and Han Wool Kim
Microorganisms 2025, 13(10), 2362; https://doi.org/10.3390/microorganisms13102362 - 14 Oct 2025
Viewed by 498
Abstract
Throughout the 2019 coronavirus disease pandemic, various vaccine regimens were implemented. Real-world data comparing their effectiveness during the BA.1/BA.2 Omicron wave remain limited. We prospectively enrolled healthcare workers who had completed two doses of mRNA or ChAdOx1 (A) vaccine and received an mRNA [...] Read more.
Throughout the 2019 coronavirus disease pandemic, various vaccine regimens were implemented. Real-world data comparing their effectiveness during the BA.1/BA.2 Omicron wave remain limited. We prospectively enrolled healthcare workers who had completed two doses of mRNA or ChAdOx1 (A) vaccine and received an mRNA vaccine booster (BNT162b2 (P) or mRNA-1273 (M)). Neutralizing antibody levels were measured 6 months after the primary vaccinations and 1 month post-booster vaccination using a surrogate virus neutralization assay. Breakthrough infections were identified through institutional surveillance and the national reporting system. Among 318 participants (P-P-P: 71; A-A-P: 205; A-P-P: 19; M-M-M: 23), pre-booster neutralizing activity was lowest in the ChAdOx1-primed groups. One month post-booster vaccination, the neutralizing activity exceeded 97% across all regimens. The cumulative incidence of breakthrough infection varied significantly from 43.7% (P-P-P) to 84.2% (A-P-P). In adjusted Cox models, A-P-P showed the highest infection risk (HR 2.99, 95% CI 1.65–5.42). In summary, mRNA boosters restored neutralizing activity, but during the early BA.1/BA.2 Omicron wave they were less effective in preventing infections regardless of disease severity. Therefore, antibody titers alone are insufficient for evaluating protection, underscoring the need for continuous monitoring to support timely policy decisions during epidemic surges. Full article
(This article belongs to the Special Issue SARS-CoV-2: Infection, Transmission, and Prevention)
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14 pages, 1305 KB  
Article
Serological Response to COVID-19 Vaccination in Saudi Arabia: A Comparative Study of IgG and Neutralising Antibodies Across Vaccine Platforms
by Mariam M. AlEissa, Ahdab A. Alsaieedi, Reema Alduaiji, Fahad Almsned, Yousif AlDossary, Nada Saleh, Raghad A. AlQurashi, Esraa A. Hawsa, Muath b Ben Shaded, Amer M. Alshehri, Osamah T. Khojah, Eyad Y. Abu Sarhan, Hamad H. Alonazi, Walid A. Nouh, Khalid H. AlAnazi, Sami S. Almudrra, Khaled I. AlAbdulkareem, Abdullah AlJurayyan and Abdullah M. Asiri
Vaccines 2025, 13(10), 1042; https://doi.org/10.3390/vaccines13101042 - 10 Oct 2025
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Abstract
Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) [...] Read more.
Background: In the Kingdom of Saudi Arabia, various COVID-19 vaccines were administered during the pandemic. However, region-specific real-word comparative data on their immunogenicity remain limited. This study aimed to assess the serological responses to Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and AstraZeneca (ChAdOx1 nCoV-19) vaccines in a diverse population living in KSA. Methods: This observational study included 236 adults recruited from vaccination sites in Riyadh. Participants provided serum samples at predefined intervals: before the first dose, after the first dose, after the second dose, and post-vaccination infection (if applicable). IgG and neutralising antibodies were quantified using ELISA assays. Demographic and vaccination data, and their associations with antibody responses, were evaluated. Results: At baseline, 75.4% of participants were positive for SARS-CoV-2 IgG, suggesting high prior exposure. Marked incremental increases in IgG levels were observed after each vaccine dose. Both Moderna and Pfizer elicited stronger responses, with Pfizer inducing the strongest early response and Moderna achieving the highest overall titres. Among IgG-positive individuals, neutralising antibodies were detected in 98.1%. There were no statistically significant differences by age or gender, although males tended to show higher mean titres. Heterologous vaccine schedules induced comparable or enhanced immunogenicity relative to homologous schedules, supporting their use in flexible immunisation strategies. Conclusions: All COVID-19 vaccines administered in Saudi Arabia elicited robust antibody responses, particularly the mRNA-based vaccines. Our findings support their continued use and justify varied vaccination approaches, including mix-and-match booster strategies, to enhance community immunity. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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23 pages, 1632 KB  
Review
Retinal Vascular Occlusion Following COVID-19 Vaccination: A Comprehensive Review of Observational Study and Pathophysiological Mechanisms
by Yuchen Zhang, Haoliang Zhang, Kangjia Lv, Xin Lin, Feng’e Chen, Hui Cao and Chong Chen
Vaccines 2025, 13(7), 733; https://doi.org/10.3390/vaccines13070733 - 7 Jul 2025
Viewed by 3616
Abstract
Background: Retinal vascular occlusion (RVO) and retinal artery occlusion (RAO) have been reported as rare adverse events following COVID-19 vaccination, raising concerns about vaccine safety. This review synthesizes cohort and case–control studies assessing the association between COVID-19 vaccines and RVO/RAO, while exploring [...] Read more.
Background: Retinal vascular occlusion (RVO) and retinal artery occlusion (RAO) have been reported as rare adverse events following COVID-19 vaccination, raising concerns about vaccine safety. This review synthesizes cohort and case–control studies assessing the association between COVID-19 vaccines and RVO/RAO, while exploring potential pathophysiological mechanisms. Methods: We analyzed large-scale population-based studies from South Korea, Europe, and the TriNetX database, focusing on odds ratios (OR), hazard ratios (HR), and relative risks (RR) across mRNA and adenoviral vector vaccines. Pathological processes were hypothesized based on molecular and clinical evidence. Results: Studies investigating the association between COVID-19 vaccination and retinal vascular occlusion show conflicting results; some studies report no association (e.g., OR 0.93, 95% CI 0.60–1.45), others suggest reduced risk (e.g., OR 0.80, 95% CI 0.64–0.99), and one indicates increased risk over two years (HR 2.19, 95% CI 2.00–2.39). Adenoviral vector vaccines, particularly ChAdOx1, show higher RAO incidence in specific cohorts. Proposed mechanisms include vaccine-induced immune thrombotic thrombocytopenia (VITT) via anti-PF4 antibodies, spike protein-mediated endothelial dysfunction, and adjuvant-driven inflammation. Conclusions: While causality remains unproven, temporal heterogeneity and vaccine type-specific risks warrant further investigation. Longitudinal studies with robust controls are needed to clarify these associations in the post-pandemic context. Full article
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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32 pages, 4906 KB  
Article
Transcriptomic and miRNA Signatures of ChAdOx1 nCoV-19 Vaccine Response Using Machine Learning
by Jinting Lin, Qinglan Ma, Lei Chen, Wei Guo, Kaiyan Feng, Tao Huang and Yu-Dong Cai
Life 2025, 15(6), 981; https://doi.org/10.3390/life15060981 - 18 Jun 2025
Viewed by 1130
Abstract
Vaccination with ChAdOx1 nCoV-19 is an important countermeasure to fight the COVID-19 pandemic. This vaccine enhances human immunoprotection against SARS-CoV-2 by inducing an immune response against the SARS-CoV-2 S protein. However, the immune-related genes induced by vaccination remain to be identified. This study [...] Read more.
Vaccination with ChAdOx1 nCoV-19 is an important countermeasure to fight the COVID-19 pandemic. This vaccine enhances human immunoprotection against SARS-CoV-2 by inducing an immune response against the SARS-CoV-2 S protein. However, the immune-related genes induced by vaccination remain to be identified. This study employs feature ranking algorithms, an incremental feature selection method, and classification algorithms to analyze transcriptomic data from an experimental group vaccinated with the ChAdOx1 nCoV-19 vaccine and a control group vaccinated with the MenACWY meningococcal vaccine. According to different time points, vaccination status, and SARS-CoV-2 infection status, the transcriptomic data was divided into five groups, including a pre-vaccination group, ChAdOx1-onset group, MenACWY-onset group, ChAdOx1-7D group, and MenACWY-7D group. Each group contained samples with 13,383 RNA features and 1662 small RNA features. The results identified key genes that could indicate the efficacy of the ChAdOx1 nCoV-19 vaccine, and a classifier was developed to classify samples into the above groups. Additionally, effective classification rules were established to distinguish between different vaccination statuses. It was found that subjects vaccinated with ChAdOx1 nCoV-19 vaccine and infected with SARS-CoV-2 were characterized by up-regulation of HIST1H3G expression and down-regulation of CASP10 expression. In addition, IGHG1, FOXM1, and CASP10 genes were strongly associated with ChAdOx1 nCoV-19 vaccine efficacy. Compared with previous omics-driven studies, the machine learning algorithms used in this study were able to analyze transcriptome data faster and more comprehensively to identify potential markers associated with vaccine effect and investigate ChAdOx1 nCoV-19 vaccine-induced gene expression changes. These observations contribute to an understanding of the immune protection and inflammatory responses induced by the ChAdOx1 nCoV-19 vaccine during symptomatic episodes and provide a rationale for improving vaccine efficacy. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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26 pages, 6162 KB  
Article
Ethnic Comparisons of Spike-Specific CD4+ T Cells, Serological Responses, and Neutralizing Antibody Titers Against SARS-CoV-2 Variants
by Fani Pantouli, Vanessa Silva-Moraes and Ted M. Ross
Vaccines 2025, 13(6), 607; https://doi.org/10.3390/vaccines13060607 - 4 Jun 2025
Viewed by 1746
Abstract
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, [...] Read more.
Background/Objectives: To evaluate how immune responses compare among ethnic groups approximately 2 years after receiving a third dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1or BBIBP-CorV), we tested T cell responses and Spike-specific RBD-antibody titer, and neutralized antibody titer levels utilizing Spectral Flow cytometry, ELISA, and SARS-CoV-2 pseudotyped-based neutralization assays, respectively. Methods: Forty-four individuals from January–December 2023 were identified within the cohort and were classified into different ethnic backgrounds; Black (N = 13), Asian (N = 14), Caucasian (N = 17). We recognize that the “Asian” group includes diverse subpopulations with distinct genetic and environmental backgrounds, which could not be further stratified due to sample-size limitations. Spike-specific AIM+, CD4+, and CD8+ T cell responses were assessed and evaluated against SARS-CoV-2 variants, including the ancestral Wuhan, Delta, and multiple Omicron subvariants (B1.1529, BA2.86, BA.4/5, and XBB.1). Alongside we tested the RBD-IgG and neutralizing antibody titers against the ancestral Wuhan. Spearman’s correlation analysis was utilized to determine corelative relationships among the AIM+ and CD4+ T cell responses, as well as the RBD-IgG and neutralizing antibody titers. Results: Our results show robust and comparable RBD-IgG and neutralizing antibody titers across all groups, with a significant positive correlation between these two measurements. Significant differences were observed in T-cell activation, with Asian participants exhibiting lower frequencies of Spike-specific CD4+ T cells against SARS-CoV-2 Omicron subvariants and higher frequencies of cytokine-producing CD4+ T cells (TNF-α, IFN-γ, and IL-2) as compared to the Caucasian group. Breakthrough infection status was not fully controlled and may influence these findings. Conclusion: Despite a small sample size and potential confounding by natural infections within our long-time-span sampling, our data suggest persistent cellular and humoral immunity 2 years after vaccination across ethnicities, with notable differences in T cell activation and cytokine profile. These preliminary observations highlight the need for larger, more detailed studies that consider intra-ethnic diversity and hybrid immunity to better understand ethnic differences in COVID-19 vaccine responses. Full article
(This article belongs to the Special Issue 3rd Edition: Safety and Autoimmune Response to SARS-CoV-2 Vaccination)
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