Search Results (871)

Background: COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally licensed COVID-19 vaccines. Methods: The potential public health and economic impact of mRNA-1283 in adults ≥ 60 years and high-risk adults aged 18–59 years was modeled versus no vaccination and originally licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with a 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination and price premiums over existing vaccines were determined at a willingness-to-pay threshold of €50,000/quality-adjusted life-year (QALY) gained. Results: Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations, and 5300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5400 hospitalizations, and 1200 deaths, saving 9667 QALYs and over €66.5 million in treatment costs. The EJP was €238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1309 and 1679 hospitalizations, respectively) and was cost-effective at an incremental EJP of €62 versus mRNA-1273 and €80 versus BNT162b2. Conclusions: The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs. Full article

People with HIV (PWH) may exhibit altered immune responses to SARS-CoV-2 vaccination due to persistent immune dysregulation despite antiretroviral therapy. We evaluated humoral immunogenicity following mRNA SARS-CoV-2 vaccination in PWH according to CD4 T-cell count and compared responses with HIV-negative controls. The study included 57 PWH stratified by CD4 count (<200 and ≥200 cells/µL), alongside 12 HIV-negative controls. Neutralizing antibody titers (NT50) against SARS-CoV-2 pseudoviruses expressing the D614G and Omicron BA.5 spike variants were measured using a luciferase-based neutralization assay one month (M1) and six months (M6) after primary vaccination with BNT162b2 or mRNA-1273. PWH with CD4 counts ≥ 200 cells/µL demonstrated higher neutralizing titers against D614G at M1 and M6, with significant differences observed between CD4 groups (M1: p = 0.03; M6: p = 0.02). Neutralization of BA.5 was lower overall; while no overall group differences were observed at M1, higher titers were detected among individuals with CD4 ≥ 200 cells/µL at six months (p = 0.04). Neutralizing titers correlated positively with CD4 counts among PWH. Responses were broadly comparable between PWH and HIV-negative controls and did not differ substantially by vaccine type. These findings indicate that immune status, reflected by CD4 T-cell count, is a key determinant of SARS-CoV-2 vaccine-induced humoral responses in PWH and support prioritizing vaccination strategies for individuals with advanced immunosuppression. Full article

Background/Objectives: This study evaluated the Omicron LP.8.1 variant-adapted BNT162b2 mRNA vaccine (LP.8.1-adapted BNT162b2). Methods: This analysis is part of an ongoing phase 3 open-label study evaluating the immunogenicity, safety, and tolerability of LP.8.1-adapted BNT162b2. Reported here are descriptive 2-week post-vaccination results in 18–64 -year-olds at high risk of severe COVID-19 and in ≥65-year-olds who received the Omicron KP.2-adapted COVID-19 vaccine ≥ 6 months previously. Primary immunogenicity endpoints included neutralizing antibody geometric mean titers (GMTs) against LP.8.1 and KP.2 at 2 weeks after vaccination and geometric mean fold rises from baseline to 2 weeks after vaccination. Results were compared with a historical control group of adults who received KP.2-adapted BNT162b2 in a previous study. Tolerability and safety were also assessed. Results: Overall, 104 participants received LP.8.1-adapted BNT162b2 (18–64-year-olds, n = 51; ≥65-year-olds, n = 53). Baseline neutralizing GMTs were higher in LP.8.1-adapted BNT162b2 recipients than in the historical control group of KP.2-adapted BNT162b2 recipients against both sublineages (248 vs. 157 against LP.8.1; 372 vs. 187 against KP.2). Serum-neutralizing LP.8.1 and KP.2 GMTs increased 2 weeks after vaccination with LP.8.1-adapted BNT162b2 (1752 against LP.8.1; 2104 against KP.2) and historical control groups (1555 and 2395, respectively), and across both age groups. Reactogenicity events with LP.8.1-adapted BNT162b2 were generally mild or moderate and occurred at generally similar frequencies in both age groups. Adverse events were reported in 4.8% of participants (all in 18–64-year-olds); no serious adverse events were reported. Conclusions: After 2 weeks of follow-up, and in a small sample size, LP.8.1-adapted BNT162b2 was immunogenic in ≥65-year-olds and ≥18-year-olds at high risk of severe COVID-19. The safety and tolerability profile for LP.8.1-adapted BNT162b2 was consistent with the current US prescribing information for BNT162b2 and that of other variant-adapted BNT162b2 vaccines (Clinicaltrials.gov Identifier: NCT07069309, registered 16 July 2025). Full article

Background/Objectives: Our previous study demonstrated that while the third SARS-CoV-2 booster effectively enhanced immunity against the Delta subvariant, its protection declined over time. This study aimed to evaluate and compare the humoral and cellular immune responses, as well as reactogenicity, of the mRNA-1273 vaccine administered as a fourth booster in healthy Thai adults previously vaccinated with two doses of CoronaVac (CV) followed by a third dose of either AZD1222 (AZ) or BNT162b2 (BNT). Methods: Participants received a single 100 µg (0.5 mL) intramuscular dose of mRNA-1273. Blood samples were collected at baseline (D0), D14, D90, and D180 to assess anti-RBD IgG, conduct a surrogate virus neutralization test (sVNT) against the Delta and Omicron variants, and assess IFN-γ levels and reactogenicity. Results: Both 2CV/AZ- and 2CV/BNT-primed groups exhibited comparable local and systemic reactogenicity. The fourth mRNA-1273 dose markedly increased Delta variant inhibition within 14 days in both groups and remained at high levels at Days 90 and 180. sVNT inhibition against Omicron rose similarly in both groups at Day 14; it declined sharply by Days 90 and 180, with the 2CV/AZ-primed group showing significantly lower levels than the 2CV/BNT-primed group. Baseline anti-RBD IgG levels were lower in the 2CV/AZ group (p = 0.003) but surpassed those of the 2CV/BNT group by Day 14, with no significant differences at later time points. IFN-γ responses followed a similar pattern to anti-RBD IgG Conclusions: A heterologous fourth mRNA-1273 booster in both 2CV/AZ- and 2CV/BNT-primed groups effectively enhances B-cell and T-cell responses against SARS-CoV-2. However, emerging variants such as Omicron may still pose challenges. The trial was registered with the Thai Clinical Trials Registry: the name of the registry: “The comparison of immune response to the 4th dose booster with mRNA-1273 COVID-19 vaccine in individuals who had received 2 doses of CoronaVac and booster with ChAdOx-1 or BNT162b2 COVID-19 vaccine”, TCTR20220205002 on 5 February 2022. Full article

Background/Objectives: Understanding the relationship between reactogenicity and immunogenicity after repeated BNT162b2 vaccination is critical for optimizing vaccination strategies. This study quantified their progressive dissociation across four vaccine doses. Methods: We conducted a prospective longitudinal cohort study among Croatian healthcare workers vaccinated with BNT162b2 from January 2021 to January 2024. Anti-SARS-CoV-2 IgG antibodies were measured at 16 timepoints using chemiluminescent immunoassay. Local (pain, erythema, swelling) and systemic (fever, fatigue, headache, myalgia, arthralgia, nausea) reactions were recorded for 7 days using FDA toxicity scale. Correlations were analyzed with Spearman’s method and Bonferroni correction. Fourth-dose responses were predicted by exponential modeling. Results: Of 631 participants, 524 completed primary immunization, 418 received a third dose (173 with complete data), and 56 received a fourth dose (22 with complete paired data). Local reactions declined from 82.4% after the first dose to 42.9% after the fourth (p < 0.001). Systemic reactions peaked at 44.8% after the second dose, then decreased to 26.0% after the third and 19.6% after the fourth. In contrast, median antibody levels rose from 9910 AU/mL after the primary series to 29,002 AU/mL after the third and 38,274 AU/mL after the fourth. Correlations between reactions and antibody titer progressively weakened: r = 0.37 (95% CI 0.29–0.44, p < 0.001) after the primary series, r = 0.08 (95% CI −0.07 to 0.23, p = 0.30) after the third, and r = 0.04 (95% CI −0.39 to 0.45, p = 0.86) after the fourth dose. Conclusions: Progressive dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 doses. Booster doses maintain robust antibody responses despite reduced reactogenicity, reinforcing that minimal side effects are consistent with sustained humoral responses. Full article

Background/Objectives: Guillain–Barré syndrome (GBS) is a rare but serious immune-mediated neurological disorder monitored as an adverse event of special interest during the COVID-19 pandemic. This study aimed to estimate the incidence of GBS following COVID-19 vaccination and SARS-CoV-2 infection and to compare the risk by vaccine platform. Methods: We conducted a population-based retrospective cohort study using data from the Valencia Health System Integrated Database (Spain) between January 2018 and March 2022. Two cohorts were defined: individuals receiving COVID-19 vaccines (mRNA-based vaccines (BNT162b2 [Pfizer–BioNTech] and mRNA-1273 [Moderna]) or non-virus-vectored (NVV) adenoviral vector-based vaccines (ChAdOx1-S [AstraZeneca] and Ad26.COV2.S [Janssen])) and individuals with laboratory-confirmed SARS-CoV-2 infection. Incident GBS cases were identified within a predefined 42-day risk window following vaccination or infection. Incidence rates were calculated per 100,000 vaccine doses administered or SARS-CoV-2 infections. Results: Among 5,109,919 individuals, 4,270,610 received at least one COVID-19 vaccine dose and 920,643 experienced at least one SARS-CoV-2 infection. A total of 69 GBS cases occurred within 42 days following vaccination (incidence: 0.67 per 100,000 doses), whereas 21 cases occurred after infection (incidence: 2.20 per 100,000 infections). Incidence was lower after mRNA-based vaccines (0.55 per 100,000 doses) than after NVV vaccines (1.57 per 100,000 doses). Conclusions: This study confirms that GBS occurrence following vaccination is rare. The incidence is lower among individuals who received mRNA vaccines compared to those who received NVV vaccines. Moreover, GBS appears to be more frequent after a COVID-19 infection than after vaccination. These findings highlight the importance of integrating pharmacoepidemiological analyses with pharmacovigilance data to contextualize rare but serious adverse events. Full article

COVID-19 mRNA vaccines activate type I interferon pathways and in genetically or immunologically predisposed individuals may trigger autoimmune responses, including autoantibodies against melanoma differentiation-associated protein 5 (MDA5). Although cases of dermatomyositis (DM), particularly anti-MDA5-positive DM, have been increasingly reported after SARS-CoV-2 vaccination, its clinical spectrum and management remain incompletely defined. We conducted a narrative review of the literature on post-vaccination dermatomyositis, focusing on clinical features, autoantibody profiles, therapeutic approaches, and outcomes. The review was enriched by the inclusion of a new case: a 60-year-old woman who developed anti-MDA5-positive dermatomyositis two weeks after receiving her fourth dose of the BNT162b2 (Pfizer/BioNTech) vaccine. She presented predominantly with cutaneous and articular manifestations in the absence of interstitial lung disease. Treatment with oral prednisone, intravenous alprostadil, and the Janus kinase inhibitor tofacitinib resulted in marked clinical improvement. This case, together with the literature review, illustrates both typical and atypical presentations of vaccine-associated anti-MDA5 DM, highlights diagnostic challenges without lung involvement, and suggests JAK inhibition as a potential therapeutic option, contributing to a more comprehensive understanding of post-vaccination dermatomyositis. Full article

The prompt and extensive use of COVID-19 vaccines has dramatically reduced both cases and casualties, but it has also underscored a number of critical issues that need to be addressed for their full exploitation at global level. This Special Issue was launched to gather fresh data to improve the way we use vaccines that are currently available to contribute to the design and the development of new ones and to elucidate social, ethical and psychological concerns that might hamper vaccine acceptance and use. It includes 15 articles six of which address, under various aspects, the level and durability of protective immunity; five deal with the highly debated field of vaccine use, efficacy and safety, in persons with an impaired/dysregulated immune system; one paper reports on adjuvants’ role in immune stimulation; one on the interference of natural adenovirus immunity with DNA vaccine response; one is a review on the cellular mechanisms of vaccine-dependent myocarditis; and one explores social attitudes to vaccines in different ethnic groups during early phases of the pandemic. Far from being complete and exhaustive, this Special Issue provides the reader with fresh insights into several critical questions raised by or connected to the advent of COVID-19 vaccines. This introductory article provides an overview of their contribution, while offering a quick glance at the current state of the art. Full article

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

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

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

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

Background/Objectives: Paediatricians’ recommendations influence parental decisions to vaccinate their children. On 19 January 2022, the World Health Organization authorized the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) under Emergency Use Listing for children under 12 years as a measure to mitigate disease spread and direct protection for children with underlying conditions. We assessed knowledge, attitudes, and practices (KAP) of Palestinian paediatricians regarding COVID-19 vaccination for children under 12 years and identified factors affecting support for vaccination. Methods: From 1 October to 8 November 2023, we surveyed paediatricians across the West Bank using structured telephone interviews. We collected data on sociodemographic characteristics and KAP regarding COVID-19 vaccination and calculated KAP scores from eight, nine, and nine items, respectively, with total scores categorized as poor/moderate/good. We performed bivariable and multivariable analyses to identify factors associated with paediatricians supporting COVID-19 vaccination for children under 12 years. Results: Of the 367 eligible paediatricians, 323 (88%) responded; the median age was 51 years (range: 28–70); 27% supported COVID-19 vaccination for children. Mean scores for knowledge (range 0–8), attitude (0–9), and practice (0–9) were 3.0 ± 2.1, 3.9 ± 2.4, and 4.0 ± 1.7, respectively. The mean overall KAP score (0–26) was 11 ± 4.8. Safety and efficacy concerns and lack of long-term data were the main reasons for hesitancy. Higher knowledge scores (PR = 1.8, 95% CI: 1.3–2.5, p = 0.001) and positive attitudes (PR = 1.6, 95% CI: 1.1–2.3, p = 0.01) were significantly associated with paediatricians’ support for vaccination. After adjustment for other factors, participants with regular continuing medical education attendance (aPR = 1.4, 95% CI: 1.0–2.6, p = 0.045), trusting WHO recommendations (aPR = 3.1, 95% CI: 1.4–7.8, p = 0.047), having a positive attitude score (aPR = 1.3, 95% CI: 0.4–4.4, p = 0.041), and a good total KAP score (aPR = 1.1, 95% CI: 1.0–1.2, p = 0.044) supported COVID-19 vaccination for children. Conclusions: Support for COVID-19 vaccination among Palestinian paediatricians was low, associated with their knowledge, attitudes, and trust in health authorities. The revised WHO recommendations from 10 November 2023, decreasing the priority of vaccinating healthy children, could influence the opinion of paediatricians. However, the low support for COVID-19 vaccinations could affect the performance of other vaccination programmes and should be carefully addressed through targeted education. Full article

Background: Healthcare workers (HCWs) are at high risk of breakthrough SARS-CoV-2 infections despite complete vaccination schedules. There are gaps in our understanding of the specific antibody isotypes and cytokine profiles produced during an infection following vaccination. In this study, we evaluated SARS-CoV-2⁻specific antibody isotypes and their association with cytokine production in HCWs with breakthrough infections. Methods: Serum samples from 114 HCWs were analyzed for antibody isotypes against the nucleoprotein (NCP) and the receptor binding domain (RBD) of the spike protein, as well as for a panel of 13 cytokines. Results: Vaccinated SARS-CoV-2⁺ HCWs showed a higher prevalence of anti-SARS-CoV-2 antibodies against NCP (IgM = 93.8%, IgG = 93.8%, IgA = 28.1%) and RBD (IgM = 46.9%, IgG = 100%, IgA = 90.6%). A specific IgM response to NCP was more frequent in vaccinated SARS-CoV-2⁺ individuals, whereas IgA responses were predominantly specific for RBD. Both pro- and anti-inflammatory cytokines were elevated in vaccinated HCWs with breakthrough infections compared with unvaccinated and uninfected individuals. Interestingly, infected IgG+ HCWs with IgM specific for both NCP and RBD exhibited significantly higher IL-8, IL-6, TNF-α, IFN-γ, IL-2, IL-10, and TGF-β concentrations. Conclusion. Our data show that breakthrough infections in vaccinated HCWs induce a robust pro-and anti-inflammatory cytokine profile, which is associated with a broader IgM response directed against both NCP and RBD. Full article