Search Results (139)

Background/Objectives: Vaccine immunogenicity is often suboptimal in vulnerable populations such as the elderly, infants, and individuals in low- and middle-income countries. One contributing factor may be pre-existing immunomodulatory conditions, including helminth infections. This study investigates the impact of Fasciola hepatica (F. hepatica) derived molecules on the early humoral response to the COVID-19 mRNA vaccine Comirnaty^® in a mouse model. Methods: BALB/c mice were pretreated with a F. hepatica protein extract (FH) or complete Freund’s adjuvant (CFA) prior to vaccination. Cytokine production and antibody responses were assessed at 0, 14, and 21 days post-vaccination (dpv) through serum analysis and ex vivo splenocyte stimulation with the SARS-CoV-2 receptor-binding domain (RBD) or LPS. Results: At 0 dpv, FH-treated mice showed increased serum IL-10, while CFA treatment induced IL-12. FH- but not CFA-treated splenocytes secreted IL-10 upon RBD or LPS stimulation. At 21 dpv, FH-treated mice lacked IFN-γ production but maintained IL-10 and showed elevated IL-4, consistent with a Th2-skewed profile. Although total anti-RBD IgG levels were similar between groups, FH-treated mice exhibited reduced IgG avidity and a higher IgG1/IgG2 ratio. CFA-treated mice showed delayed avidity maturation. Conclusions: Prior exposure to F. hepatica antigens can modulate the early immune response to Comirnaty^®, affecting both cellular activation and antibody quality. This altered response may reflect a reduced early protective capacity of the vaccine, which might need to be considered when designing or evaluating vaccination strategies using mRNA vaccines in helminth-endemic regions. Full article

Lipid nanoparticles (LNPs) are widely recognized as effective drug delivery systems for RNA therapeutics because their efficacy is critically dependent on structural organization. The mesoscopic architecture of these multicomponent systems, which is governed by interactions among ionizable lipids, structural lipids, nucleic acids, and stabilizers, dictates encapsulation efficiency, biodistribution, and therapeutic performance. Although small-angle X-Ray scattering (SAXS) enables nanostructure characterization, the absence of suitable analytical models has hindered LNP development. Here, we present a core-triple shell SAXS model that resolves LNP hierarchical organization, including the inner lipid layer, intermediate hydrophilic region, and outer PEG corona. For LNPs encapsulating mRNA, a Gaussian distribution model was implemented to characterize the quasi-periodic structure originating from the self-assembly of mRNA-ionizable lipid complexes. Validation studies employing Comirnaty-based LNPs demonstrated that controlled variation of nitrogen-to-phosphorus (N/P) ratios produced distinguishable structural features that establish quantitative correlations between N/P ratios and LNP mesoscopic assembled structure. The modeling framework provides pharmaceutical researchers with robust analytical tools for systematic stability assessment and precision formulation for the optimization of LNPs. These structural insights are expected to advance the development of next-generation RNA therapeutics by potentially enhancing their delivery efficiency and pharmacokinetic properties. Full article

Understanding the long-term dynamics of SARS-CoV-2 neutralizing antibodies is critical for evaluating vaccine-induced protection and informing booster strategies. In this longitudinal study, we analyzed 114 serum samples from 19 individuals across six time points over a three-year period following mRNA vaccination (Comirnaty) and natural SARS-CoV-2 infection. Using pseudotype-based neutralization assays against nine SARS-CoV-2 variants, including major Omicron subvariants (BA.1–BA.5, BQ.1.1, XBB), and anti-S1 IgG ELISA, we observed that antibody levels peaked after the third vaccine dose and remained relatively stable two years later. Neutralization titers rose markedly after the second and third doses, with the highest neutralization observed at two years post-booster. Strong correlations were found between anti-S1 IgG levels and mean neutralization titers for pre-Omicron variants (r = 0.79–0.93; p < 0.05), but only moderate for Omicron subvariants (r ≈ 0.50–0.64). Notably, hybrid immunity (vaccination plus infection) resulted in higher neutralization titers at the final time point compared to vaccine-only participants. The lowest neutralization was observed against XBB, underscoring the immune evasiveness of emerging variants. These findings support the importance of booster vaccination and highlight the added durability of hybrid immunity in long-term protection. Full article

Background/Objectives: Post-market surveillance of COVID-19 vaccines is vital. This study analyzed EudraVigilance data (Jan 2021–Dec 2023) to detect potential safety signals linking COVID-19 vaccines and specific neurological adverse events (aseptic meningitis, Guillain–Barré syndrome, polyradiculoneuropathies, multiple sclerosis, transverse myelitis, neuromyelitis optica). It also explored the impact of non-healthcare professional reports on disproportionality analysis. Methods: EudraVigilance reports were analyzed to quantify neurological events for 5 COVID-19 vaccines and 47 comparators. Disproportionality was assessed using the Proportional Reporting Ratio (PRR). Spearman’s correlation (SCC) was used to examine the impact of non-healthcare professional reports on PRR. Results: An analysis of 4,159,820 COVID-19 vaccine and 114,025 comparator reports showed a reporting decline over time. A higher proportion of adverse drug event reports were submitted by non-healthcare professionals for COVID-19 vaccines compared to control vaccines, a trend observed consistently across 2021 (57.3% vs. 33%, p < 0.001), 2022 (59.4% vs. 36.5%, p = 0.001), and 2023 (42% vs. 24.36%, p = 0.006). In 2023, significant signals (PRR ≥ 2) were found between Jcovden© and polyradiculoneuropathy (PRR 5.4, IC 95% 3.98–7.32), multiple sclerosis (PRR 2.72, IC 95% (1.08–6.87), transverse myelitis (PRR 4.68, IC 95% 1.02–21.35) and neuromyelitis optica (PRR 7.79, IC 95% 3.5–17.37). In addition, both Spikevax© and Comirnaty© showed significant signals with multiple sclerosis (PRR 2.50, IC 95% 1.70–3.68, and PRR 2.33, IC 95% 1.68–3.24) and transverse myelitis (PRR 3.50, IC 95% 1.66–7.50 and PRR 3.58, IC 95% 1.85–6.93). A significant negative correlation between the proportion of reports from non-healthcare professionals and the case/no-case ratio was found (SCC = −0.4683, p = 0.009). Conclusions: While some significant signals emerged in 2023, the combined three-year data showed no vaccine exceeding the PRR threshold of 2. High-quality data and bias mitigation strategies are crucial for accurate PRR estimation in pharmacovigilance and public health. Full article

The COVID-19 pandemic has necessitated urgent measures to curb its spread, with vaccination emerging as a pivotal strategy. This prospective observational study evaluated breakthrough COVID-19 infections among healthcare workers (HCWs) vaccinated with Comirnaty (Pfizer-BioNTech) at a tertiary care hospital in Greece. Over an 8-month period, from February to September 2021, 1958 fully vaccinated HCWs were monitored. Rapid antigen tests and RT-PCR tests were conducted weekly for asymptomatic HCWs. Contact tracing and whole-genome sequencing were performed. Results showed that 2.75% (54 cases) of HCWs experienced breakthrough infections. Among these, 25 (45%) were asymptomatic, mild symptoms occurred in 21 (37%), while 7 (13%) had a fever (≥38 °C) alone and 3 (5%) developed high fever (≥39 °C) with respiratory symptoms. Physicians and nursing staff were the most affected groups. Dominant SARS-CoV-2 variants detected included Delta, British, and Wild type variants. Comparison with existing literature underscored the effectiveness of Comirnaty in reducing breakthrough infections. The findings emphasize the importance of continued booster vaccinations and ongoing surveillance to mitigate breakthrough infections among HCWs. Full article

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on the timing and data analysis methods used. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on the prevalence of AEs and incidents associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of COVID-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer’s pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, with nearly all of them being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with the use of genetic vaccines. The difference is especially pronounced in the case of severe ‘Brighton-listed’ AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases in incidence rates relative to flu vaccines, given as x-fold rises, were 1152x, 455x, 226x, 218x, 162x, 152x, and 131x for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concept that genetic vaccines can be regarded as prophylactic immuno-gene therapies and that the observed chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses which potentially lead to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk/benefit balance of various products. Full article

Introduction: COVID-19, caused by SARS-CoV-2, has disrupted global health systems, with vaccines being essential to mitigating its impact. Statins, widely prescribed for dyslipidemia, are associated with muscle-related side effects, which may worsen during COVID-19. This study explores the association between statin use, COVID-19 vaccination, and skeletal muscle-related symptoms. Aims: To evaluate the association between statin use and muscle symptoms (pain and creatine kinase (CK) levels) in COVID-19 patients and investigate whether vaccination is associated with changes in these symptoms. Methods: This observational study included 147 symptomatic COVID-19 patients: 74 chronic statin users (SG) and 73 non-users (CG). Vaccination status (unvaccinated, one-dose, or two-dose Pfizer–BioNTech) was recorded. Muscle pain was assessed using the Numerical Rating Scale (NRS), and CK levels were measured. Additional factors, including age, sex, BMI, and smoking status, were analyzed. Statistical tests examined the potential associations between statin use, vaccination, and muscle-related outcomes. Results: Higher CK levels were more frequently reported in SG, with severe rhabdomyolysis occurring slightly more often in the SG (4% vs. 3%). Men had higher CK values, while women appeared to be at greater risk of severe rhabdomyolysis. Older adults (≥65 years) in the SG had significantly higher CK levels. Fully vaccinated individuals had lower CK values and reported less muscle pain, while unvaccinated participants had the highest incidence of CK abnormalities and severe muscle pain. No significant differences in CK levels were observed between SARS-CoV-2 variants. Conclusions: Statin use was associated with elevated CK levels and increased muscle pain severity. Older adults and women appeared more susceptible to severe muscle complications. Full vaccination was linked to lower CK values and reduced muscle symptoms. Further research is needed to confirm these findings. Full article

Background/Objectives: In this ongoing, multicenter, global cohort observational study, phenotypes of headaches after COVID-19 vaccination were directly compared between different vaccines. Methods: Phenotypes of postvaccinal headache were recorded in 18,544 participants. The study was launched immediately after the start of the global COVID-19 vaccination campaign on 12 January 2021 and continued until 1 August 2023. Specific aspects of headaches and related variables were collected via an online questionnaire. The clinical headache characteristics of patients vaccinated with the Comirnaty (BioNTech), Jcovden (Johnson & Johnson), Sputnik V (Gamelaya), Covilo (Sinopharm), Spikevax (Moderna), Vaxzevria (AstraZeneca), and Convidecia (CanSino Biologics) vaccines were investigated. Results: Across all vaccines, the median and mean latency of headache onset after vaccine administration were 12 h and 23.3 h, respectively. The median and mean headache duration were 12 h and 23.3 h, respectively. When the nonreplicating viral vector vaccine Sputnik V was used, headaches occurred the fastest, with a latency of 17 h. The latencies for the Vaxzevria and Convidecia nonreplicating viral vector vaccines were 14.9 h and 19.1 h, respectively. The Covilo inactivated whole-virus vaccine had a latency of 20.5 h. The latencies of the mRNA-based Comirnaty and Spikevax vaccines were 26.0 h and 22.02 h, respectively. Analysis of variance revealed no significant differences in the mean duration of postvaccinal headache for the vaccines tested. Compared with the Comirnaty, Covilo, and Vaxzevria vaccines, the Spikevax vaccine induced significantly greater headache intensities. Vaxzevria was associated with a significantly higher frequency of concomitant symptoms than the other vaccines. Conclusions: The phenotype of postvaccinal headache can vary significantly between vaccines. These results have clinical implications for differentiating between postvaccinal headache and other primary and secondary headaches. This knowledge is clinically relevant in differentiating life-threatening vaccination complications, such as thrombotic syndromes, which are also associated with headaches. Based on these results, new diagnostic criteria for postvaccinal headaches can be developed. Full article

In a period globally known as long COVID, several post-acute infection sequelae and vaccination effects have been discussed. Objectives: This study aimed to identify the effects of COVID-19 infection and vaccines on the menstrual cycle of adolescents attending higher education and to verify the association between personal health factors and changes in their menstrual cycle after contact with the virus SARS-CoV-2 via infection or via the vaccine. Methods: A cross-sectional study was conducted using a questionnaire for data collection, applied online to Portuguese higher education adolescents aged between 18 and 24. The sample included 401 individuals. The statistical analysis of data was performed using SPSS. Results: More than half of the sample had a COVID-19 infection only once and took two doses of the vaccine. The mRNA Comirnaty 30 µg BioNTech vaccine was administered to 73.1%. The most common menstrual changes were an increase in blood clots, the blood becoming darker, shorter menstrual cycles, scarcer blood flow, and more irregular cycles. Menstrual changes correlated significantly with vaccination but not with infection. Conclusions: This study showed a lower percentage of women affected than other studies carried out closer to the pandemic period, which could mean that the effects are diminishing over time. Thus, adolescents’ menstrual health should be monitored. Full article

The emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty^® Omicron XBB.1.5-adapted COVID-19 mRNA vaccine, followed by infection with either antigenically closely (EG.5.1) or distantly related (JN.1) Omicron subvariants. Vaccination with the YF17D vector encoding a modified Gamma spike (YF-S0*) served as a control for SARS-CoV-2 immunity restricted to pre-Omicron variants. Our results show that both Comirnaty^® XBB.1.5 and YF-S0* induce robust, however, poorly cross-reactive, neutralizing antibody (nAb) responses. In either case, total antibody and nAb levels increased following infection. Intriguingly, the specificity of these boosted nAbs did not match the respective challenge virus, but was skewed towards the primary antigen used for immunization, suggesting a marked impact of antigenic imprinting, confirmed by antigenic cartography. Furthermore, limited cross-reactivity and rapid decline in nAbs induced by Comirnaty^® XBB.1.5 with EG.5.1 and, more concerning, JN.1, raises doubts about sustained vaccine efficacy against recent circulating Omicron subvariants. In conclusion, we demonstrate that antigenic imprinting plays a dominant role in shaping humoral immunity against emerging SARS-CoV-2 variants. Future vaccine design may have to address two major issues: (i) overcoming original antigenic sin that limits the breadth of a protective response towards emerging variants, and (ii) achieving sustained immunity that lasts for at least one season. Full article

Background: A vaccination programme against severe acute respiratory syndrome coronavirus 2 was initiated in Portugal in December 2020. In this study, we report the findings of a prospective cohort study implemented with the objective of monitoring antibody production in response to COVID-19 vaccination. Methods: The humoral immune response to vaccination was followed up using blood samples collected from 191 healthcare workers. Participants were split into three groups: the Oxford-AstraZeneca (Vaxzevria) vaccine group (n = 68), the Pfizer-BioNTech COVID-19 (Comirnaty) vaccine group (n = 51), and the Post-COVID group (n = 72). The kinetics of anti-spike antibody production were evaluated until 56 days on average after the third dose (booster). Results: We observed that antibody titres peaked approximately one month after full vaccination and declined steadily thereafter. We also found that mRNA vaccination induces higher titres of antibodies than viral vector vaccination, and both generate greater antibody responses than mild or moderate COVID-19. Additionally, whilst the booster for the Oxford-AstraZeneca and Pfizer-BioNTech groups led to antibody levels higher than those at any previous sample collection point, the booster for the Post-COVID group (persons with a history of COVID-19 prior to vaccination) led to antibody levels lower than those attained one month after the second dose. Interpretation: Our results indicate that there are different kinetics of antibody production between individuals who received the Pfizer-BioNtech mRNA vaccine and those who received the Oxford-AstraZeneca vector vaccine, or individuals who had COVID-19 before being vaccinated. Additionally, we observed that exposure to either natural infection or vaccination modulates the response to subsequent vaccination. This is particularly evident after administration of the third dose to the Post-COVID group, where our findings point to a hindrance in vaccine boosting, probably due to unwanted feedback by high titres of pre-existing antibodies. Full article

Background: Conventional vaccines rarely cause severe allergic reactions. However, the rapid development and approval of COVID-19 vaccines left limited initial data on their adverse reactions, particularly in individuals with a history of allergy. The aim of this study was to assess and compare the safety profile of different doses and brands of COVID-19 vaccines in subjects with a history of allergy vs. those without a history of allergy. Methods: From February 2021 to February 2023, a web-based prospective study gathered vaccinee-reported outcomes using electronic questionnaires across eleven European countries. Baseline and up to six follow-up questionnaires captured data on vaccinee demographics, as well as both solicited and unsolicited adverse reactions. Results: Overall, 3476 vaccinees with a history of allergy were matched with 13,872 vaccinees from the general population at the first vaccination cycle and were included in the analysis. A total of 825 vaccinees with a history of allergy who had received a booster dose, matched to 3297 vaccinees from the general population, were included in the analysis. Higher rates of ADRs occurred after the first vaccination cycle compared to after the booster dose (64–91% vs. 56–79%). However, most reported ADRs were solicited and not serious, and no case of anaphylaxis was reported. Women and vaccinees with a history of allergy reported ADRs more frequently than men and the matched controls, respectively. Compared to other COVID-19 vaccines, a higher proportion of vaccinees experiencing at least one ADR following their first vaccination cycle was observed with Comirnaty and Vaxzevria. Statistically significant differences were observed among the study cohorts for median TTO after the second dose, and for median TTR following the first vaccination cycle and booster dose (p < 0.001). Conclusions: Typically, any drug or vaccine use carries a risk of severe allergic reactions, yet the benefits of vaccination generally outweigh these potential risks, as shown with the COVID-19 vaccines. Full article

This study aimed to assess the real-world effectiveness of vaccines and hybrid immunity in preventing infections during the Omicron prevalent period in Hong Kong. This study analyzed vaccination records and COVID-19 confirmed case records from 1 January 2022 to 28 January 2023 and included a total of 7,165,862 individuals with vaccination or infection records. This study found that an additional vaccine dose offered increased protection against Omicron BA.1/2 and BA.4 infections for individuals without prior infections in general. Hybrid immunity, acquired through vaccination and natural infection, was found to be significantly stronger than that provided by vaccines alone. The Comirnaty Original/Omicron BA.4/5 bivalent vaccine, introduced in December 2022, was associated with a lower risk of BA.4 infection when administered as a booster dose after three doses of CoronaVac. However, individuals with four doses of the CoronaVac vaccine did not exhibit a significantly lower risk of infection compared to those with three doses during the BA.4 dominant period. This study highlights the importance of promoting booster shot uptake and encouraging vaccination among those who have recovered from COVID-19 infections. The potential immune imprinting effect associated with the Comirnaty and CoronaVac vaccine underscores the need for continued surveillance and research to optimize vaccination strategies for emerging variants. Full article

In December 2020, a major vaccination program against COVID-19 commenced in Europe with vaccines such as Pfizer’s mRNABNT162b2 (Comirnaty^®). Subsequent reports of immediate and delayed skin reactions emerged. This study presents a case of a 64-year-old male who developed multiple keratoacanthomas approximately two weeks after receiving a second booster dose of the Pfizer vaccine. The patient, who had significant medical history of hypertension and diabetes, presented with erythematous, crateriform lesions on his limbs. A physical examination and histopathological analysis confirmed the diagnosis of Generalized Eruptive Keratoacanthoma (GEKA). Treatment involved cemiplimab I.v. 350 mg administered every three weeks. Within two months, the patient showed significant improvement, with the disappearance of all lesions. Dermoscopy and histopathological exams supported the GEKA diagnosis, which is a rare variant of multiple keratoacanthomas. This case suggests a potential immune-mediated mechanism triggered by the COVID-19 vaccine, leading to the rapid development of keratoacanthomas. Treatment with cemiplimab showed promise, highlighting the potential of immune checkpoint inhibitors in managing multiple keratoacanthomas. Further research is needed to explore the efficacy and safety of such treatments. Full article