Full-length nanopore sequencing of circular RNA landscape in peripheral blood cells following sequential BNT162b2 mRNA vaccination.

Circular RNAs (circRNA) lack 5' or 3' ends; their unique covalently closed structures prevent RNA degradation by exonucleases. These characteristics provide circRNAs with high pharmaceutical stability and biostability relative to current standard-of-care linear mRNAs. CircRNA levels are reportedly associated with certain human diseases, making them novel disease biomarkers and a noncanonical class of therapeutic targets. In this study, the endogenous circRNAs underlying the response to BNT162b2 mRNA vaccination were evaluated. To this end, peripheral blood samples were subjected to full-length sequencing of circRNAs via nanopore sequencing and transcriptome sequencing. Fifteen samples, comprising pre-, first, and second vaccination cohorts, were obtained from five healthcare workers with no history of SARS-CoV-2 infection or previous vaccination. A total of 4706 circRNAs were detected; following full-length sequencing, 4217 novel circRNAs were identified as being specifically expressed during vaccination. These circRNAs were enriched in the binding motifs of stress granule assemblies and SARS-CoV-2 RNA binding proteins, namely poly(A) binding protein cytoplasmic 1 (PABPC1), pumilio RNA binding family member 1 (PUM1), and Y box binding protein 1 (YBX1). Moreover, 489 circRNAs were identified as previously reported miRNA sponges. The differentially expressed circRNAs putatively originated from plasma B cells compared to circRNAs reported in human blood single-cell RNA sequencing datasets. The pre- and post-vaccination differences observed in the circRNA expression landscape in response to the SARS-CoV-2 BNT162b2 mRNA vaccine.

Comparative study of neutralizing antibodies titers in response to different types of COVID-19 vaccines among a group of egyptian healthcare workers.

BACKGROUND: Defining the protective thresholds against the severe-acute-respiratory-syndrome-related corona virus-2 pandemic is a crucial challenge. To reduce the risks of severe disease, hospitalization, and death, various COVID-19 vaccines have been rapidly developed. AIM OF THE WORK: This study aimed to assess the impact of three common COVID-19 vaccine types; two mRNA COVID-19 vaccines: (Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273), one adenoviral vector vaccine: Oxford/AstraZeneca's ChAdOx1, and one inactivated vaccine (Sinovac Biotech/China's Sinovac) on the level of neutralizing antibodies, considering factors such as vaccine type, demographic characteristics, and hybrid immunity. We conducted a direct comparative analysis involving 300 healthcare workers, both with and without prior SARS-CoV-2 infection (B.1, C.36.3, and AY.32 (Delta) variants). Neutralizing antibodies levels were measured at baseline (before vaccination), before the second dose, and six months after the second dose. RESULTS: The results showed a significant increase in neutralizing antibodies levels after complete vaccination with all vaccine types. Among healthcare workers, those vaccinated with mRNA vaccines (Moderna or Pfizer) exhibited the highest neutralizing antibodies titers, followed by AstraZeneca, and finally Sinovac with the lowest titer. On studying the effect of previous COVID-19 infection after vaccination, no significant difference in neutralizing antibodies levels was observed between healthcare workers vaccinated with mRNA or AstraZeneca vaccines, both with prior COVID-19 infection, following the first and six months after the second dose. CONCLUSION: These findings suggest that individuals with prior COVID-19 may only require a single dose of mRNA or AstraZeneca vaccines to achieve a similar level of immunization as those without prior COVID-19 who completed the vaccination program. HIGHLIGHTS: There is a significant increase in neutralizing antibodies levels after complete vaccination against COVID-19 Vaccination with mRNA vaccines exhibits the highest neutralizing antibodies titers. Vaccination with Sinovac exhibits the lowest neutralizing antibodies titers.

Comparable and sustained levels of S1-RBD-IgG and S1-RBD-IgA in BNT162b2 homologous and CoronaVac-BNT162b2 heterologous booster vaccination: A 22-month prospective study in Malaysia.

This prospective cohort study examines the long-term humoral immune responses post-COVID-19 vaccination in 146 individuals who received either a homologous three-dose BNT162b2 vaccine regimen (PPP) or two primary doses of CoronaVac followed by BNT162b2 booster (SSP) in Malaysia. The study focuses on serum anti-S1-RBD-IgG, -IgA, and -IgM, using the ELISA method. The results show that BNT162b2 outperformed CoronaVac in the two dose primary vaccination series. BNT162b2 booster dose significantly raised serum anti-S1-RBD-IgG and -IgA levels, sustaining this increase from 26 to 52 weeks after administration, regardless of the vaccine regimen. This leads to equivalent levels of anti-S1-RBD-IgG and -IgA after boosting with BNT162b2 in both groups. Breakthrough infections, particularly with the emergence of the Omicron variant, did not result in increased anti-S1-RBD-IgG and -IgA levels. No significant induction of anti-S1-RBD-IgM was observed following multiple vaccine doses. The long-term investigation revealed that PPP and SSP groups had comparable humoral immune responses to SARS-CoV-2, highlighting the advantage of mRNA booster dose in our cohort.

Associations between symptom-based long COVID clusters and long-term quality of life, work and daily activities among individuals testing positive for SARS-CoV-2 at a national retail pharmacy.

BACKGROUND: Evidence on long COVID symptom clustering patterns among patients with COVID-19 is limited. We summarized long COVID symptoms in clusters defined by number of symptoms co-occurring together, and we assessed Health-Related Quality of Life (HQRoL), Work Productivity and Activity Impairment (WPAI) outcomes across these clusters over time. We assessed associations between the clusters and BNT162b2 vaccination status. METHODS: A prospective longitudinal patient-reported outcomes (PRO) study recruited laboratory-confirmed symptomatic COVID-19 patients seeking testing from a national retail pharmacy. Long COVID-19 symptoms were self-reported by participants at 4-week, 3-month and 6-month surveys. Patient classes identified via latent class analysis (LCA) with long COVID-19 symptoms were simplified into clusters based on number of symptoms. HRQoL and WPAI outcomes were collected using EQ-ED-5L and WPAI: GH questionnaires. Mixed models for repeated measures analyses were conducted to examine associations between exposure groups and outcomes. RESULTS: The study included 328 participants that were segmented into three groups of long COVID-19 symptoms based on LCA and then simplified by the number of symptoms (Cluster 1 low, <2; Cluster 2 moderate, 2-6; and Cluster 3 high, >6 symptoms). The number of long COVID-19 symptoms was negatively associated with HRQoL and WPAI, whereby participants with high symptom burden (>6 symptoms) had the lowest HRQoL and WPAI scores assessed by absenteeism, presenteeism, work productivity loss, activity impairment, and hours worked metrics. Compared with those unvaccinated and not up-to-date with COVID-19 vaccination, subjects boosted with BNT162b2 consistently reported less symptom burden during the follow-up, regardless of their symptom-based cluster. CONCLUSION: Three distinct patient clusters based on frequency of long COVID symptoms experienced different HRQoL and WPAI outcomes over 6 months. The cluster with more concomitant symptoms experienced greater burden than the others. Participants up-to-date with BNT162b2 reported lower symptom burden across all clusters and timeframes. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT05160636.

Comparative Effectiveness of the Bivalent (Original/Omicron BA.4/BA.5) mRNA COVID-19 Vaccines mRNA-1273.222 and BNT162b2 Bivalent in Adults with Underlying Medical Conditions in the United States.

BACKGROUND/OBJECTIVES: This retrospective cohort study evaluated the relative vaccine effectiveness (rVE) of two bivalent (original/Omicron BA.4/BA.5) vaccines mRNA-1273.222 versus the BNT162b2 Bivalent in preventing COVID-19-related outcomes in adults with underlying medical conditions associated with increased risk for severe COVID-19. METHODS: In a linked electronic health record/claims dataset, US adults (≥18 years) with ≥1 underlying medical condition of interest who received either the bivalent vaccine between 31 August 2022 and 28 February 2023 were identified. The inverse probability of treatment weighting was used to adjust for cohort differences. Cohorts were followed up for COVID-19-related hospitalizations and outpatient encounters until 31 May 2023. Hazard ratios and rVEs were estimated using Cox regression. Subgroup analyses were performed on individuals with pre-specified comorbid conditions. RESULTS: 757,572 mRNA-1273.222 and 1,204,975 BNT162b2 Bivalent recipients were identified. The adjusted rVE over a median follow-up of 198 days was 10.9% (6.2%-15.2%) against COVID-19-related hospitalization and 3.2% (1.7%-4.7%) against COVID-19-related outpatient encounters. rVE estimates for COVID-19 hospitalizations among subgroups with comorbid conditions were as follows: diabetes 15.1% (8.7%-21.0%), cerebro- and cardiovascular disease 14.7% (9.0%-20.1%), chronic lung disease 11.9% (5.1%-18.2%), immunocompromised 15.0% (7.2%-22.2%), chronic kidney disease 8.4% (0.5%-15.7%). CONCLUSIONS: Overall, among adults with underlying medical conditions, mRNA-1273.222 was more effective than BNT162b2 Bivalent, especially in preventing COVID-19-related hospitalizations.

Modelling the Relative Vaccine Efficacy of ARCT-154, a Self-Amplifying mRNA COVID-19 Vaccine, versus BNT162b2 Using Immunogenicity Data.

Background: Self-amplifying mRNA vaccines have the potential to increase the magnitude and duration of protection against COVID-19 by boosting neutralizing antibody titers and cellular responses. Methods: In this study, we used the immunogenicity data from a phase 3 randomized trial comparing the immunogenicity of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, with BNT162b2 mRNA COVID-19 vaccine to estimate the relative vaccine efficacy (rVE) of the two vaccines over time in younger (<60 years) and older (≥60 years) adults. Results: By day 181 post-vaccination, the rVE against symptomatic and severe Wuhan-Hu-1 disease was 9.2-11.0% and 1.2-1.5%, respectively, across age groups whereas the rVE against symptomatic and severe Omicron BA.4/5 disease was 26.8-48.0% and 5.2-9.3%, respectively, across age groups. Sensitivity analysis showed that varying the threshold titer for 50% protection against severe disease up to 10% of convalescent sera revealed incremental benefits of ARCT-154 over BNT162b2, with an rVE of up to 28.0% against Omicron BA.4/5 in adults aged ≥60 year. Conclusions: Overall, the results of this study indicate that ARCT-154 elicits broader and more durable immunogenicity against SARS-CoV-2, translating to enhanced disease protection, particularly for older adults against Omicron BA.4/5.

Blood transcriptome profiling reveals distinct gene networks induced by mRNA vaccination against COVID-19.

Messenger RNA (mRNA) vaccines represent a new class of vaccines that has been shown to be highly effective during the COVID-19 pandemic and that holds great potential for other preventative and therapeutic applications. While it is known that the transcriptional activity of various genes is altered following mRNA vaccination, identifying and studying gene networks could reveal important scientific insights that might inform future vaccine designs. In this study, we conducted an in-depth weighted gene correlation network analysis of the blood transcriptome before and 24 h after the second and third vaccination with licensed mRNA vaccines against COVID-19 in humans, following a prime vaccination with either mRNA or ChAdOx1 vaccines. Utilizing this unsupervised gene network analysis approach, we identified distinct modular networks of co-varying genes characterized by either an expressional up- or downregulation in response to vaccination. Downregulated networks were associated with cell metabolic processes and regulation of transcription factors, while upregulated networks were associated with myeloid differentiation, antigen presentation, and antiviral, interferon-driven pathways. Within this interferon-associated network, we identified highly connected hub genes such as STAT2 and RIGI and associated upstream transcription factors, potentially playing important regulatory roles in the vaccine-induced immune response. The expression profile of this network significantly correlated with S1-specific IgG levels at the follow-up visit in vaccinated individuals. Those findings could be corroborated in a second, independent cohort of mRNA vaccine recipients. Collectively, results from this modular gene network analysis enhance the understanding of mRNA vaccines from a systems immunology perspective. Influencing specific gene networks could lead to optimized vaccines that elicit augmented vaccine responses.

Predicting herd immunity achievement: a time-series analysis of vaccination and fatality rates using 1,075 days of COVID-19 data.

Introduction: The COVID-19 pandemic, driven by SARS-CoV-2, has made vaccination a critical strategy for global control. However, vaccine hesitancy, particularly among certain age groups, remains a significant barrier to achieving herd immunity. Methods: This study uses Poisson regression and ARIMA time-series modeling to identify factors contributing to vaccine hesitancy, understand age-specific vaccination preferences, and assess the impact of bivalent vaccines on reducing hesitancy and fatality rates. It also predicts the time required to achieve herd immunity by analyzing factors such as vaccine dosing intervals, age-specific preferences, and changes in fatality rates. Results: The study finds that individuals recovering from COVID-19 often delay vaccination due to perceived immunity. There is a preference for combining BNT162b2 and CoronaVac vaccines. The BNT162b2 bivalent vaccine has significantly reduced vaccine hesitancy and is linked with lower fatality rates, particularly in those aged 80 and above. However, it tends to induce more severe side effects compared to Sinovac. Vaccine hesitancy is most prevalent among the youngest (0-11) and oldest (80+) age groups, posing a challenge to reaching 90% vaccination coverage. Conclusion: Vaccine hesitancy is a major obstacle to herd immunity. Effective strategies include creating urgency, offering incentives, and prioritizing vulnerable age groups. Despite these challenges, the government should have continued to encourage vaccinations while gradually lifting COVID-19 control measures, balancing public health safety with the return to normal life, as was observed in the transition period during the latter stages of the pandemic.

Public Health and Economic Impact of Periodic COVID-19 Vaccination with BNT162b2 for Old Adults and High-Risk Patients in an Illustrative Prefecture of Japan: A Budget Impact Analysis.

INTRODUCTION: Japan will be transitioning from the free-of-charge COVID-19 vaccination program to annual periodic vaccination under a national immunization program for old adults and high-risk patients from 2024 fall/winter season. The policy transition including out-of-pocket payment requirement may discourage vaccination, leading to a lower vaccination rate. This study aimed to estimate the impact of varying vaccination rates with BNT162b2 COVID-19 mRNA vaccine on economics and public health in an illustrative prefecture which administers and promotes the periodic vaccination program, using budget impact analysis. METHODS: A combined cohort Markov decision tree model estimated the public health outcomes of COVID-19-related symptomatic cases, hospitalizations and deaths; and the economic outcomes including vaccine-related cost, non-vaccine-related medical cost, and productivity loss from the societal perspective. The base case examined the impact on the outcomes when vaccination coverage changed from the reference value of 50% to upper and lower values, respectively. Scenario analyses were performed based on multiple scenarios. RESULTS: Increase in the vaccination rate demonstrated improvement in all public health outcomes. At 50% vaccination, the vaccine-related cost for 3 years in a prefecture was estimated at JPY 7.58 billion (USD 57.67 million), the non-vaccine-related medical cost at JPY 79.22 billion (USD 602.48 million), the productivity loss at JPY 253.11 billion (USD 1.92 billion), and the total cost at JPY 339.92 billion (USD 2.59 billion). When the vaccination rate increased to 90%, the total cost decreased by JPY 4.88 billion (USD 37.11 million) (1.4%). When the vaccination rate decreased to 10%, the total cost increased by JPY 5.73 billion (USD 43.58 million) (1.7%). Results were consistent across almost all scenario analyses. CONCLUSIONS: Maintaining a high vaccination rate with BNT162b2 is important from both public health and economic perspectives in Japan. The findings highlight to local governments the importance of continued effort to promote vaccination.

The descriptive epidemiology of adverse events following two doses of mRNA COVID-19 vaccination in Curaçao, the Caribbean.

BACKGROUND: BNT162b2 and mRNA-1273 COVID-19 vaccines have been used for mass vaccinations in Curaçao, the Caribbean but information on adverse events (AEs)in this population is unavailable. This study describes the characteristics of vaccinees that incurred AEs, explores the associations between AEs by vaccine and doses, and estimates the rate of AEs. METHODS: Vaccination and AEs data for all persons of age 5 years (range 5-105 years) and older who received two doses of COVID-19 vaccine at 71 centres in Curaçao between February 24, 2021, and April 5, 2023, were included in this retrospective observational study. RESULTS: The vaccines differed significantly in the frequency distribution of vaccinees by age, age groups, sex, AEs, and prior COVID-19 infection. Occurrence of AEs was strongly associated with mRNA vaccine brand, sex, number of doses, but not with age, age group, and prior COVID-19 infection. Of 209,720 doses, 84 persons (0.04%) incurred AEs following two doses of mRNA vaccines (overall rate of 40.1 per 100,000 persons (95% CI 32.4-49.6). AEs were also significantly higher in females compared to males.AE rates associated with BNT162b2, and mRNA-1273 vaccines were low, but BNT162b2 vaccinees incurred substantially significantly higher AE rates (58.3 per 100,000 persons, 95% CI 45.4-74.9) than mRNA-1273 vaccinees (21.9 per 100,000 persons, 95% CI 14.6-32.8). mRNA-1273 vaccine was associated with a significantly lower risk of AEs. CONCLUSIONS: AE reporting varied by age, sex, and vaccine used as well as the number of doses. Future studies with follow-up and longer-term reporting of AEs should be conducted.

Vaccine-induced humoral response of BNT162b2 and mRNA-1273 against BA.1, BA.5, and XBB.1.5. (sub)variants 6 months after a homologous booster: is immunogenicity equivalent?

Introduction: Some studies suggest that the monovalent mRNA-1273 vaccine is more effective than BNT162b2 in producing higher levels of antibodies. However, limited data are available, and the methods used are not directly comparable. Material and methods: Blood samples were obtained before the booster (third dose) and after 14, 90, and 180 days in two similar cohorts who received the original BNT162b2 or mRNA-1273 vaccine designed to target wild type SARS-CoV-2. The aim of our study is to compare their effectiveness by assessing the levels of binding and neutralizing antibodies specifically against each of the BA.1 variant, BA.5 variant, and the XBB.1.5 subvariant. Results: Once the peak was reached after two weeks, a drastic decline in binding and neutralizing antibodies was observed up to 6 months after the homologous booster administration. The humoral response was however more sustained with the mRNA-1273 booster, with half-lives of 167, 55, and 48 days for binding, BA.1, and BA.5 neutralizing antibodies compared to 144, 30, and 29 days for the BNT162b2 booster, respectively. Compared to the BA.1 variant, the neutralizing capacity was significantly decreased at 6 months with the BA.5 variant (fold-decrease: 1.67 to 3.20) and the XBB.1.5. subvariant (fold-decrease: 2.86 to 5.48). Conclusion: Although the decrease in the humoral response was observed with both mRNA vaccines over time, a more sustained response was observed with the mRNA-1273 vaccine. Moreover, the emergence of Omicron-based variants causes a reduced neutralizing capacity, notably with the XBB.1.5. subvariant. The administration of subsequent boosters would therefore be needed to restore a sufficiently high neutralizing response.

Durability for 12 months of antibody response to a booster dose of monovalent BNT162b2 in adults who had initially received 2 doses of inactivated vaccine.

This study examined the strength and durability of antibody responses in 277 adults who received a heterologous third dose of the BNT162b2 vaccine, following two doses of an inactivated vaccine. Neutralizing antibody levels against both the ancestral virus and Omicron BA.2 subvariant decreased from one month to 6 months after the third dose, and were then maintained at 12 months. Participants who received both a fourth dose and reported a SARS-CoV-2 infection had the highest antibody titers at 365 days after the third dose. Individuals with chronic medical conditions had lower antibody levels against the Omicron BA.2 subvariant at 12 months after the third dose. The results suggest that the heterologous third dose provides durable neutralizing antibody responses, which may be influenced by subsequent infection or vaccination and pre-existing medical conditions. These findings may help explain the differences in immune protection between vaccination and natural infection.

Endurance Exercise Does Not Exacerbate Cardiac Inflammation in BALB/c Mice Following mRNA COVID-19 Vaccination.

The mechanism underlying myopericarditis associated with mRNA COVID-19 vaccination, including increased susceptibility in young males, remains poorly understood. This study aims to explore the hypothesis that engaging in physical exercise at the time of mRNA COVID-19 vaccination may promote a cardiac inflammatory response, leading to the development of myopericarditis. Male BALB/c mice underwent treadmill running or remained sedentary for five weeks. Subsequently, two doses of the Pfizer/BioNTech vaccine or vehicle were administered with a 14-day interval, while the exercise regimen continued. The animals were euthanized days after the second vaccination. Vaccination was followed by body weight loss, increased hepatic inflammation, and an antigen-specific T cell response. Small foci of fibrovascular inflammation and focal cell loss were observed in the right ventricle, irrespective of vaccination and/or exercise. Vaccination did not elevate cardiac troponin levels. Cardiac tissue from the vaccinated mice showed upregulated mRNA expression of the genes IFNγ and IL-1ß, but not IL-6 or TNFα. This pro-inflammatory signature in the heart was not exacerbated by endurance exercise. Ex vivo vascular reactivity remained unaffected by vaccination. Our data provide evidence for the cardiac safety of mRNA COVID-19 vaccination. The role of exercise in the development of pro-inflammatory cardiac changes post mRNA vaccination could not be established.

Sex differences in symptoms following the administration of BNT162b2 mRNA COVID-19 vaccine in children below 5 years of age in Germany (CoVacU5): a retrospective cohort study.

BACKGROUND: Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. METHODS: This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. RESULTS: The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5-10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. CONCLUSIONS: Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759).

For many childhood vaccines, the immune responses are different between the sexes. For the COVID-19 vaccine BNT162b2, the symptoms occurring after vaccination in children have not sufficiently been investigated. In this study, we performed an analysis of a dataset of retrospectively collected information on symptoms occurring after vaccinations with BNT162b2 and regular childhood vaccines in 7801 children under the age of 5 years in Germany, with a focus on the sex differences. Among the four categories assessed, local injection-site and general symptoms were more frequent in girls compared to boys. In contrast, following the administration of other childhood vaccines, the caregivers more frequently reported muscle-related symptoms in boys than in girls. In conclusion, sex differences exist in symptoms occurring after vaccinations even in young children, which is important to consider for future studies evaluating vaccine safety.

SARS-CoV-2 spike protein antibody titers after the fourth dose of BNT162b2 vaccine among Japanese patients undergoing hemodialysis: a single-center study.

Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine.

A Brighton Collaboration standardized template with key considerations for a benefit-risk assessment for the Comirnaty COVID-19 mRNA vaccine.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4-5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.

Comparison of Adverse Events and Antibody Responses Among Different COVID-19 Vaccination Schedules.

Global investment in developing COVID-19 vaccines has been substantial, but vaccine hesitancy has emerged due to misinformation. Concerns about adverse events, vaccine shortages, dosing confusion, mixing vaccines, and access issues contribute to hesitancy. Initially, the WHO recommended homologous vaccination (same vaccine for both doses), but evolving factors led to consideration of heterologous vaccination (different vaccines). The study compared reactogenicity and antibody response for both viral protein spike (S) and nucleocapsid (N) in 205 participants who received three vaccination regimens: same vaccine for all doses (Pfizer), two initial doses of the same vaccine (CoronaVac or AstraZeneca), and a Pfizer booster. ChAdOx1 and BNT162b2 vaccines were the most reactogenic vaccines, while CoronaVac vaccine was the least. ChAdOx1 and BNT162b2 achieved 100% of S-IgG seropositivity with one dose, while CoronaVac required two doses, emphasizing the importance of the second dose in achieving complete immunization across the population with different vaccine regimes. Pfizer recipients showed the highest S-IgG antibody titers, followed by AstraZeneca recipients, both after the first and second doses. A third vaccine dose was essential to boost the S-IgG antibodies and equalize the antibody levels among the different vaccine schedules. CoronaVac induced N-IgG antibodies, while in the Pfizer and AstraZeneca groups, they were induced by a natural infection, reinforcing the role of N protein as a biomarker of infection.

Reports of Batch-Dependent Suspected Adverse Events of the BNT162b2 mRNA COVID-19 Vaccine: Comparison of Results from Denmark and Sweden.

Background and Objective: An unexpected batch-dependent safety signal for the BNT162b2 mRNA COVID-19 vaccine was recently identified in a nationwide study from Denmark, but the generalizability of this finding is unknown. Therefore, we compared batch-dependent rates of suspected adverse events (SAEs) reported to national authorities in Denmark and Sweden. Materials and Methods: SAE and vaccine batch data were received from national authorities in Denmark and Sweden, and analyses of heterogeneity in the relationship between numbers of vaccine doses and SAEs per batch were performed, along with comparison of SAE rates and severities for batches that were shared between the two countries. Results: Significant batch-dependent heterogeneity was found in the number of SAEs per 1000 doses for both countries, with batches associated with high SAE rates detected in the early phase of the vaccination campaign and positive correlations observed between the two countries for the severity of SAEs from vaccine batches that they shared. Mild SAEs predominated in the batches used in the early part of the vaccination roll-out, where markedly higher SAE rates per 1000 doses in Denmark for the batches that were shared between the two countries suggested that a large proportion of these SAEs were under-reported in Sweden. Conclusions: The batch-dependent safety signal observed in Denmark and now confirmed in Sweden suggests that early commercial batches of BNT162b2 may have differed from those used later on, and these preliminary and hypothesis-generating results warrant further study.

SARS-CoV-2 mRNA vaccine-related myocarditis and pericarditis: An analysis of the Japanese Adverse Drug Event Report database.

BACKGROUND: The association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines and myocarditis/pericarditis in the Japanese population has not been systematically investigated. This study was aimed at clarifying the association between SARS-CoV-2 mRNA vaccines (BNT162b2 and mRNA-1273) and myocarditis/pericarditis as well as influencing factors by using the Japanese Adverse Drug Event Report database. METHODS: Reporting odds ratios (RORs) and 95 % confidence intervals (95 % CIs) for the association between the vaccines and myocarditis/pericarditis were calculated using data from the database (April 2004-December 2023). Age, sex, onset time, and outcomes in symptomatic patients were evaluated. RESULTS: The total number of reports was 880,999 (myocarditis: 1846; pericarditis: 761). The adverse events associated with the vaccines included myocarditis (919 cases) and pericarditis (321 cases), with the ROR [95 % CIs] being significant for both (myocarditis: 30.51 [27.82-33.45], pericarditis: 21.99 [19.03-25.40]). Furthermore, the ROR [95 % CIs] of BNT162b2 and mRNA-1273 were 15.64 [14.15-17.28] and 54.23 [48.13-61.10], respectively, for myocarditis, and 15.78 [13.52-18.42] and 27.03 [21.58-33.87], respectively, for pericarditis. Furthermore, most cases were ≤30 years or male. The period from vaccination to onset was ≤8 days, corresponding to early failure type based on analysis using the Weibull distribution. Outcomes were recovery or remission for most cases; however, they were severe or caused death in some cases. CONCLUSION: In the Japanese population, SARS-CoV-2 mRNA vaccination was significantly associated with the onset of myocarditis/pericarditis. The influencing factors included age of ≤30 years and male. Furthermore, although most adverse events occurred early after vaccination, overall outcomes were good.