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.

Novel Less Toxic, Lymphoid Tissue-Targeted Lipid Nanoparticles Containing a Vitamin B5-Derived Ionizable Lipid for mRNA Vaccine Delivery.

Following their approval by the Food and Drug Administration, lipid nanoparticles (LNPs) have emerged as promising tools for delivering mRNA vaccines and therapeutics. Ionizable lipids are among the essential components of LNPs, as they play crucial roles in encapsulating mRNA and facilitating its release into the cytosol. In this study, 17 innovative ionizable lipids using vitamin B5 are designed as the core structure, aiming to reduce toxicity, to maintain vaccine efficiency, and to ensure synthetic feasibility. The top-performing LNP in terms of mRNA vaccine delivery in the mouse model is LNP 5097, which is generated by incorporating ionizable lipid I97. mRNA⊂LNP 5097 demonstrates favorable structural and physicochemical properties, high mRNA transfection efficiency, and long-term stability. Moreover, mRNA⊂LNP 5097 specifically delivers the mRNA to the spleen and lymph nodes in model mice, induces balanced Th1/Th2 immune responses, and elicits the production of high levels of neutralizing antibodies with low toxicity. The findings here suggest the high utility of LNP 5097, which includes novel vitamin B5-derived ionizable lipids with reduced toxicity, in mRNA vaccine research for both infectious diseases and cancer.

Cytokine Storms and Anaphylaxis Following COVID-19 mRNA-LNP Vaccination: Mechanisms and Therapeutic Approaches.

Acute adverse reactions to COVID-19 mRNA vaccines are a major concern, as autopsy reports indicate that deaths most commonly occur on the same day of or one day following vaccination. These acute reactions may be due to cytokine storms triggered by lipid nanoparticles (LNPs) and anaphylaxis induced by polyethene glycol (PEG), both of which are vital constituents of the mRNA-LNP vaccines. Kounis syndrome, in which anaphylaxis triggers acute coronary syndrome (ACS), may also be responsible for these cardiovascular events. Furthermore, COVID-19 mRNA-LNP vaccines encompass adjuvants, such as LNPs, which trigger inflammatory cytokines, including interleukin (IL)-1ß and IL-6. These vaccines also produce spike proteins which facilitate the release of inflammatory cytokines. Apart from this, histamine released from mast cells during allergic reactions plays a critical role in IL-6 secretion, which intensifies inflammatory responses. In light of these events, early reduction of IL-1ß and IL-6 is imperative for managing post-vaccine cytokine storms, ACS, and myocarditis. Corticosteroids can restrict inflammatory cytokines and mitigate allergic responses, while colchicine, known for its IL-1ß-reducing capabilities, could also prove effective. The anti-IL-6 antibody tocilizumab also displays promising treatment of cytokine release syndrome. Aside from its significance for treating anaphylaxis, epinephrine can induce coronary artery spasms and myocardial ischemia in Kounis syndrome, making accurate diagnosis essential. The upcoming self-amplifying COVID-19 mRNA-LNP vaccines also contain LNPs. Given that these vaccines can cause a cytokine storm and allergic reactions post vaccination, it is crucial to consider corticosteroids and measure IL-6 levels for effective management.

AntigenBoost: enhanced mRNA-based antigen expression through rational amino acid substitution.

Messenger RNA (mRNA) vaccines represent a groundbreaking advancement in immunology and public health, particularly highlighted by their role in combating the COVID-19 pandemic. Optimizing mRNA-based antigen expression is a crucial focus in this emerging industry. We have developed a bioinformatics tool named AntigenBoost to address the challenge posed by destabilizing dipeptides that hinder ribosomal translation. AntigenBoost identifies these dipeptides within specific antigens and provides a range of potential amino acid substitution strategies using a two-dimensional scoring system. Through a combination of bioinformatics analysis and experimental validation, we significantly enhanced the in vitro expression of mRNA-derived Respiratory Syncytial Virus fusion glycoprotein and Influenza A Hemagglutinin antigen. Notably, a single amino acid substitution improved the immune response in mice, underscoring the effectiveness of AntigenBoost in mRNA vaccine design.

Poly(ß-amino ester) polymer library with monomer variation for mRNA delivery.

Non-viral vectors for mRNA delivery primarily include lipid nanoparticles (LNPs) and polymers. While LNPs are known for their high mRNA delivery efficiency, they can induce excessive immune responses and cause off-target effects, potentially leading to side effects. In this study, we aimed to explore polymer-based mRNA delivery systems as a viable alternative to LNPs, focusing on their mRNA delivery efficiency and potential application in mRNA vaccines. We created a library of poly(ß-amino ester) (PBAE) polymers by combining various amine monomers and acrylate monomers. Through screening this polymer library, we identified specific polymer nanoparticles (PNPs) that demonstrated high mRNA expression efficiency, with sustained mRNA expression for up to two weeks. Furthermore, the PNPs showed mRNA expression only at the injection site and did not exhibit liver toxicity. Additionally, when assessing immune activation, the PNPs significantly induced T-cell immune activation and were effective in the plaque reduction neutralization test. These results suggest that polymer-based mRNA delivery systems not only hold potential for use in mRNA vaccines but also show promise for therapeutic applications.

Safety and immunogenicity of a SARS-CoV-2 mRNA vaccine (SYS6006) in minks, cats, blue foxes, and raccoon dogs.

Minks, cats, and some other species of carnivores are susceptible of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have a high risk of transmitting SARS-CoV-2 to humans. The development of animal vaccines can be an effective measure to protect animals against SARS-CoV-2 and reduce the potential risk of human infection. We previously developed a messenger ribonucleic acid (mRNA) vaccine SYS6006 that has been proven to be an efficient coronavirus disease 2019 (COVID-19) vaccine widely used in humans. Here, we further evaluated the safety and immunogenicity of SYS6006 as an animal COVID-19 vaccine candidate for SARS-CoV-2 susceptible animals or wild animals. SYS6006 was safe and immunogenic in mice and completely protected mice against mouse-adapted SARS-CoV-2 infection in the upper and lower respiratory tracts. SYS6006 was able to induce neutralizing antibodies against the SARS-CoV-2 wild-type, Delta, and Omicron BA.2 strain on day 7 after prime immunization, and two doses of immunization could enhance the neutralizing antibody responses and produce long-lasting potent antibodies for more than 8 months in minks and cats, blue foxes, and raccoon dogs, while all immunized animals had no abnormal clinical signs during immunization. These results provided here warrant further development of this safe and efficacious mRNA vaccine platform against animal COVID-19.

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.

The Recent Research Progress of the Tumor mRNA Vaccine.

Tumors have long posed a significant threat to human life and health, and the messenger ribonucleic acid (mRNA) vaccine is seen as an attractive approach for cancer immunotherapy due to its developmental simplicity, rapid manufacture, and increased immune safety and efficiency. In this review, we have summarized details of the developmental history of mRNA vaccines, discussed the basic molecular structure and the effect on the stable and translation level of mRNA, analyzed the underlying immune efficiency and mechanisms on tumors, and assessed the current status of clinical research. We explored the treatment and application prospects of mRNA vaccines, aiming to provide perspectives on the future of mRNA tumor vaccines for ongoing clinical research.

Breakthroughs in synthetic controlling strategies for precision in CAR-T therapy.

Chimeric antigen receptors (CAR) are synthetic receptors engineered to target a user-defined antigen. They comprise an extracellular single-chain variable fragment for target recognition and intracellular signalling domains commonly derived from immune cells. CAR-T cells have proven to be successful in therapy of some cancers. CAR-T cells are activated upon antigen-priming and subsequent intracellular signalling. However, tonic signalling in CAR-T cells remains a challenge in developing CAR-T therapeutics of high efficacy as it causes early T-cell exhaustion, limiting therapeutic persistence. Moreover, a poor choice of target antigen leads to off-target cytotoxicity, often hampering the host's survival. In addition, conventional methods of delivering CAR gene circuits utilise viral vectors, such as lentiviruses and retroviruses, which insert the CAR gene circuits into transcriptionally active sites in the genome. This increases the risks of malignant transformation due to improper genome integration. Optimisation in CAR-T engineering, from the architecture of CAR gene circuits to the structure of CAR and the behaviour of CAR-T cells, is paramount to ensure high efficacy, persistence, and precision in CAR-T therapy. This review provides insights into engineering CAR-T cells for precision in cancer therapy by highlighting the key strategies recently developed to optimise the function and efficiency of CARs. The delivery method of CAR gene circuits, circuit and structural modification of CAR, T-cell phenotype manipulation and T-cell arming will be discussed to accentuate their interplay in regulating CAR-T therapy's safety, precision, and efficacy.

Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study.

This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 µg. After assessment of safety and immunogenicity of the 12 µg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 µg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3-73.3% across groups) and myalgia (36.9%; 13.3-56.7%). Unsolicited AEs were reported by 14.4% (6.7-26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7-30.0%) reported MAAEs, and 8.3% (0.0-13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.

What is the context? Since 2019, more than 776 million people have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, and more than 7 million people have died due to COVID-19.The virus changes over time and new variants may evade the protection provided by vaccines that are effective against previous variants.Therefore, it is necessary to develop vaccines that can be quickly updated to better protect against COVID-19 caused by new SARS-CoV-2 variants.We developed an mRNA vaccine, CV0501, that encodes a key protein on the surface of the SARS-CoV-2 Omicron BA.1 variant to instruct the immune system for future protection against COVID-19. The mRNA is encased in lipid nanoparticles that can increase the immune response to the vaccine.What is new? We administered different dose levels (that is, different amounts of mRNA) of CV0501 to adults who had previously been vaccinated at least twice with a different COVID-19 vaccine.We found that even at increased dose levels, CV0501 caused mostly mild side effects that resolved within a few days. Serious adverse events or events that required medical attention were not related to the vaccine.We also found that CV0501 generated immune responses not only against the Omicron BA.1 subvariant (vaccine antigen) but also against the original SARS-CoV-2 variant, the Delta variant, and other Omicron subvariants, at all dose levels tested.What is the impact? Our findings indicate that the CV0501 vaccine was well tolerated and induced immune responses against vaccine target variant as well as other SARS-CoV-2 variants.Other vaccines against COVID-19 based on the mRNA technology used for CV0501 will be further evaluated.

Potential tumor-specific antigens and immune landscapes identification for mRNA vaccine in thyroid cancer.

Background: Tumor mRNA vaccines have been identified as a promising technology for cancer therapy in multiple cancer types, while their efficacy in thyroid cancer (THCA) is unclear. Immunotyping is strongly associated with the immune microenvironment and immune status in cancer, thus it is important in vaccination and therapeutic response. This study is to identify potential valuable antigens and novel immune subtypes of THCA for immune landscape construction, thus screening patients suitable for mRNA vaccination. Methods: The clinical information and gene expression files of 568 THCA cases were obtained from the TCGA dataset. The DNA copy number variation and the somatic mutation of THCA were visualized by the cBioPortal database. TIMER was used to investigate the immune infiltrating correlation with candidate antigens. Consensus clustering analysis was conducted to cluster data using the ConsensusClusterPlus package. The immune landscapes of THCA patients were visualized using the Monocle package. The critical hub genes for THCA mRNA vaccines were identified by WGCNA package. To validate, the immunohistochemistry and real-time quantitative PCR (RT-qPCR) were performed to detect the expression level of potential antigen for mRNA vaccine in tissue and cell lines in THCA. Results: Thymidine kinase 1 (TK1) was identified as a potential biomarker of mRNA vaccine against THCA. It was confirmed to be significantly upregulated in THCA tissues and cells lines. Moreover, three novel immune subtypes of THCA were obtained based on the expression consistency of immune-associated genes. The S2 subtype was characterized as an immunological "cold" phenotype with a high expression of immunogenic cell death modulators. S1 and S3 subtypes were immunological "hot" phenotypes with immune checkpoints upregulation. Further, the immune landscape of THCA patients was visualized and ten hub genes for mRNA vaccines were identified. Conclusion: TK1 was a tumor-specific antigen of mRNA vaccines. The patients belonging to the S2 subtype ("cold" tumor) were suitable for mRNA vaccine therapy in THCA. Notably, ten hub genes were conducted as potential biomarkers for identifying suitable patients for mRNA vaccination. These findings provided novel insights into mRNA vaccine development against THCA.

A mathematical model simulating the adaptive immune response in various vaccines and vaccination strategies.

Vaccination has been widely recognized as an effective measure for preventing infectious diseases. To facilitate quantitative research into the activation of adaptive immune responses in the human body by vaccines, it is important to develop an appropriate mathematical model, which can provide valuable guidance for vaccine development. In this study, we constructed a novel mathematical model to simulate the dynamics of antibody levels following vaccination, based on principles from immunology. Our model offers a concise and accurate representation of the kinetics of antibody response. We conducted a comparative analysis of antibody dynamics within the body after administering several common vaccines, including traditional inactivated vaccines, mRNA vaccines, and future attenuated vaccines based on defective interfering viral particles (DVG). Our findings suggest that booster shots play a crucial role in enhancing Immunoglobulin G (IgG) antibody levels, and we provide a detailed discussion on the advantages and disadvantages of different vaccine types. From a mathematical standpoint, our model proposes four essential approaches to guide vaccine design: enhancing antigenic T-cell immunogenicity, directing the production of high-affinity antibodies, reducing the rate of IgG decay, and lowering the peak level of vaccine antigen-antibody complexes. Our study contributes to the understanding of vaccine design and its application by explaining various phenomena and providing guidance in comprehending the interactions between antibodies and antigens during the immune process.

Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus.

BACKGROUND: Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects. METHODS: We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV. FINDINGS: The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice. INTERPRETATION: Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines. FUNDING: National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.

Real-world assessment of immunogenicity in immunocompromised individuals following SARS-CoV-2 mRNA vaccination: a two-year follow-up of the prospective clinical trial COVAXID.

BACKGROUND: Immunocompromised patients with primary and secondary immunodeficiencies have shown impaired responses to SARS-CoV-2 mRNA vaccines, necessitating recommendations for additional booster doses. However, longitudinal data reflecting the real-world impact of such recommendations remains limited. METHODS: This study represents a two-year follow-up of the COVAXID clinical trial, where 364 of the original 539 subjects consented to participate. 355 individuals provided blood samples for evaluation of binding antibody (Ab) titers and pseudo-neutralisation capacity against both the ancestral SARS-CoV-2 strain and prevalent Omicron variants. T cell responses were assessed in a subset of these individuals. A multivariate analysis determined the correlation between Ab responses and the number of vaccine doses received, documented infection events, immunoglobulin replacement therapy (IGRT), and specific immunosuppressive drugs. The original COVAXID clinical trial was registered in EudraCT (2021-000175-37) and clinicaltrials.gov (NCT04780659). FINDINGS: Several of the patient groups that responded poorly to the initial primary vaccine schedule and early booster doses presented with stronger immunogenicity-related responses including binding Ab titres and pseudo-neutralisation at the 18- and 24-month sampling time point. Responses correlated positively with the number of vaccine doses and infection. The vaccine response was blunted by an immunosuppressive state due to the underlying specific disease and/or to specific immunosuppressive treatment. INTERPRETATION: The study results highlight the importance of continuous SARS-CoV-2 vaccine booster doses in building up and sustaining Ab responses in specific immunocompromised patient populations. FUNDING: The present studies were supported by the European Research Council, Karolinska Institutet, Knut and Alice Wallenberg Foundation, Nordstjernan AB, Region Stockholm, and the Swedish Research Council.

Vaccine skepticism and vaccine development stages; inoculation from "cowpox" lesion to the current mRNA vaccine of COVID-19: review.

Global pandemics can be tackled by two means: lockdowns and vaccinations. As vaccination has a low impact on economic outcomes and better acceptance by people, it is the preferred method by most governments as a medium- to long-term solution. Vaccines have played a significant role in reducing the global burden of infectious diseases. They are designed to teach the immune system how to fight a particular infection before it causes a disease in subsequent exposures by creating a memory. Although vaccines effectiveness is well known, anti-vaccination movements pose significant challenges, even in high-income settings, leading to outbreaks of life-threatening infectious diseases. Hesitancy to take vaccines is not new and began with the first vaccination of smallpox. At that time, the problem was solved by a regulatory obligation to take vaccines, declared in England and Wales in 1853, which eventually led to its eradication in 1980. Different studies show that there is a decline in awareness of vaccines, hesitancy to take them, and concerns and trust issues regarding healthcare professionals. These problems have been rising over the past few decades for several reasons, notably, because of misinformation spread by social media. Therefore, the objective of this review is to provide a brief overview about vaccine hesitancy and attributable factors, illustrate the different types of vaccines, show the major challenges of vaccine development, and illustrate the pros and cons of each type.

Hesitancy to take vaccines and stages of vaccine development starting from the first vaccine; inoculation from "cowpox" wound to the current mRNA vaccine of COVID-19: Review Global pandemics can be tackled by two means: lockdowns and vaccinations. As vaccination has a low impact on economic outcomes, it is the preferred method by most governments as a medium- to long-term solution. Vaccines play a significant role in reducing the global burden of infectious diseases. They are designed to teach our body defense mechanism how to fight a particular infection before it causes a disease in subsequent infections by creating a memory. Although its effectiveness is well known, anti-vaccination movements pose many challenges, even in high-income settings, leading to outbreaks of life-threatening infectious diseases. Vaccine hesitancy is not new and began with the first vaccination of smallpox. At that time, the problem was solved by a regulatory obligation to take vaccines, declared in England and Wales in 1853, which eventually led to its eradication in 1980. Different studies show that there is a decline in awareness of vaccines, hesitancy to take them, and concerns and trust issues regarding healthcare professionals. These problems have been rising over the past decades for a number of reasons. Therefore, the objective of this review is to provide a brief overview of the different types of vaccines, show the major challenges of vaccine development, and illustrate the pros and cons of each type.

Clinical Manifestations and Adverse Cardiovascular Events in Patients with Cardiovascular Symptoms after mRNA Coronavirus Disease 2019 Vaccines.

PURPOSE: The number of patients presenting with vaccination-related cardiovascular symptoms after receiving mRNA vaccines (mRNA-VRCS) is increasing. We investigated the incidence of vaccine-related adverse events (VAEs), including myocarditis and pericarditis, in patients with mRNA-VRCS after receiving BNT162b2-Pfizer-BioNTech and mRNA-1273-Moderna vaccines. MATERIALS AND METHODS: We retrospectively collected data on patients presenting with mRNA-VRCS who visited the outpatient clinic of two tertiary medical centers. Clinical characteristics, laboratory findings, echocardiographic findings, and electrocardiographic findings were evaluated. VAE was defined as myocarditis or pericarditis in patients after mRNA vaccination. Clinical outcomes during short-term follow-up, including emergency room (ER) visit, hospitalization, or death, were also assessed among the patients. RESULTS: A total of 952 patients presenting with mRNA-VRCS were included in this study, with 89.7% receiving Pfizer-BioNTech and 10.3% receiving Moderna vaccines. The mean duration from vaccination to symptom was 5.6±7.5 days. VAEs, including acute myocarditis and acute pericarditis, were confirmed in 11 (1.2%) and 10 (1.1%) patients, respectively. The VAE group showed higher rates of dyspnea, echocardiography changes, and ST-T segment changes. During the short-term follow-up period of 3 months, the VAE group showed a higher hospitalization rate compared to the control group; there was no significant difference in ER visit (p=0.320) or mortality rates (p>0.999). CONCLUSION: Amongst the patients who experienced mRNA-VRCS, the total incidence of VAEs, including acute myocarditis and pericarditis, was 2.2%. Patients with VAEs showed higher rates of dyspnea, echocardiographic changes, and ST-T segment changes compared to those without VAEs. With or without the cardiovascular events, the prognosis in patients with mRNA-VRCS was favorable.

Personalized mRNA vaccines in glioblastoma therapy: from rational design to clinical trials.

Glioblastomas (GBMs) are the most common and aggressive malignant brain tumors, presenting significant challenges for treatment due to their invasive nature and localization in critical brain regions. Standard treatment includes surgical resection followed by radiation and adjuvant chemotherapy with temozolomide (TMZ). Recent advances in immunotherapy, including the use of mRNA vaccines, offer promising alternatives. This review focuses on the emerging use of mRNA vaccines for GBM treatment. We summarize recent advancements, evaluate current obstacles, and discuss notable successes in this field. Our analysis highlights that while mRNA vaccines have shown potential, their use in GBM treatment is still experimental. Ongoing research and clinical trials are essential to fully understand their therapeutic potential. Future developments in mRNA vaccine technology and insights into GBM-specific immune responses may lead to more targeted and effective treatments. Despite the promise, further research is crucial to validate and optimize the effectiveness of mRNA vaccines in combating GBM.

Erythroderma Following Pfizer-BioNTech COVID-19 Vaccination in a Patient With Atopic Dermatitis: A Case Report.

Cutaneous adverse reactions to mRNA COVID-19 vaccines in patients with preexisting dermatologic disease include bullous eruptions, pityriasis rubra pilaris, dermatomyositis, and granuloma annulare. Erythroderma is a rare but severe adverse reaction not previously seen. This case report describes the development of erythroderma in a 73-year-old male with a history of atopic dermatitis, with widespread erythema and scaling covering 95% of his body surface area, which developed sequentially after receiving each dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccination. The patient's condition improved significantly with appropriate dermatologic treatment, including systemic and topical corticosteroids and dupilumab. Thus, it is imperative to recognize erythroderma as a potential side effect of the Pfizer-BioNTech COVID-19 vaccine, particularly in patients with preexisting dermatologic conditions. Early diagnosis and treatment are vital for managing this potentially life-threatening reaction and preventing severe complications.