Retrospective review of vaccination status in patients with newly diagnosed chronic lymphocytic leukaemia

Introduction: Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of infection. CLL is associated with a secondary immunodeficiency and impaired response to vaccination. Recent British Society of Haematology guidelines recommend that patients with CLL should receive vaccination against pneumococcal infection at diagnosis, an annual influenza vaccine and COVID-19 vaccination. Patients aged 70-79 years should also receive the Shingrix vaccine. Patients with CLL should not receive live vaccines. In response to this guideline, a letter detailing vaccination requirements was created for patients to give to their general practitioner (GP). The local process for vaccination referral has since changed. Previously, vaccination requirements were communicated to the GP via letter. There is now a dedicated Vaccination Hub to which clinicians can directly refer patients for appropriate vaccinations. Aim(s): The aim of this project was to assess vaccination referral and vaccination status in patients with newly diagnosed CLL. Method(s): All new diagnoses of CLL from 2021 to 2022 were identified by review of the Haematology Multi-Disciplinary Team meeting electronic registration forms. Electronic patient records were reviewed to determine vaccination referral completion and vaccination status. Result(s): A total of 29 patients were identified as new diagnoses of CLL. Seventeen patients were diagnosed in 2021 and 12 in 2022. Sixty-nine percent of the patients were male and the average age was 70.9 years. Vaccination was discussed with 11 patients (38%) and 10 patients (34%) were referred for vaccination. Eleven patients (38%) had never received a pneumococcal vaccine. Nine patients (31%) had previously received the vaccine but not within the past 5 years. Five patients (17%) patients had received one dose of Pneumovax 23 following referral. No patients had received the initial Prevenar 13 vaccine. Twelve patients (41%) had not received an influenza vaccine. Of those who had received the vaccine, the majority (70%) had received this routinely. Similarly, 71% of patients had received the COVID-19 vaccine routinely as opposed to three patients who received this postreferral. Of those who were eligible, 50% had received the Shingrix vaccine. Conclusion/Discussion: Local rates of vaccination in patients with CLL are low. Numbers were too small to allow for comparison between the methods of referral. Of those referred, not all received the appropriate vaccinations. Further work is therefore required to improve both the number and completion of the referrals. Future steps will include local teaching on vaccinations in CLL and the referral pathway.

Cuban Vaccines Abdala and Mambisa against Covid-19

Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023

Sars-Cov-2 Vaccine from Infected Plant Attenuated Virus Using Acer Cincinatum (Vine Maple)

Purpose of study Proposal for an oral (or if required, parenteral) COVID-19 vaccination based upon this described technology. Investigational theory under study for the past 9 months of COVID-19 growing season. Coronavirus can attack and infect plant species. It was found that SARS-CoV-2 can infect various plant species. Others have found plants, for example tobacco as a good growth medium for Coronavirus and SARS-CoV-2. This current study has found various plants species infected with SARS-CoV-2 by rPCR. As the plants were located beside a well used hiking trail for humans, and were infected along the trail including various species with SARS-CoV-2, hypothesized that human airborne contact had caused infection in the bordering plants. Humans were observed to be coughing while walking on the trail, and were not wearing masks. The plant leaves developed small circular colonies of the virus, which became self-limited at several millimeters in diameter. All of the plants were clear of these lesions before the COVID-19 Pandemic. The plants 'immune' system produced antiviral agents, including lectins which limited the growth of the colonies and prevent death of the leaf and whole plant. The fungal cultures of the 'spots' were negative. The rPCR of all spots tested in the present series was positive for SARS-CoV-2. Hypothesis, that self-augmentation of the virus occurred by the natural culturing in plant leaves that produce antiviral agents as part of their 'immune system.' Hypothesis, a symbiotic type relationship developed between the plant using its chemical immune system, and the virus allowed to replicate in an augmented fashion to allow both the virus and the host to survive and grow. As the top candidates for the oral vaccine are nontoxic, hypothesis involves the maceration of the infected leaves, mixing with a nontoxic adjuvant and flavoring to promote assimilation and palatability, with the proposed route of entry being mastication, thus exposing the oral-nasal mucosa to the vaccine, with the probable best of immunity to usual exposure to the SARS-CoV-2 virus, that is the oral-nasal mucosal and upper airway route. As many types of animals are now infected with SARS-CoV-2, it is further hypothesized that this oral vaccine could also be mass produced to add to various animals by feedstock and oral route. Methods used Hypotheses formed through observations. Testing of observations by pPCR, viral cell culture, fungal culture, light and electron microscopy. Summary of results pPCR SARS-CoV-2 positive, cell culture 'lysis experiment' positive, EM and light microscopy positive, fungal culture negative. Conclusions TABLE OF HYPOTHESES AND STUDY RESULTS (HYPOTHETICAL, OBSERVED, PROVEN) 1. The first hypothesis that the virus is attenuated by the plant, using its innate chemical immune system. Similarly, Pasteur used chemical such as phenol to attenuate viruses for wome of the first successful vaccines. Observed. 2. Hypothesis, the plants 'immune' system produced antiviral agents, including lectins, flavonoids, and others, which limited the growth of the colonies and prevent death of the leaf and whole plant. Proven. 3. Hypothesis is that the nontoxic plants, such as Vine Maple sp.(Acer cincinatum), could be used to produce and oral plant attenuated vaccine. Hypothesis. 4. Hypothesis involves the maceration of the infected leaves, mixing with a nontoxic adjuvant and flavoring to promote assimilation and palatability, with the proposed route of entry being mastication, thus exposing the oral-nasal mucosa to the vaccine, with the probable best of immunity to usual exposure to the SARS-CoV-2 virus, that is the oral-nasal mucosa, upper airway. (Figure Presented).

Regulatory Framework: Vaccine Development in Us, India and Eu

Vaccine development usually takes around 7 y to come to the market after getting necessary regulatory approvals. But recent pandemics like Covid, Ebola, Swine Flu, have resulted in the collaboration of efforts between the government doing investments in vaccine development, academia, regulatory bodies, and industry. This has shortened the timelines for approval for vaccines. In 2009, HINI, Swine flu vaccines took 93 d for identifying the vaccine candidate for clinical trials. In 2014, for Ebola vaccine, it was deployed while the epidemic was still going on. Ebola vaccine was developed in 5 y. In case of Covid (SARS-CoV-2) clinical trials were approved when 2 mo of the pandemic onset. Within a time of 9 mo about 138 vaccine candidates are being reviewed for approval of EUA. This highly helps in the shortening of vaccine development and necessary approval. In this paper, we focused on the regulatory framework of vaccine development in INDIA, US and EU.Copyright © 2023 The Authors.

History, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19)

The Coronavirus Disease 2019 (COVID-19), also known as a novel coronavirus (2019-n-CoV), reportedly originated from Wuhan City, Hubei Province, China. Coronavirus Disease 2019 rapidly spread all over the world within a short period. On January 30, 2020, the World Health Organization (WHO) declared it a global epidemic. COVID-19 is a Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) evolves to respiratory, hepatic, gastrointestinal, and neurological complications, and eventually death. SARS-CoV and the Middle East Respiratory Syndrome coron-avirus (MERS-CoV) genome sequences similar identity with 2019-nCoV or Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). However, few amino acid sequences of 2019-nCoV differ from SARS-CoV and MERS-CoV. COVID-19 shares about 90% amino acid sequence simi-larity with SARS-CoV. Effective prevention methods should be taken in order to control this pandemic situation. To date, there are no effective treatments available to treat COVID-19. This review provides information regarding COVID-19 history, epidemiology, pathogenesis and molecular diagnosis. Also, we focus on the development of vaccines in the management of this COVID-19 pandemic and limiting the spread of the virus.Copyright © 2022 Bentham Science Publishers.

COVID-19 Vaccines: Fabrication Techniques and Current Status

The year 2020 was the most challenging period due to the havoc caused by the outbreak of novel coronavirus SARS-CoV-2. Scientists and researchers all around the world have endeav-ored every possible approach to find solutions in context to therapeutics and vaccines to control the spread of this life-threatening virus. The acceleration instigated by the outbreak of SARS-CoV-2 and its mutated strains has leveraged the use of numerous platform technologies for the development of vaccines against this unfathomable disease. Vaccines could play an important role in miti-gating the effects of COVID-19 and reducing the ongoing health crisis. Various innovative plat-forms like proteins, nucleic acids, viruses, and viral vectors have been exploited to fabricate vaccines depicting almost 90% of efficacy like BNT162b2, AZD1222, Ad5-nCoV, etc. Some of these vaccines are multipotent and have shown potent activity against newly emerged malicious strains of SARS-CoV-2 like B.1.351 and B.1.1.7. In this review article, we have gathered key findings from various sources of recently popularized vaccine candidates, which will provide an overview of potential vaccine candidates against this virus and will help the researchers to investi-gate possible ways to annihilate this menace and design new moieties.Copyright © 2022 Bentham Science Publishers.

Boosting compromised SARS-CoV-2-specific T cell immunity in liver transplant recipients by mRNA vaccination

Background and aims Liver transplant recipients (LTR) are threatened by a lower immunogenicity of SARS-CoV-2 mRNA vaccines. However, the interplay between the different branches of the adaptive immune system especially after a third (and fourth) vaccine dose is still poorly understood. Methods Our study longitudinally compares the humoral as well as the cellular response between age-matched LTR (n = 24) and healthy controls (HC, n = 19) after three to four vaccine doses. Therefore, we assessed antibody titers, analyzed the spike-specific T cell epitope repertoire, performed an in-depth characterization of spike-specific CD8 + T cells on a single-epitope level and examined the distribution of different virus-specific CD4 + T cell subpopulations. Results Compared to HC, the development of high antibody titers depended on a third vaccine dose in most LTR. In contrast, spike-specific CD8 + T cells reached a stable level already after the second vaccine dose, albeit with a lower frequency and a narrower epitope repertoire compared to HC. Concerning the CD4 + T cells, the total number of detectable responses as well as the repertoire of targeted epitopes within the spike protein did not signifcantly difer in both cohorts. However, we observed a link between the overall attenuated vaccine response and a reduced frequency of spike-reactive follicular T helper cells (TFH) in LTR. Conclusion Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most LTR. Evaluations of additional booster doses may thus consider the individual vaccine responsiveness as well as the evolution of novel variants of concern.

Biological documentation in primary care: a review from the dermatology department of a Welsh hospital

Biological therapies are increasingly being used in dermatology to treat conditions such as psoriasis and eczema. These medications are prescribed and dispensed in secondary care;however, it is important that they are present in the patient's primary care record, as this is often used by both the primary care provider and the hospital clerking doctor when the patient presents with other health concerns. Biologics are immunosuppressive medications, and it is thus important that any practitioner treating a patient who has been prescribed them is aware of this. Using a departmental record, all patients prescribed biological therapies or subcutaneous methotrexate were identified (n = 157). Their primary care medication record was then interrogated to assess whether the biological therapy was recorded. Forty-five (29%) patients on biological therapies or subcutaneous methotrexate did not have this recorded on their general practitioner (GP) record. The most common medications not recorded were ustekinumab (n = 14) and dupilumab (n = 13). There was no clear pattern indicating that a particular GP surgery was recording these medications poorly, and the patients were cared for evenly between the dermatology consultants in the department. This brief piece of work demonstrates that there is a problem with these prescriptions being accurately recorded on the GP record. Almost one-third of patients in the department did not have their biological therapy listed on their primary care record. Practitioners must be aware that a patient is on an immunosuppressive medication, especially when diagnosing and treating infections and assessing patient priority for COVID-19 vaccination, as well as including the need to avoid live vaccines. Furthermore, the GP record was used by Welsh Government agencies to identify patients needing to shield during the COVID-19 pandemic. These 45 patients recognized in the study would not necessarily have been identified as potentially high risk (depending on other comorbidities) and may therefore not have been advised to shield (in line with British Association of Dermatologists guidance for self-isolation and immunosuppressed patients). To rectify this problem in the short term, each GP surgery was contacted regarding the particular patients identified and were advised to add their biological therapy to their primary care record. Discussions between primary and secondary care and pharmacy are ongoing in order to identify how to prevent this problem from continuing.

Viral vector vaccines: ef forts to develop vaccines against emerging infectious diseases.

Vaccines are one of the most effective means of preventing viral infections. Since Edward Jenner invented the world's first vaccine in 1796, against smallpox, various types of vaccine have been DDS developed, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, viral vector vaccines and nucleic acid vaccines. Viral vector vaccines and nucleic acid vaccines mRNA vaccines and DNA vaccineshave been developed most recently. In these vaccines, genes encoding viral proteins that serve as antigens are introduced into the body. The viral vector is an excellent vaccine delivery system that efficiently delivers antigen genes to target cells, and has been utilized for vaccine development against a variety of emerging infectious diseases, including AIDS, malaria, Ebola hemorrhagic fever, dengue fever, and most recently COVID-19 . Here, we provide an overview of viral vector vaccines and discuss recent efforts to develop vaccines against emerging infectious diseases.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Current pandemic COVID-19 vaccine strategies and development: a comprehensive review

The coronavirus disease-19 pandemic with the characteristics of asymptomatic condition, long incubation period and poor treatment has influenced the entire globe. Coronaviruses are important emergent pathogens, specifically, the recently emerged sever acute respiratory syndrome coronavirus 2, the causative virus of the current COVID-19 pandemic. To mitigate the virus and curtail the infection risk, vaccines are the most hopeful solution. The protein structure and genome sequence of SARS-CoV-2 were processed and provided in record time;providing feasibility to the development of COVID-19 vaccines. In an unprecedented scientific and technological effort, vaccines against SARS-CoV-2 have been developed in less than one year. This review addresses the approaches adopted for SARS-CoV-2 vaccine development and the effectiveness of the currently approved vaccines.Copyright © 2023, Finlay Ediciones. All rights reserved.

Traditional and Recent Approaches for the Development of Animal Vaccines. A Review

Objective: To show new trends in the field of vaccinology and spread awareness among population regarding vaccination of animals and successfully controlling spread of diseases Study Design: This is a review study for the development of animal vaccines and was conducted from September, 2021 to June, 2022 at IMBB Department, The University of Lahore, Lahore, Pakistan. Review of Literature was collected on traditional and recent approaches for the development of veterinary vaccines and gathered for the awareness among the field of veterinary vaccinology. Methodology: Animals provide food and clothing in addition to other value-added products. Changes in diet and lifestyle have increased the consumption and the use of animal products. Infectious diseases in animals are a major threat to global animal health and its welfare;their effective control is crucial for agronomic health, for safeguarding food security and also alleviating rural poverty. Development of vaccines has led to increased production of healthy poultry, livestock, and fish. Animal production increases have alleviated food insecurity. Before year 2000, most veterinary vaccines were from inactivated organisms that were formulated with an oil-based adjuvant or live attenuated vaccines. Result(s): The discovery of antigen/gene delivery systems has facilitated the development of novel prophylactic and therapeutic veterinary vaccines. Uses several bioinformatics algorithms to predict antigen localization and it has been successfully applied to immunize against many veterinary diseases. Vectors and pathogens that may lead to emergent diseases in animals. Preventing transmission of emerging infectious diseases at the animal-human interface is critically important for protecting the world population from epizootics and pandemics. Hence, there is a need to develop new vaccines to prevent diseases in animals. An area of veterinary vaccination that needs more research and discussion is vaccine interference. The phrase itself is ambiguous and might mean either a condition in which immunization against one disease may weaken the protective immunity established by immunization against another, or a circumstance in which the presence of maternally derived antibodies prevent immunization in newborn animals. Practical implication: This study will provide awareness among community about veterinary vaccines and will develop a disease-free state for pets.Vetrinary vaccines not only prevent diseases in animals but also stops their spread among humans. Conclusion(s): This review examines some of the main topics that have emerged in the veterinary vaccine field with the use of modern biotechnology techniques. In addition, development of effective vaccines has led to healthier companion animals. However, challenges remain including climate change that has led to enhancement in vectors and pathogens that may lead to emergent diseases in animals. Preventing transmission of emerging infectious diseases at the animal-human interface is critically important for protecting the world population from epizootics and pandemics. Hence, there is a need to develop new vaccines to prevent diseases in animals.Copyright © 2022 Lahore Medical And Dental College. All rights reserved.

Cold-adapted SARS-CoV-2 variants with different temperature sensitivity exhibit an attenuated phenotype and confer protective immunity.

As novel SARS-CoV-2 Variants of Concern emerge, the efficacy of existing vaccines against COVID-19 is declining. A possible solution to this problem lies in the development of a live attenuated vaccine potentially able of providing cross-protective activity against a wide range of SARS-CoV-2 antigenic variants. Cold-adapted (ca) SARS-CoV-2 variants, Dubrovka-ca-B4 (D-B4) and Dubrovka-ca-D2 (D-D2), were obtained after long-term passaging of the Dubrovka (D) strain in Vero cells at reduced temperatures. Virulence, immunogenicity, and protective activity of SARS-CoV-2 variants were evaluated in experiments on intranasal infection of Syrian golden hamsters (Mesocricetus auratus). In animal model infecting with ca variants, the absence of body weight loss, the significantly lower viral titer and viral RNA concentration in animal tissues, the less pronounced inflammatory lesions in animal lungs as compared with the D strain indicated the reduced virulence of the virus variant. Single intranasal immunization with D-B4 and D-D2 variants induced the production of neutralizing antibodies in hamsters and protected them from infection with the D strain and the development of severe pneumonia. It was shown that for ca SARS-CoV-2 variants, the temperature-sensitive (ts) phenotype was not obligate for virulence reduction. Indeed, the D-B4 variant, which did not possess the ts phenotype but had lost the ability to infect human lung cells Calu-3, exhibited reduced virulence in hamsters. Consequently, the potential phenotypic markers of attenuation of ca SARS-CoV-2 variants are the ca phenotype, the ts phenotype, and the change in species specificity of the virus. This study demonstrates the great potential of SARS-CoV-2 cold adaptation as a strategy to develop a live attenuated COVID-19 vaccine.

Subcutaneous nivolumab versus intravenous nivolumab in patients with previously treated, advanced, or metastatic clear cell renal cell carcinoma

Background: Nivolumab (NIVO), a programmed death-1 immune checkpoint inhibitor, has demonstrated clinical efficacy across patients with different tumor types, including clear cell renal cell carcinoma (ccRCC), when administered via IV infusion. As an alternative to IV infusion, subcutaneous (SC) administration alleviates the need for IV ports, thereby lowering the risk of associated complications such as infections and phlebitis. SC formulation also reduces the time for dose preparation and administration, which may decrease overall treatment burden and reduce patient time in the clinic, benefiting patients and healthcare providers and improving overall healthcare resource utilization. SC-administered NIVO consists of NIVO co-formulated with the recombinant human hyaluronidase PH20 enzyme (NIVO + rHuPH20), which aims to increase the dispersion and absorption of NIVO within the SC space. SC NIVO + rHuPH20 was shown to be safe and well tolerated in a phase 1/2 study, warranting further investigation (Lonardi S et al. J Clin Oncol 2021;39(suppl 15):2575). Methods: CheckMate 67T is a multicenter, randomized, open-label, phase 3 study that will evaluate the noninferiority of SC NIVO + rHuPH20 versus IV NIVO in patients with advanced or metastatic ccRCC who have progressed after receiving ≤ 2 prior systemic treatment regimens. Key inclusion criteria are age ≥ 18 years, histologically confirmed advanced or metastatic ccRCC, measurable disease by RECIST v1.1 within 28 days prior to randomization, and a Karnofsky performance status ≥ 70. Key exclusion criteria are untreated symptomatic metastases to the central nervous system, other malignancy, autoimmune diseases, HIV-positive status with AIDS-defining infection within past year or current CD4 count < 350 cells/μL, other serious or uncontrolled disorders including severe, acute SARS-CoV-2 infection, and prior treatment with immune checkpoint inhibitors, other T-cell-targeting antibody drugs, or live attenuated vaccines within 30 days of first study treatment. At least 454 eligible patients will be randomized to receive SC NIVO + rHuPH20 or IV NIVO. The primary objectives are to demonstrate pharmacokinetic (PK) noninferiority of SC NIVO versus IV NIVO, as measured by time-averaged serum concentration over the first 28 days (Cavgd28) and trough serum concentration at steady state (Cminss) (co-primary endpoints). Secondary endpoints include objective response rate by blinded independent central review, additional PK parameters, safety, efficacy, and immunogenicity of SC NIVO and IV NIVO. This study is currently enrolling patients globally.

Multiparametric CMR Findings in Mrna COVID-19 Vaccine-induced Myocardit is: A Case Series

Introduction: Within weeks of the pediatric coronavirus disease 2019 (COVID-19) vaccination campaign beginning, reports of acute myocarditis after adolescents' second vaccination began. The present research describes the clinical and cardiovascular magnetic resonance (CMR) imaging characteristics of three adolescents recently vaccinated with a mRNA vaccine and admitted for myopericarditis treatment. Case Description: This retrospective case-series investigated adolescents admitted within a week of their second mRNA COVID-19 vaccination. The electronic medical record was queried for all patients ≥12 years old, admitted for acute myocarditis or pericarditis (International Classification Diseases-Version 10;I30.xx, I40.xx respectively) since April 1, 2021. Patients were included if they had a documented mRNA vaccination in the prior seven days. Three patients met inclusion criteria. All three had acute onset chest pain within 48 hours of receiving their second mRNA vaccine. All had elevated troponins, all were eventually admitted and had mild clinical courses. All met Lake Louise criteria for acute myocarditis despite only one patient having mild depression of cardiac function on echocardiography. All patients were negative for COVID-19 and none had a clinical history or immunologic evidence of prior COVID-19. The patient with the most diffuse pattern of late gadolinium enhancement on CMR (Figure 1) developed ventricular tachycardia three weeks after discharge. Discussion: Vaccine induced myopericarditis is rare in inactivated vaccines, but is a known entity with live vaccines, especially the smallpox vaccine. Since the 1950's, cases of myocarditis and pericarditis have been reported in association with vaccination. Research using VAERS has previously found that from 1990- 2018, 0.1% of reports were for myopericarditis associated with vaccination. The rates of mRNA vaccine-induced myocarditis are currently unknown, but our clinical findings are similar to other recently published case series of pediatric mRNA associated myopericarditis. We have observed differences in CMR patterns between our patients from this series and previous reports of patients with cardiac involvement from COVID-19 (Table 1). We remain uncertain regarding the precise pathophysiology in these patients with myocardial inflammation following mRNA vaccine administration. However, the relatively focal pattern of involvement, and the relative preservation of global function, suggest a milder involvement of the myocardium-in most of these patients-than has previously been observed in classic viral and COVID-19 myocarditis. Conclusion: Three adolescent males developed acute myocarditis within days of their second mRNA COVID-19 vaccination. CMR in combination with serum troponin measurements was critical for diagnosis, and arrythmia monitoring was critical in their follow up. Repeat CMR studies over the six months following diagnosis will be important to rule out development of post-inflammatory fibrosis and long-term arrhythmias. Legend: A and B: LGE (Magnitude IR) and PSIR (Phase sensitive IR), respectively, showing patchy epicardial enhancement at the basal inferolateral and inferior segments;C: Abnormal ECV at basal anterolateral, inferolateral and inferior segments;D and E: ECV and T1 bullseye maps with abnormal values;F and G: Patchy visible edema at basal inferolateral, anterolateral and inferior segments on the T2 and T2 color map;H: Bullseye map showing T2 values;I: Asymmetric Right axillary lymphadenopathy secondary to vaccination in the right arm.

Vaccinations and travel for patients with IBD

Patients with chronic inflammatory bowel disease (IBD) are at increased risk of an infectious disease due to their underlying disease and the often necessary immunosuppressive therapy. Many infectious diseases can be avoided through a consistent vaccination program. However, the vaccination status of many IBD patients deviates significantly from official recommendations. Therefore, the vaccination certificate should be checked at the first contact and then ideally annually at the time of influenza vaccination. Individualized immunosuppressive therapy allows many IBD patients to live a life with few or no symptoms, and many patients want to travel. All of these topics usually only played a minor role in the IBD consultation hours, but have clearly come to the fore with the beginning of the SARS-CoV-2 pandemic. In this article we would therefore like to give an overview of what is new and interesting about vaccinations, vaccine-preventable diseases, and travel.

Autoimmune diseases and vaccination against coronavirus disease 2019

There is not yet sufficient evidence that autoimmune disease (AID) increases susceptibility to coronavirus disease 2019 (COVID-19);however, AID can induce organ damage, cardiovascular and respiratory disease, and the use of multiple immunosuppressants in treatment may increase the risk of adverse outcomes following COVID-19 infection in patients with AID. Prevention strategies for COVID-19 should be prioritized in patients with AID, and COVID-19 vaccination may be a useful route. The benefits of COVID-19 vaccination in AID patients with stable disease activity outweigh the potential risks. The mRNA vaccine, inactivated vaccine and recombinant protein subunit vaccine are currently recommended for patients with AID, but recombinant adenoviral vector vaccines should be administered only when the benefits outweigh the risks in a comprehensive assessment, and live attenuated vaccines should be avoided. Most AID-therapeutic drugs have little effect on the immune response to COVID-19 vaccines and can be used normally during the vaccination period, while some drugs, such as methotrexate and rituximab, may reduce the immune response to COVID-19 vaccine and the timing of vaccination should be adjusted. This article discusses the necessity, safety and precautions of COVID-19 vaccination in patients with AID based on the existing clinical guidelines, expert consensus and literature studies.

IMMUNOGENICITY AND SAFETY OF STANDARD AND THIRD DOSE SARS-COV-2 VACCINATION IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES;A PROSPECTIVE COHORT STUDY

Introduction: The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods & Aims: This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARSCoV- 2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results: a total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40-63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32-55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls were responders, p<0,001. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192-4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p<0,001. Response was shown in ≤90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in £ 80% for JAK inhibitors (78%), and abatacept (53%) (fig.1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion: Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients. (Figure Presented) Fig.1 Anti-SARS-CoV-2 IgG antibodies following standard two dose SARS-CoV-2 vaccination according to medication group, compared to healthy controls. Violin plot showing the probability density of the data at different values, smoothed by a kernel density estimator. Each data point is a participant, and the solid orange line show the group median. The last row (CTRL vs) shows p-values for a comparison (Mann-Whitney U test) of anti-SARS-COV 2 antibodies between medication groups and healthy controls. ACE=Angiotensin converting enzyme, FL=full length, CTRL=Controls, TNF=Tumor necrosis factor inhibitor, TNF+= Tumor necrosis factor inhibitor combination therapy, MTX=methotrexate, VDZ=vedolizumab, JAK=Janus kinase inhibitor, TCZ=tocilizumab, UST=ustekinumab, ABA=abatacept, SCK=secukinumab.

Progress in research on mRNA vaccine and its mechanism

At present, Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 still spreads worldwide, bring great health risk and economic burden. Vaccination is an important measure to prevent and control the spread. The mRNA vaccines introduce the mRNAs encoding antigen protein into human body and translate directly to form the corresponding antigen protein thus induce specific immune response. As one of the nucleic acid vaccines of the third generation after inactivated vaccine, live attenuated vaccine, subunit vaccine and viral carrier vaccine, mRNA vaccines have characteristics of rapid response to pathogen variation, simple production process and easy scale expansion. This reviews the progress in research on immunological characteristics, molecular design, delivery system and safety as well as the relevant mechanisms.