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Background: The infection caused by the SARS-CoV-2 continues affecting millions of people worldwide and vaccines to prevent the coronavirus disease (COVID-19) are considered the most promising approach for curbing the pandemic. Otherwise, cardiovascular and neurological complications associated with the vaccines were speculated and some few case reports were published. Objective(s): We describe a case of postural orthostatic tachycardia syndrome (POTS) after viral vector COVID-19 vaccination and the possible autoimmune process of the syndrome. Method(s): A 35-year-old female, without previous symptoms or comorbidities, developed intermittent palpitation, intense fatigue and dyspnea, compromising her daily activities, triggered by upright position, seven days following the second dose of the Oxford vaccine. Physical examination was normal, except for a heart rate (HR) increase of 33 beats/min from supine to standing position, with no significant change in blood pressure and reproduction of symptoms. Result(s): A 24-hour Holter monitoring revealed episodes of spontaneous sinus tachycardia correlated with palpitation and fatigue. Extensive diagnostic investigations excluded primary cardiac, endocrine, infectious and rheumatologic etiologies. The patient underwent an autonomic function test which demonstrated normal baroreflex sensitivity, as well as normal cardiovagal and adrenergic scores. Head-up tilt test showed persistent orthostatic tachycardia (HR increase from a medium of 84 beats/min in supine position to 126 beats/min during upright tilt), without hypotension, consistent with the diagnostic criteria for POTS. According to the current guidelines, general behavior recommendations, pharmacotherapy with low dose of propranolol associated with the autonomic rehabilitation were oriented. Along three months of follow-up, the patient reported a gradually improvement in her symptoms. Conclusion(s): POTS is a heterogeneous disorder of the autonomic nervous system characterized by orthostatic tachycardia associated with symptoms of orthostatic intolerance. Although the physiopathology of COVID-19 vaccine and autonomic disorders remains speculative, autoimmune response is one of the possible mechanisms. Based on clinic presentation, the time frame of symptom onset is consistent with other well-known post-vaccination syndromes, which may be an indicator of an autoimmune process induced by immunization. Further studies are needed to assess causal relationship between immunization and autonomic dysfunction.Copyright © 2023
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COVID-19 mRNA vaccines: COVID-19 pandemic has made an extraordinary impact on global vaccine technology platform developments. Never in human history have there at least 6 vaccine platforms including: inactivated, protein subunit, VLP and other 3 new platforms i.e., mRNA, viral vector, and DNA, with more than 160 vaccine candidates being developed and tested in clinical trials. Nonetheless, among these several vaccine platforms, mRNA vaccine has been proven to be one of the most effective vaccines against COVID-19. There are two mRNA vaccines authorized for emergency use within a year and currently more than 20 mRNA vaccines are in clinical trials. The main advantages of mRNA vaccines are that they are speedily to design and develop, induce strong antibody and T-cell responses, manufacturing faster and at a lower cost. However, one of the major limitations is that it must be stored in cold temperatures. Currently more than billion doses of COVID-19 mRNA vaccines have been given globally. mRNA vaccines will be a key platform for next pandemics preparedness, it is therefore establishing this platform in various regions and LMICs is critical. Beyond COVID-19: A number of viral and cancer mRNA vaccines have been developing even before COVID-19. At least 12 mRNA vaccines against various infectious diseases are now in clinical evaluation, including Chikungunya virus, Cytomegalovirus, Epstein-Barr virus, Human metapneumovirus and parainfluenza virus type3, HIV, Influenza, Nipah, Rabies, Lasa, RSV, Zika, Varicella-zoster virus. Only few are entering phase 3 such as a CMV vaccine, RSV, seasonal influenza. Current mRNA cancer vaccines development, including brain, breast, melanoma, esophagus, lung, ovarian, prostate and solid tumors. Most are aimed for personalized therapy. By 2023, at least 1 viral mRNA vaccine may get approval, whereas a cancer vaccine might take much longer time. Nevertheless, the remaining challenge at the global level is how to truly overcome the vaccine inequity issues in a sustainable way.Copyright © 2023
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Background: Currently five SARS-CoV-2 vaccines are approved in North America (FDA) and Europe (EMA). Across the world other vaccines have been developed but not approved in high-income countries. Of the approved vaccines, 2 are mRNA vaccines, 2 are viral vectored vaccines, and 1 is a protein subunit vaccine. As immunogenicity markers are increasingly being used by regulatory agencies as surrogate markers for vaccine efficacy to inform authorization decisions, this meta-analysis compared the size of immunogenicity responses response elicited by the different COVID-19 vaccine types (mRNA, protein subunit, inactivated virus, viral vectors) and approved and unapproved COVID-19 vaccines. Method(s): Systematic review of trial registers and databases identified RCTs for SARS-CoV-2 vaccines. Risk of bias analysis was conducted using the Cochrane Risk of Bias tool. High risk of bias studies were excluded from analysis. Meta-analysis of seroconversion rates and geometric antibody titers (GMT) for neutralising (NAb) and anti-spike antibodies was conducted, each compared with a placebo using random effects model Cochrane-Mantel Haenszel Tests. Result(s): All studies assessed immunogenicity of COVID-19 vaccines on healthy non-immunocompromised adults between the age of 18 and 59. Statistically significant difference was identified between the different vaccine types for NAb GMT, anti-spike GMT, NAb seroconversion, and anti-spike seroconversion (P< 0.00001 for all). Conversely, no statistical significant difference was identified between approved and unapproved vaccines for NAb seroconversion (P=0.39), Nab GMT (P=0.36), anti-spike seroconversion (P=0.07), and antispike GMT (P=0.54). mRNA vaccines had the best immunogenicity results for NAb seroconversion, GMT, and anti-spike seroconversion. Viral vector vaccines had the lowest results for NAb seroconversion and GMT, while inactivated viruses had the lowest result for anti-spike seroconversion and mRNA vaccines for anti-spike GMT. High heterogeneity was observed across the different studies. Conclusion(s): This metanalysis of 35 randomised trials in 33,813 participants showed approved and unapproved vaccines to be comparable in postvaccination GMT values and seroconversion for both NAb and anti-spike. However, while comparing COVID-19 vaccines by vaccine types, statistically significant differences are observed. Variations in study designs, populations enrolled, and infection prevalence during trial duration could have influenced results.
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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.
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Introduction: Being at high-risk for COVID-19, healthcare workers (HCW) were prioritized in the beginning of vaccination campaigns in Tunisia. The emergence of several variants raises the issue of resistance and postvaccination infection. Aim(s): To study epidemiological and clinical characteristics of COVID-19 infection in HCW who previously had COVID19 vaccine. Method(s): Retrospective descriptive study focusing on Rabta hospital's HCW who presented themselves for a reinstatement visit after post-vaccination COVID-19 infection, from 15 March to 31 December 2021. Result(s): There were 122 HCW with a mean age of 42.8 years, a sex ratio of 0.5, and an average professional seniority of 13.8 years. 32% worked full-time in COVID-19 wards and13.1% had a history of COVID-19 before vaccination. Half had received two doses of vaccine. They were vaccinated mainly with mRNA (66.4%), viral vector (19.9%) or attenuated virus (12.3%). Symptoms appeared, on average, 35 days after the last dose of vaccine and the disease was confirmed by RT-PCR after 3 days of the symptom's onset. The main symptoms described were asthenia (66.4%), cough (66.4%), headache (62.3%), anosmia (64.8%), ageusia (55.7%), fever (52.2%), diarrhea (40.2%) ans dyspnea (21.3%). They were mainly put on symptomatic treatment and home rest for 11 days. However, 15% had an extension of their sick-leave and 2.5% presented a severe form requiring hospitalization. On return to work, 59.8% reported the persistence of symptoms including cough (18.9%), asthenia (11.5%), dyspnea (9.8%), anosmia and ageusia (7.4%). Conclusion(s): Vaccinated HCW presented mainly a mild form of COVID-19. Vaccination is an important and promising means to end this pandemic.
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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 vaccines)have 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.
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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 vaccines)have 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.
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Background COVID19 has emerged in the last 3 years thus different types of vaccines are massively administered globally which exhibit systemic and cardiac side effects mostly myocarditis and pericarditis. We present a case of a 29 YO completely healthy male, non-smoker with negative FHX of cardiac diseases, who developed acute pericarditis after the first dose of the "viral-vector" vaccine and evolved rapidly into constrictive pericarditis in 3 weeks duration. The patient started to complain of dyspnea III-IV and central chest pain relieved by bending forward day 3 post-vaccine, labeled at EMD with acute pericarditis. NSAID and colchicine were started & by 3rd-week outpatient follow-up. Despite a full adequate medx course, we found him to have persistent Dyspnea NYHA II with evidence of constrictive pericarditis on echocardiography, cCT and cMRI after 1 month. He refused myocardial biopsy. Methods we used the serial TTE studies showed small pericardial effusion <1cm and then signs of septal bounce, tran MV/TV respiratory variation and thickned pericardium, same features seen on cCT scan. In addition to a positive LGE on cMRI with 18 months follow-up. Results post vaccine constrictive pericarditis is not uncommon, early detection and appropriate management is the mainstay to avoid unwanted consequences. Conclusion Although there are many reports and registries of post-vaccine myo/pericarditis, the exact association is still unclear and requires further investigation. [Formula presented]Copyright © 2023 American College of Cardiology Foundation
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A plant-based heterologous expression system is an attractive option for recombinant protein production because it is based on a eukaryotic system of high feasibility, and low biological risks. Frequently, binary vector systems are used for transient gene-expression in plants. However, plant virus vector-based systems offer advantages for higher protein yields due to their self-replicating machinery. In the present study, we show an efficient protocol using a plant virus vector based on a tobravirus, pepper ringspot virus, that was employed for transient expression of severe acute respiratory syndrome coronavirus 2 partial gene fragments of the spike (named S1-N) and the nucleocapsid (named N) proteins in Nicotiana benthamiana plants. Purified proteins yield of 40-60 µg/g of fresh leaves were obtained. Both proteins, S1-N and N, showed high and specific reactivities against convalescent patients' sera by the enzyme-linked immunosorbent assay format. The advantages and critical points in using this plant virus vector are discussed.
Subject(s)
COVID-19 , RNA Viruses , Humans , SARS-CoV-2/genetics , Recombinant Proteins , Enzyme-Linked Immunosorbent Assay , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
Since SARS-CoV-2 was identified, the scientific community has tried to understand the variables that can influence its spread. Several studies have already highlighted a possible link between particulate matter (PM) and COVID-19. This work is a brief discussion about the latest findings on this topic, highlighting the gaps in the current results and possible tips for future studies. Based on the literature outcomes, PM is suspected to play a double role in COVID-19: a chronic and an acute one. The chronic role is related to the possible influence of long-term and short-term exposure to high concentrations of PM in developing severe forms of COVID-19, including death. The acute role is linked to the possible carrier function of PM in SARS-CoV-2. The scientific community seems sure that the inflammatory effect on the respiratory system of short-term exposure to a high concentration of PM, and other additional negative effects on human health in cases of longer exposure, increases the risk of developing a more severe form of COVID-19 in cases of contagion. On the contrary, the results regarding PM acting as a carrier of SARS-CoV-2 are more conflicting, especially regarding the possible inactivation of the virus in the environment, and no final explanation on the possible acute role of PM in the spread of COVID-19 can be inferred.
Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , Particulate Matter/analysis , SARS-CoV-2 , Air Pollutants/toxicity , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysisABSTRACT
Background: Amyopathic dermatomyositis is a rare autoimmune skin disease with similar cutaneous manifestations as classic dermatomyositis (CDM), but with absent or subclinical muscle involvement i.e. Clinically Amyopathic Dermatomyositis (CADM). Inciting agents including vaccines have been linked to CADM. We describe a case of new-onset CADM associated with COVID-19 vaccine. Objective(s): To illustrate the occurrence of new-onset CADM in a 27-year- old male following COVID-19 immunization. Case Summary: A previously well 27-year- old male developed joint and muscle aches accompanied by scattered erythematous patches on the face and both upper and lower extremities, a week after receiving first dose of viral vector SARS-CoV- 2 vaccine. He took an anti-histamine and paracetamol with some relief of pains and slight clearing of the rashes. He proceeded to receive a second dose of the same vaccine 2 months later. A few days following the second dose, there was exacerbation of the skin lesions and was referred to Rheumatology clinics. Physical exam disclosed an ambulatory well-built male with normal vital signs and no objective muscle weakness. Skin involvement included facial rash, and the characteristic Heliotrope rash, Gottron's papules, and Holster sign. Complete blood counts, chemistries and muscle enzymes were within normal. Antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR) and Smith/ribonucleoprotein (Sm/RNP) antibody were positive. He was managed with tapering prednisone and maintained on methotrexate and folic acid with significant improvement at time of this report. Conclusion(s): This is the first reported case of adverse reaction to COVID-19 vaccine that had studied in detail the skin and systemic autoimmune reaction. Development of autoimmune reaction following SARS-CoV- 2 vaccine has been described extensively;however, evidence of autoimmunity following vaccination is still relatively scant. Our case suggests that in predisposed subjects' vaccination could trigger an autoimmune reaction similar to the natural infection.
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Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.
Subject(s)
COVID-19 , Viral Vaccines , Humans , Animals , Mice , Antibodies, Neutralizing , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Measles virus/genetics , Antibodies, Viral , COVID-19/prevention & control , Measles VaccineABSTRACT
With the continuation of the coronavirus disease 2019 pandemic and the emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, the control of the spread of the virus remains urgent. Various animals, including cats, ferrets, hamsters, nonhuman primates, minks, tree shrews, fruit bats, and rabbits, are susceptible to SARS-CoV-2 infection naturally or experimentally. Therefore, to avoid animals from becoming mixing vessels of the virus, vaccination of animals should be considered. In the present study, we report the establishment of an efficient and stable system using Newcastle disease virus (NDV) as a vector to express SARS-CoV-2 spike protein/subunit for the rapid generation of vaccines against SARS-CoV-2 in animals. Our data showed that the S and S1 protein was sufficiently expressed in rNDV-S and rNDV-S1-infected cells, respectively. The S protein was incorporated into and displayed on the surface of rNDV-S viral particles. Intramuscular immunization with rNDV-S was found to induce the highest level of binding and neutralizing antibodies, as well as strong S-specific T-cell response in mice. Intranasal immunization with rNDV-S1 provoked a robust T-cell response but barely any detectable antibodies. Overall, the NDV-vectored vaccine candidates were able to induce profound humoral and cellular immunity, which will provide a good system for developing vaccines targeting both T-cell and antibody responses.
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Purpose: Most developing countries do not have access to high-efficiency mRNA vaccine. In Thailand, the first and most available vaccines were inactivated, and later on, viral vector vaccine. Here, we reported the efficacy of inactivated and viral vector vaccine in preventing severe disease and death in kidney transplant recipients. Method(s): This is a retrospective study comprised 45 kidney transplant recipients with Covid-19 infection. Patients were classified into 2 groups based on vaccination status before COVID-19 infection. Patients in group 1 were vaccinated with either inactivated or viral vector vaccine and patients in group 2 were unvaccinated. Group 1 was also subdivided into fully and partially vaccinated. All patients received the same standard of care. Outcomes of interest were rate of death, pneumonia and requirement of oxygen therapy. Result(s): There were 23 patients (51%) in group 1 [7 fully vaccinated (5 inactivated, 2 viral vector), 16 partially vaccinated (all viral vector)] and 22 patients (49%) in group 2. All of baseline characteristics including recipient factors, donor factors, immunologic factors and immunosuppressive regimens were similar between groups except only mean recipient age was older in group 1 (55 +/- 11 years in group 1 VS 48 +/- 15 years in group 2, p = 0.035). Of 45 patients in this study, 11 patients died (24%). Significantly more death occurred in group 2. Three patients (all partially vaccinated) and 8 patients died in group 1 and group 2 respectively (13% VS 36%, p = 0.03). No patient receiving full vaccination died. Pneumonia developed equally in both groups (70% VS 71%, p = 0.89). There was a trend toward less oxygen requirement in group 1 (50% VS 74% p = 0.10) as well as less ventilator requirement (9% VS 19% p = 0.48). Conclusion(s): Inactivated and viral vector COVID-19 vaccines have good efficacy in mortality reduction in kidney transplant recipients. Even partial vaccination can exert some protection against death. However, to achieve better prevention, full vaccination should be encouraged to all kidney transplant recipients.
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Purpose: Recent data has shown poor antibody response to SARS-CoV-2 vaccination among adult kidney transplant (tx) recipients, with seroconversion ranging between 22%-58% after two mRNA vaccine doses. Here, we evaluated the antibody and T cell response to SARS-CoV-2 vaccination and evaluate the effects of intensified immunosuppression on such response in pediatric (ped) kidney tx recipients. Method(s): Between April and November 2021, 31 ped renal tx patients (pts)aged 13-22 years old had SARS-CoV-2 spike IgG assessment after receiving 2 doses of SARS-CoV-2 mRNA or 1 dose of viral vector vaccine. Pts were evaluated by their level of immunosuppression: A) standard immunosuppression (tacrolimus, mycophenolate mofetil +/- steroids) or B) intensified immunosuppression (standard immunosuppression + solumedrol pulse, IVIG, rituximab, and/or tocilizumab within 11 months prior to and up to 5 months after SARS-CoV-2 vaccination). A subgroup of 18 pts had SARS-CoV-2 Tc assessment post-vaccination. Result(s): 23 of 31 (74.2%) pts seroconverted at a median assessment time of 83 days (IQR 43-124) post-vaccination. There was no difference in the use of steroid-based or steroid-free immunosuppression between the two groups or the type of vaccine received (Table 1). 15 of 17 (88.2%) of those who received standard immunosuppression seroconverted post-vaccination compared to 8 of 14 (57.1%) in those who received intensified immunosuppression (Table 1;p = 0.10). In a subgroup of pts who had SARS-CoV-2 spike-specific Tc testing, 7 of 7 (100%) in the standard immunosuppression group had positive Tc compared to 7 of 11 (63.6%) in the intensified immunosuppression group (Table 1, p = 0.12). There was no leukopenia or difference in the WBC count in either group at the time of Tc testing (Table 1;p = 0.97). No pts developed symptomatic SARS-CoV-2 infection. Conclusion(s): Ped renal tx recipients appear to have higher rates of seroconversion after the standard 2-dose mRNA or 1-dose viral vector SARS-CoV-2 vaccination compared to adult renal tx recipients. The intensified immunosuppression group appears to have a trend towards lower SARS-CoV-2 spike IgG and Tc conversion, however, results are limited by the small sample size. Larger studies are needed to better understand the humoral and cellular response to SARS-CoV-2 vaccination in this group. (Figure Presented).
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Purpose/Objectives: The delivery of nucleic acids to cells has revolutionized medicine and enabled new technologies such as mRNA vaccines and stem cell therapies. These recent advances rely on delivery vehicles to stabilize the genetic payload and increase cellular transfection. While engineered viruses are efficient vectors for ex vivo cellular reprogramming, they are not ideal for in vivo gene therapies as repeated dosing leads to anti-vector immunity. Lipid nanoparticles have thus emerged as the best alternative to viral vectors for in vivo nucleic acid delivery. However, all FDA-approved lipid nanoparticles have been linked to inflammatory responses, undesirable for regenerative medicine applications that require precise immunomodulation. Thus, non-immunogenic delivery materials must be developed to fulfill the immense potential of gene therapy in regenerative medicine. Lipid nanoparticles typically comprise 4 different lipids, with the ionizable amino lipid being the main driver of potency and immunogenicity. A way to reduce immunogenicity is to develop lipid nanoparticles that minimize the amount of lipids per gram of nucleic acids. To do so, we developed a novel class of ionizable amino lipids with high charge density. Our primary objective is to design a lipid nanoparticle that maximizes RNA delivery and minimizes immunogenicity. Methodology: We designed a library of proprietary ionizable lipids based on the structure of a poly(amido amine) dendron. The structure is modular, which allowed us to systematically vary molecular motifs to optimize important physiochemical parameters: Lipid-to-RNA ratio;apparent pKa;surface zeta potential;size distribution;and RNA encapsulation These structures are also designed to include a higher number of amines compared to current ionizable lipids. This improves ionization charge density of the lipid and lowers the amount of lipid required to encapsulate RNA. In this study, lipid nanoparticles contain an ionizable lipid selected from our library, cholesterol, a phospholipid, and a PEG-lipid. The lipids and formulation conditions were selected to mimic Moderna's COVID-19 vaccine (SpikeVax), albeit with different lipid-to-RNA ratios. C57BL/6 mice were injected intramuscularly with nanoparticles co-formulated with a firefly luciferase mRNA and ovalbumin mRNA to simultaneously study transfection efficiency and antigen-specific immune responses. Nanoparticles that comprise SM-102, the ionizable lipid used in SpikeVax, were used as a comparative control due to their high potency and immunogenicity. Luciferase activity was detected using an IVIS Spectrum, and key organs were harvested for immune phenotyping. Results: We have so far determined the effect of hydrophobic motifs on apparent pKa and RNA encapsulation. Our best lipids with optimized tails did not induce IFN-I responses in vitro and demonstrated comparable in vivo efficacy to SM-102. We are currently in the process of collecting immunogenicity data which we expect to complete prior to the conference. Conclusion/Significance: We have produced a novel set of lipid nanoparticles that efficiently transfect cells in vivo. These new particles deliver RNA with half of the lipid mass used in SpikeVax, which can reduce the amount of material-induced immunogenicity. This result opens the door to developing mRNA vaccines with fewer side effects and equitable gene therapies for untreatable diseases such as inflammatory and autoimmune disorders.
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Background: Vaccinations against SARS-CoV-2 represent a fundamental tool in controlling the pandemic. To date, data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis, are limited. Objectives: In this study we aimed at evaluating the safety of anti-SARS-CoV-2 vaccines in a multicentric cohort of patients with systemic vasculitis. Methods: Patients with systemic vasculitis from two Rheumatology centres who had received anti-SARS-CoV-2 vaccine were retrospectively examined. The primary outcome was to evaluate, in this multi-centric cohort, the occurence of a disease fare after the administration of the vaccine, defned as development of clinical manifestations related to vasculitis with a concomitant increase in serum infammatory markers. As a secondary outcome we aimed at evaluating, in a monocentric cohort of patients with vasculitis, the occurrence of adverse events (AEs) following vaccine administration compared to healthy controls (HC). Results: We examined 111 patients with systemic vasculitis (n=69 female, n=42 male), with a mean age of 64.3 (± 13) years. Sixty had ANCA-associated vas-culitis (AAV), fourty-two had Giant-Cell Arterities (GCA), five had Periarteritis Nodosa, four had Takayasu's arteritis. One-hundred and five patients received a mRNA vaccine and six a viral vector one. A disease fare occurred in only 2 patients (1.8%) after the frst dose of a mRNA vaccine: both had AAV (microscopic poliangioitis) and developed a pulmunary disease fare (respiratory failure requiring hospitalization and treatment with high-dose glucocorticoids). Of note, one of these patients had multiple previous comorbidities, including a severe COPD. Multivaried analysis, adjusted for age and sex, performed in a single monocentric cohort of patients with systemic vasculitis [n=60 (39 AAV, 21 GCA), 37 female, 23 male, mean age 71 (± 12.5) years] demonstrated a statistically sig-nifcant higher frequency of AEs in vasculitis patients compared to HC (p=0.015) after the frst dose of vaccination. No signifcant differences in the frequency of AEs in vasculitis patients compared to HC after the second dose were detected. All the AEs were mild in both groups (malaise was the most frequently reported);no serious AEs were reported. Conclusion: Our data show a very low incidence of disease fares after the administration of anti-SARS-CoV-2 vaccines in patients with systemic vasculitis. Patients with systemic vasculitis seem more prone to develop mild AEs after the frst dose of the vaccine. Taken together, this data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.