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1.
Journal of Controlled Release ; 351:215-230, 2022.
Article in English | ScienceDirect | ID: covidwho-2041912

ABSTRACT

Polyethylene glycol (PEG) is a versatile polymer that is widely used as an additive in foods and cosmetics, and as a carrier in PEGylated therapeutics. Even though PEG is thought to be less immunogenic, or perhaps even non-immunogenic, with a variety of physicochemical properties, there is mounting evidence that PEG causes immunogenic responses when conjugated with other materials such as proteins and nanocarriers. Under these conditions, PEG with other materials can result in the production of anti-PEG antibodies after administration. The antibodies that are induced seem to have a deleterious impact on the therapeutic efficacy of subsequently administered PEGylated formulations. In addition, hypersensitivity to PEGylated formulations could be a significant barrier to the utility of PEGylated products. Several reports have linked the presence of anti-PEG antibodies to incidences of complement activation-related pseudoallergy (CARPA) following the administration of PEGylated formulations. The use of COVID-19 mRNA vaccines, which are composed mainly of PEGylated lipid nanoparticles (LNPs), has recently gained wide acceptance, although many cases of post-vaccination hypersensitivity have been documented. Therefore, our review focuses not only on the importance of PEGs and its great role in improving the therapeutic efficacy of various medications, but also on the hypersensitivity reactions attributed to the use of PEGylated products that include PEG-based mRNA COVID-19 vaccines.

2.
International Journal of Molecular Sciences ; 23(18):10881, 2022.
Article in English | ProQuest Central | ID: covidwho-2039874

ABSTRACT

Coronavirus disease-19 (COVID-19) mRNA vaccines are the mainstays of mass vaccination campaigns in most Western countries. However, the emergency conditions in which their development took place made it impossible to fully characterize their effects and mechanism of action. Here, we summarize and discuss available evidence indicating that COVID-19 mRNA vaccines better reflect pharmaceutical drugs than conventional vaccines, as they do not contain antigens but an active SARS-CoV-2 S protein mRNA, representing at the same time an active principle and a prodrug, which upon intracellular translation results in the endogenous production of the SARS-CoV-2 S protein. Both vaccine-derived SARS-CoV-2 S protein mRNA and the resulting S protein exhibit a complex pharmacology and undergo systemic disposition. Defining COVID-19 mRNA vaccines as pharmaceutical drugs has straightforward implications for their pharmacodynamic, pharmacokinetic, clinical and post-marketing safety assessment. Only an accurate characterization of COVID-19 mRNA vaccines as pharmaceutical drugs will guarantee a safe, rational and individualized use of these products.

3.
Canadian Medical Association. Journal ; 194(35), 2022.
Article in English | ProQuest Central | ID: covidwho-2039453

ABSTRACT

Vohra-Miller and Schwartz present several facts about NVX-CoV2373. NVX-CoV2373 (marketed as Nuvaxovid) is a protein-based vaccine against SARS-CoV-2, approved in Canada for adults unable or unwilling to receive an mRNA vaccine. Protein-based vaccines have a long history of use that may make them more acceptable to patients who are hesitant to receive mRNA vaccination. NVX-CoV2373 consists of a recombinant spike protein subunit plus adjuvant. It may also be considered for people who are allergic to components of mRNA vaccines.

4.
Journal of Nanobiotechnology ; 20:1-25, 2022.
Article in English | ProQuest Central | ID: covidwho-2038770

ABSTRACT

The rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.

5.
Vaccinology and Methods in Vaccine Research ; : 201-222, 2022.
Article in English | Scopus | ID: covidwho-2035539

ABSTRACT

The pandemic caused by the novel coronavirus, SARS-CoV-2, first detected in December 2019, resulted in millions of deaths and more than a hundred million confirmed infections in the first 18 months. COVID-19, the disease caused by SARS-CoV-2, is asymptomatic for some, for others it can cause illness ranging from mild flu-like symptoms with the most serious cases manifesting with acute respiratory distress syndrome (ARDS), pneumonia and death. The worldwide effort to develop effective vaccines against COVID-19 and SARS-CoV-2 has been unparalleled throughout history. At the time of writing, there are more than 100 candidate vaccines in clinical development and almost 200 undergoing pre-clinical testing, around the world. These diverse candidates use a range of vaccine strategies and platforms including several relatively novel approaches. Many of these newer strategies have been approved for emergency use and existing data advocate for the critical role that they may have in protecting individuals and reducing the ongoing pandemic. This chapter focusses on nucleic acid and viral vector-based vaccines, currently undergoing post-licensure surveillance, being the most widespread technologies used against the pandemic. As well as reviewing the different vaccine platforms and vaccine candidates, this chapter discusses the events preceding the COVID-19 pandemic that allowed vaccine development to occur at never-before-seen speed, the biological and immunological basis for a SARS-CoV-2 vaccine, the importance of collaborative international efforts and the broad lessons that can be applied towards future pandemics. © 2022 Elsevier Inc. All rights reserved.

6.
BMJ Open ; 12(9):e061752, 2022.
Article in English | MEDLINE | ID: covidwho-2029503

ABSTRACT

OBJECTIVES: While almost 60% of the world has received at least one dose of COVID-19 vaccine, the global distribution of vaccination has not been equitable. Only 4% of the population of low-income countries (LICs) has received a full primary vaccine series, compared with over 70% of the population of high-income nations. DESIGN: We used economic and epidemiological models, parameterised with public data on global vaccination and COVID-19 deaths, to estimate the potential benefits of scaling up vaccination programmes in LICs and lower-middle-income countries (LMICs) in 2022 in the context of global spread of the Omicron variant of SARS-CoV2. SETTING: Low-income and lower-middle-income nations. MAIN OUTCOME MEASURES: Outcomes were expressed as number of avertable deaths through vaccination, costs of scale-up and cost per death averted. We conducted sensitivity analyses over a wide range of parameter estimates to account for uncertainty around key inputs. FINDINGS: Globally, universal vaccination in LIC/LMIC with three doses of an mRNA vaccine would result in an estimated 1.5 million COVID-19 deaths averted with a total estimated cost of US$61 billion and an estimated cost-per-COVID-19 death averted of US$40 800 (sensitivity analysis range: US$7400-US$81 500). Lower estimated infection fatality ratios, higher cost-per-dose and lower vaccine effectiveness or uptake lead to higher cost-per-death averted estimates in the analysis. CONCLUSIONS: Scaling up COVID-19 global vaccination would avert millions of COVID-19 deaths and represents a reasonable investment in the context of the value of a statistical life. Given the magnitude of expected mortality facing LIC/LMIC without vaccination, this effort should be an urgent priority.

7.
Dermatol Ther ; : e15838, 2022.
Article in English | PubMed | ID: covidwho-2029319

ABSTRACT

Urticaria is a disease characterized by wheals and/or angioedema. Chronic spontaneous urticaria (CSU) occurs for longer than 6 weeks and appears independently of any identifiable exogenous stimulus. During the vaccination campaign for Coronavirus disease 2019 (COVID-19) pandemic, several cutaneous adverse events have been described, among which urticaria lasting less than 6 weeks (acute urticaria, AU). AU due to vaccines can be IgE or non-IgE mediated;the former typically develop within 4 hours of drug exposure, the latter occurs later and the mechanism is unclear. In this retrospective study we analyzed the frequency and clinical characteristics of urticaria occurring after COVID-19 vaccine (post-vaccination urticaria relapse, PVUR) in adult CSU patients treated with antihistamine and omalizumab, and in clinical remission.

8.
Case Reports in Ophthalmology ; 13(2):570-577, 2022.
Article in English | ProQuest Central | ID: covidwho-2027127

ABSTRACT

Little is known about the potential ocular adverse events following mRNA-1273 vaccine. We aimed to report a case of multiple evanescent white dot syndrome (MEWDS) developing 3 days following the administration of mRNA-1273 vaccine booster. A 71-year-old white myopic female presented with complaints of seeing “pulsating light” and scotoma with her left eye that started about 3 days following mRNA-1273 vaccine booster administration. The patient was found to have multiple scattered white-yellow outer retinal lesions on dilated fundus exam of the left eye. Visual symptoms and exam findings continued to improve without any intervention confirming a short-lived and self-limiting disease course. Clinical presentation was consistent with a clinical diagnosis of MEWDS. Ophthalmologists need to take detailed vaccination history in patients presenting with MEWDS.

10.
Journal of Visualized Experiments ; 186:17, 2022.
Article in English | MEDLINE | ID: covidwho-2024393

ABSTRACT

In vitro transcribed messenger RNA (mRNA) vaccines have displayed enormous potential in fighting against the coronavirus disease 2019 (COVID-19) pandemic. Efficient and safe delivery systems must be included in the mRNA vaccines due to the fragile properties of mRNA. A self-assembled peptide-poloxamine nanoparticle (PP-sNp) gene delivery system is specifically designed for the pulmonary delivery of nucleic acids and displays promising capabilities in mediating successful mRNA transfection. Here, an improved method for preparing PP-sNp is described to elaborate on how the PP-sNp encapsulates Metridia luciferase (MetLuc) mRNA and successfully transfects cultured cells. MetLuc-mRNA is obtained by an in vitro transcription process from a linear DNA template. A PP-sNp is produced by mixing synthetic peptide/poloxamine with mRNA solution using a microfluidic mixer, allowing for the self-assembly of PP-sNp. The charge of PP-sNp is subsequently evaluated by measuring the zeta potential. Meanwhile, the polydispersity and hydrodynamic size of PP-sNp nanoparticles are measured using dynamic light scattering. The mRNA/PP-sNp nanoparticles are transfected into cultured cells, and supernatants from the cell culture are assayed for luciferase activity. The representative results demonstrate their capacity for in vitro transfection. This protocol may shed light on developing next-generation mRNA vaccine delivery systems.

11.
Vaccines ; 10(8), 2022.
Article in English | Web of Science | ID: covidwho-2024371

ABSTRACT

The COVID-19 mRNA vaccine is one of the most effective strategies used to fight against COVID-19. Recently, venous thromboembolism (VTE) events after COVID-19 mRNA vaccination have been reported in various research. Such a concern may hamper the ongoing COVID-19 vaccination campaign. Based on the US Vaccine Adverse Event Reporting System data, this modified self-controlled case series study investigated the association of COVID-19 mRNA vaccination with VTE events among US adults. We found the VTE incidence rate in the recommended dose interval does not change significantly after receiving COVID-19 mRNA vaccines. This conclusion still holds if the analysis is stratified by age and gender. The VTE onset may not be significantly associated with COVID-19 mRNA vaccination.

12.
Vaccines ; 10(8):1262, 2022.
Article in English | ProQuest Central | ID: covidwho-2024365

ABSTRACT

mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment. Nevertheless, further research is required to optimize RNA stabilization, delivery platforms, and improve clinical efficacy by interacting with the tumor microenvironment to induce a long-term antitumor response. This review provides a comprehensive summary of the available evidence on the recent advances and efforts to overcome existing challenges of mRNA-based treatment strategies, and how these efforts play key roles in offering perceptive insights into future considerations for clinical application.

13.
Vaccines ; 10(8):1209, 2022.
Article in English | ProQuest Central | ID: covidwho-2024330

ABSTRACT

Due to the rapid mutation rate of the virus, a lack of appropriate animal models, insufficient funding, and lack of information regarding the correlates of immune protection, attempts to manufacture a viable vaccine have been largely unsuccessful. While adverse reactions are rare and are usually self-limiting, typically resolving without therapeutic intervention within a few days, physicians’ education on identifying dermatological conditions needs to be improved in order to provide the best care for patients who experience adverse cutaneous reactions. Vectors, including cell-penetrating proteins, lipid carriers, and infected dendritic cells, are currently being studied for their efficacy in clinical trials [21]. Physicians’ education will need to improve to best manage and mitigate possible side effects, and patients will need to be counseled in order to increase confidence in mRNA vaccines.

14.
Journal of Korean Medical Science ; 37(35):e267, 2022.
Article in English | MEDLINE | ID: covidwho-2022641

ABSTRACT

The omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to have high infectivity and is more likely to evade vaccine immunity. However, booster vaccination is expected to strengthen cross-reactive immunity, thereby increasing the vaccine effectiveness (VE). This study aimed to evaluate the relative VE of the 3-dose (booster) vaccination compared with the 2-dose primary series vaccination in healthcare workers during omicron variant-dominant periods. During the omicron-dominant period from February 1, 2022 to February 28, 2022, a 1:1 matched case-control study was conducted. Healthcare workers with positive SARS-CoV-2 test results were classified as positive cases, whereas those with negative results served as controls. Compared with the 2-dose primary series vaccination, booster vaccination with mRNA vaccine showed moderate VE (53.1%). However, in multivariate analysis including the time elapsed after vaccination, the significant VE disappeared, reflecting the impact of recent vaccination rather than the third dose itself.

15.
European Journal of Dermatology ; 32(3):420-421, 2022.
Article in English | MEDLINE | ID: covidwho-2022183
16.
Clin Infect Dis ; 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-2017773

ABSTRACT

Little is known about the decay kinetics of COVID-19 vaccine-elicited SARS-CoV-2 specific T cells. In this study we show a modest decline in the frequency of these T cells at 6 months and demonstrate robust expansion in response to antigen and recognition of spike peptides from the delta variant.

17.
J Biomed Sci ; 29(1):68, 2022.
Article in English | PubMed | ID: covidwho-2021289

ABSTRACT

The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

18.
RMD Open ; 8(2), 2022.
Article in English | ProQuest Central | ID: covidwho-2020256

ABSTRACT

Immunocompromised patients treated with immunosuppressive drugs are at increased risk of adverse outcomes following SARS-CoV-2 infection.1 There is limited information on the effect of immunomodulatory therapies on the quality of SARS-CoV-2 vaccine-induced immunity in these populations.2 In a cohort of patients with immune-mediated inflammatory diseases (IMIDs) not treated with B-cell depleting agents or corticosteroids, we recently demonstrated that antibody levels and T cell responses showed greater waning by 3 months following the second dose of SARS-CoV-2 mRNA vaccine compared with healthy controls, emphasising the need for third doses of the vaccine.3 Here, we investigated immune responses in uninfected patients with IMID following a third dose of the Pfizer/BioNTech BNT162b2 or Moderna mRNA-1273 mRNA vaccine. NS, non-significant;RBD, receptor binding domain;FPR, false positive rate;PBMC, peripheral blood mononuclear cells;DMSO, dimethyl sulfoxide;SQRT, square root. Competing interests VP has no personal financial ties with any pharmaceutical company but has received honoraria for speaker and/or advisory board member roles from AbbVie, Almirall, Celgene, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer, Sanofi, UCB and Union Therapeutics.

19.
Semin Thromb Hemost ; 2022.
Article in English | Web of Science | ID: covidwho-2016942

ABSTRACT

Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We present the result of a signal detection analysis aimed at exploring a possible association between COVID-19 immunization and occurrence of AHA. A disproportionality analysis on the World Health Organization (WHO) database was performed to investigate the presence of a signal of risk for AHA associated with COVID-19 vaccines. Reports of AHA associated with any COVID-19 vaccine included in the WHO database were then integrated with those available on the Food and Drug Administration Vaccine Adverse Events Reporting System and those published in the medical literature. The WHO database included 146 reports of AHA. The information component (IC) was significant for the association of AHA with all COVID-19 vaccines (IC025: 1.1) and with the vaccine product BNT162b2 (IC025: 1.6). After duplicate exclusion, 96 unique cases of AHA following COVID-19 vaccines have been reviewed. Median time to diagnosis was 18 days and 40% of cases documented the occurrence after the second dose. Overall, in 57% of the investigated cases, a preexisting condition predisposing to AHA was excluded. About 22% of cases occurred in subjects with age </=65 years and there was no case associated with pregnancy. Mortality was 11%. Although we cannot exclude that the unexpected frequency of AHA diagnosis can be explained by a detection bias, the signal for COVID-19 vaccine-related AHA is robust and deserves further investigations.

20.
Scientific Reports ; 12(1):14772, 2022.
Article in English | MEDLINE | ID: covidwho-2016839

ABSTRACT

Limited data exists on SARS-CoV-2 sustained-response to vaccine in patients with rheumatic diseases. This study aims to evaluate neutralizing antibodies (nAB) induced by SARS-CoV-2 vaccine after 3 to 6 months from administration in Systemic Lupus Erythematosus (SLE) patients, as a surrogate of sustained-immunological response. This cross-sectional study compared nAB titre of 39 SLE patients and 37 Healthy individuals with no previous SARS-CoV-2 infection, who had all received a complete regimen of a mRNA SARS-CoV-2 vaccine within the last 3 to 6 months. We included four lines of SLE treatment including Not-treated, Hydroxychloroquine, immunosuppressive drugs and biological therapy. Glucocorticoids were allowed in all groups. Healthy and Not-treated individuals showed the highest levels of nAB. Treated patients presented lower nAB titres compared to Healthy: a 73% decrease for First-Line patients, 56% for Second-Line treatment and 72% for Third-Line. A multivariate analysis pointed to Glucocorticoids as the most associated factor with declining nAB levels (75% decrease) in treated SLE. Furthermore, a significant reduction in nAB titres was observed for Rituximab-users compared to Healthy subjects (89% decrease). Medium-term response of SLE patients to SARS-CoV-2 mRNA vaccines is negatively impacted in Glucocorticoids and Rituximab users. These findings might help to inform recommendations in vaccination protocols for SLE patients.

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