Current vaccine platforms in clinical trials*

Current vaccine platforms in clinical trials*

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The Coronavirus disease-19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2), has impacted human lives in the most profound ways with millions of infections and deaths. Scientists and pharmaceutical companies have been in race to produce vaccines against SARS-CoV-2. Vaccine generation usually demands years...

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... was also documented that two of 42 anti-MERS mRNA vaccine candidates were developed and tested at the pre-clinical stage, but neither proceeded to a large-scale clinical trial to be a licensed vaccine [22]. Currently, 63 anti-SARS-CoV-2 candidate vaccines have been being tested on clinical trials (Table 1). Although mRNA vaccines represent only 11% of all the vaccines developed on various platforms, two mRNA vaccines, mRNA-1273 (developed by Moderna) and BNT162b (developed by Pfizer and BioNTech Ltd.) were the first vaccines approved for emergency use in many countries. ...

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Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 spread globally and creates an alarming situation. Following the SARS-CoV-2 paradigm, therapeutic efficacy is achieved via repurposing several antiviral, antibacterial, and antimalarial drugs. Innate and adaptive immune cells work close to comba...

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... Some of these viruses themselves can cause myocarditis [99]. In this regard, as reported in an exhaustive review about the molecular effects of mRNA vaccines, the type of base substitutions in the liposome-inoculated mRNA [100] could play a role in depressing the normal immune responses. Indeed, mRNA pharmacological interventions for other conditions in which N-methyl pseudouridine (the same base substitution present in the COVID-19 mRNA vaccines) was present have been proposed to suppress or attenuate immunity [100][101][102]. ...
... In this regard, as reported in an exhaustive review about the molecular effects of mRNA vaccines, the type of base substitutions in the liposome-inoculated mRNA [100] could play a role in depressing the normal immune responses. Indeed, mRNA pharmacological interventions for other conditions in which N-methyl pseudouridine (the same base substitution present in the COVID-19 mRNA vaccines) was present have been proposed to suppress or attenuate immunity [100][101][102]. The effect is likely due to the induction of regulatory mechanisms that dampened Type I Interferon production and was highly favored by the type of modified mRNA used. ...
... At the beginning of the COVID-19 immunization campaign, many mass media and organs of health services all over the world repeated that the inoculated material would remain in the deltoid muscle, and only for a few days. The perception by the public was that the mRNA is quickly degraded, which does not apply to the modified mRNA used in the COVID-19 vaccines [100,103,106]. Bio-distribution studies, such as in ref. [103], on liposome micro-particles (LNPs) showed that the material does not stop at the inoculation site. ...
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The coronavirus disease 2019 (COVID-19) has been a challenge for the whole world since the beginning of 2020, and COVID-19 vaccines were considered crucial for disease eradication. Instead of producing classic vaccines, some companies pointed to develop products that mainly function by inducing, into the host, the production of the antigenic protein of SARS-CoV-2 called Spike, injecting an instruction based on RNA or a DNA sequence. Here, we aim to give an overview of the safety profile and the actual known adverse effects of these products in relationship with their mechanism of action. We discuss the use and safety of these products in at-risk people, especially those with autoimmune diseases or with previously reported myocarditis, but also in the general population. We debate the real necessity of administering these products with unclear long-term effects to at-risk people with autoimmune conditions, as well as to healthy people, at the time of omicron variants. This, considering the existence of therapeutic interventions, much more clearly assessed at present compared to the past, and the relatively lower aggressive nature of the new viral variants.
... It stimulates a natural immune response, which depends on T cells and the production of neutralizing antibodies. Thus, in contrast to conventional vaccines, an mRNA vaccine does not contain any viral proteins itself, but only the information that our own cells need to produce a virus trait that triggers the desired immune response (Fig. 1) [2]. ...
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Background COVID-19 vaccination of the population has a great importance, especially in oncological patients. The high incidence of vaccine-associated hypermetabolic lymphadenopathy (VAHL) makes a difficulty in the diagnosis of PET-CT of oncological patients. They should be vaccinated in the side opposite to the expected malignant LNs to avoid unnecessary biopsy and change in therapy. The aim of this study was to assess the role of PET-CT in detection of VAHL after the 2nd dose of Pfizer-BioNTech vaccine in lymphoma patients and compare the incidence of VAHL among lymphoma patients treated with B cell depletion therapy during the 6 months prior to vaccination and those treated > 6 months before vaccination. Results This study comprised 120 lymphoma patients, referred for FDG PET/CT 1–3 weeks after the 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Hypermetabolic LNs were identified in 55%. The incidence of VAHL in lymphoma patients treated with anti-CD20 antibody rituximab during the 6 months prior to vaccination (9%) was significantly lower compared with other lymphoma patients treated with anti-CD20 antibody rituximab > 6 months before vaccination (91%). The incidence and grades of VAHL are significantly high within the 1st week after the 2nd dose of Pfizer-BioNTech vaccine in patients younger than 60 years of age. Only 7 of 37 patients with negative serology had VAHL on PET-CT, whereas 10 of 26 patients with decreased anti-spike titers and 49 of 57 patients with increased anti-spike titers had VAHL on PET-CT. Conclusions VAHL makes challenges in the interpretation of FDG PET/CT in oncology patients. Accurate data collection, regarding the time and site of COVID vaccination, is important to help radiologists in identifying the cause of abnormal nodal FDG uptake. We suggest to schedule FDG PET-CT for lymphoma patients at least 3 weeks after the 2nd dose of Pfizer-BioNTech vaccine.
... By now the available oligonucleotide pharmaceutical products can be classified as antisense oligonucleotides (ASOs) [3], silencing RNAs (siRNAs) [4], aptamers [5] and many more. Since the COVID-19 pandemic, mRNA vaccines and treatments have also gained popularity and have pushed the oligonucleotide field of application even further [6,7]. Advanced drug therapeutics also need advanced analytical methods to ensure the quality of these drugs. ...
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Due to the increasing pharmaceutical interest of oligonucleotides, for example in antisense therapy and vaccines, their analytical characterization is of fundamental importance due to their complex structure. For this purpose, mass spectrometry is a viable tool for structural studies of nucleic acids. Structural information regarding the primary sequence of a nucleic acid can reliably be gained via tandem mass spectrometry (MSMS) fragmentation. In this work, we present the characteristic fragmentation behavior of short-chain oligonucleotides (15–35 nucleotides) with respect to the collision-induced dissociation (CID) voltage used. The relationship and influence of the length of the oligonucleotide and its charge state is also discussed. The results presented here can be helpful for estimating the required fragmentation energies of short-chain oligonucleotides and their sequencing.
... During that period, pharmaceutical companies did not consider mRNA a prospective technology because of doubts about its stability and its low efficacy [101]. Despite mRNA vaccines representing only 11% of all the developed COVID-19 vaccines, two mRNA vaccines, mRNA-1273 and BNT162b, were the first vaccines approved by the FDA and EUA for COVID-19 [102]. Both new mRNA vaccines, BNT162b2, manufactured by Pfizer/BioNTech, and mRNA-1273, produced by Moderna, contain molecules of RNA, modified with pseudo-uridine and encapsulated in a lipid nanoparticle vehicle. ...
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Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two years, many studies have been published suggesting that excessive drinking not only worsens the course of an acute respiratory distress syndrome caused by the SARS-CoV-2 virus but can also exacerbate post-COVID-19 syndrome. Despite all sorts of online speculation, there is no specific scientific data on alcohol-induced complications after vaccination in the literature. Most of the published vaccine clinical trials do not include groups of patients with a history of alcohol-use disorders. This review analyzed the well-known and new mechanisms of action of COVID-19 vaccines on the immune system and the effects of alcohol and its metabolites on these mechanisms.
... RNA therapeutics have recently undergone a historical transition since the U.S. Food and Drug Administration urgently approved mRNA vaccines, enabling a quick response to the coronavirus disease 2019 (COVID-19) pandemic (Hodgson, 2020;Jung and Shin, 2021;Lee and Oh, 2021;Park et al., 2021). The knowledge accumulated in the field of RNA biology was applied when developing COVID-19 mRNA vaccines (Pardi et al., 2018). ...
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RNAs are versatile molecules that are primarily involved in gene regulation and can thus be widely used to advance the fields of therapeutics and diagnostics. In particular, circular RNAs which are highly stable, have emerged as strong candidates for use on next-generation therapeutic platforms. Endogenous circular RNAs control gene regulatory networks by interacting with other biomolecules or through translation into polypeptides. Circular RNAs exhibit cell-type specific expression patterns, which can be altered in tissues and body fluids depending on pathophysiological conditions. Circular RNAs that are aberrantly expressed in diseases can function as biomarkers or therapeutic targets. Moreover, exogenous circular RNAs synthesized in vitro can be introduced into cells as therapeutic molecules to modulate gene expression networks in vivo. Depending on the purpose, synthetic circular RNA sequences can either be identical to endogenous circular RNA sequences or artificially designed. In this review, we introduce the life cycle and known functions of intracellular circular RNAs. The current stage of endogenous circular RNAs as biomarkers and therapeutic targets is also described. Finally, approaches and considerations that are important for applying the available knowledge on endogenous circular RNAs to design exogenous circular RNAs for therapeutic purposes are presented.
... In addition, parasites are able, by damping down and regulating host immunity, to effectively evade the host immune response (14) through a variety of mechanisms, some of which are poorly understood. Current antiparasitic vaccines can be generally categorized into conventional protein-based and gene-based vaccines (15) and vaccines comprising attenuated/irradiation-killed parasites, parasite secretions, or recombinant protein antigens that can activate host protective immune responses (15)(16)(17)(18). ...
... In addition, parasites are able, by damping down and regulating host immunity, to effectively evade the host immune response (14) through a variety of mechanisms, some of which are poorly understood. Current antiparasitic vaccines can be generally categorized into conventional protein-based and gene-based vaccines (15) and vaccines comprising attenuated/irradiation-killed parasites, parasite secretions, or recombinant protein antigens that can activate host protective immune responses (15)(16)(17)(18). ...
... Thus, SAMs require a lower dose of the construct, at least in preclinical models (121,122). This feature of SAM has been evidenced in multiple animal models and humans against a wide variety of infectious diseases, such as those cause by rabies virus, influenza virus, respiratory syncytial virus, HIV, and Ebola virus (15). ...
Article
Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the interplay between parasites and their hosts, and their capacity to escape the host immune system and to regulate host immune responses. For many parasitic diseases, conventional vaccine platforms have generally proven ill suited, considering the complex manufacturing processes involved and the costs they incur, the inability to posttranslationally modify cloned target antigens, and the absence of long-lasting protective immunity induced by these antigens. An effective antiparasite vaccine platform is required to assess the effectiveness of novel vaccine candidates at high throughput. By exploiting the approach that has recently been used successfully to produce highly protective COVID mRNA vaccines, we anticipate a new wave of research to advance the use of mRNA vaccines to prevent parasitic infections in the near future. This article considers the characteristics that are required to develop a potent antiparasite vaccine and provides a conceptual foundation to promote the development of parasite mRNA-based vaccines. We review the recent advances and challenges encountered in developing antiparasite vaccines and evaluate the potential of developing mRNA vaccines against parasites, including those causing diseases such as malaria and schistosomiasis, against which vaccines are currently suboptimal or not yet available.
... Furthermore, Kim et al. (2020) suggested that, apart from the adenovirus type 5-vectored COVID-19 vaccine, clinical research should also focus on the development of dendritic cells (DCs) or artificial APCs-based vaccines via utilizing the lentiviral vector expressing synthetic SARS-CoV-2 protein [109]. Interestingly, it is important to note that mRNA vaccines have several advantages over other vaccines, including the ability to induce T-cell-mediated immune responses, characterized by amounts of IFN-gamma secreted by T cells, as well as antibody-mediated immune responses [105,[110][111][112]. ...
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The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells’ exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly.
... In this sense, based on the above-discussed characteristics of the TcTLE peptide, this sequence is an excellent candidate to be part of a subunit vaccine. Taking into account the experience provided by mRNA or attenuated adenovirus vector vaccines against SARS-CoV-2 and its advantages in the induction and production of immunity, this could be a platform to explore a potential Chagas vaccine (Park et al., 2021). ...
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Trypanosoma cruzi, the causal agent of Chagas disease, has coexisted with humans for thousands of years. Therefore, the parasite has developed several mechanisms of antigenic variability that has allowed it to live inside the cells and evade the host immune response. Since T. cruzi displays an intracellular cycle-stage, our research team focused on providing insights into the CD8+ T cells immune response in chronic Chagas cardiomyopathy. We began our work in the 2000s studying parasite antigens that induce natural immune responses such as the KMP11 protein and TcTLE, its N-terminal derived peptide. Different approaches allowed us to reveal TcTLE peptide as a promiscuous CD8+ T cell epitope, able of inducing multifunctional cellular immune responses and eliciting a humoral response capable of decreasing parasite movement and infective capacity. Next, we demonstrated that as the disease progresses, total CD8+ T cells display a dysfunctional state characterized by a prolonged hyper-activation state along with an increase of inhibitory receptors (2B4, CD160, PD-1, TIM-3, CTLA-4) expression, an increase of specific terminal effector T cells (TTE), a decrease of proliferative capacity, a decrease of stem cell memory (TSCM) frequency, and a decrease of CD28 and CD3ζ expression. Thus, parasite-specific CD8+ T cells undergo clonal exhaustion, distinguished by an increase in late-differentiated cells, a mono-functional response, and enhanced expression of inhibitory receptors. Finally, it was found that anti-parasitic treatment induces an improved CD8+ T cell response in asymptomatic individuals, and a mouse animal model led us to establish a correlation between the quality of the CD8+ T cell responses and the outcome of chronic infection. In the future, using OMICs strategies, the identification of the specific cellular signals involved in disease progression will provide an invaluable resource for discovering new biomarkers of progression or new vaccine and immunotherapy strategies. Also, the inclusion of the TcTLE peptide in the rational design of epitope-based vaccines, the development of immunotherapy strategies using TSCM or the blocking of inhibitory receptors, and the use of the CD8+ T cell response quality to follow treatments, immunotherapies or vaccines, all are alternatives than could be explored in the fight against Chagas disease.
... In silico immune simulation was performed to evaluate the immunogenic potential of our target antigen. The vaccination regime of the only two FDA-approved mRNA-based vaccines developed by Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) has widely been established at day 0 and day 21 or 28, respectively and followed by at least 6 months resting period between the second and the third dose [142][143][144][145][146]. Therefore, we conducted another study according to the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccination regime, where the designed vaccine was administered at 1, 63, 873 time-steps (the first dose was given at time = 0, and each time-step equals to 8 h of real life). ...
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Human polyomavirus type 1, or BK virus (BKV), is a ubiquitous pathogen belonging to the polyomaviridae family mostly known for causing BKV-associated nephropathy (BKVN) and allograft rejection in kidney transplant recipients (KTRs) following the immunosuppression regimens recommended in these patients. Reduction of the immunosuppression level and anti-viral agents are the usual approaches for BKV clearance, which have not met a desired outcome yet. There are also debating matters such as the effect of this pathogen on emerging various comorbidities and the related malignancies in the human population. In this study, a reverse vaccinology approach was implemented to design a mRNA vaccine against BKV by identifying the most antigenic proteins of this pathogen. Potential immunogenic T and B lymphocyte epitopes were predicted through various immunoinformatic tools. The final epitopes were selected according to antigenicity, toxicity, allergenicity, and cytokine inducibility scores. According to the obtained results, the designed vaccine was antigenic, neutral at the physiological pH, non-toxic, and non-allergenic with a world population coverage of 93.77%. Since the mRNA codon optimization ensures the efficient expression of the vaccine in a host cell, evaluation of different parameters showed our designed mRNA vaccine has a stable structure. Moreover, it had strong interactions with toll-like receptor 4 (TLR4) according to the molecular dynamic simulation studies. The in silico immune simulation analyses revealed an overall increase in the immune responses following repeated exposure to the designed vaccine. Based on our findings, the vaccine candidate is ready to be tested as a promising novel mRNA therapeutic vaccine against BKV.
... Instead, let us see how we can make use of omics biotechnologies to better understand the pathology of COVID-19 and other infections, and how vaccines work in order to optimize their efficacy and safety. A new generation of anti-COVID-19 vaccines have been designed according to criteria dictated by genomics and immunomics and make use of recombinant biotechnologies [15,16]. A systems vaccinology approach was used to profile the signature of the immune response to the BNT162b2 mRNA vaccine [17]. ...
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The COVID-19 pandemic had cross-cutting impacts on planetary health, quotidian life, and society. Mass vaccination with the current gene-based vaccines has helped control the pandemic but unfortunately it has not shown effectiveness in preventing the spread of the virus. In addition, not all individuals respond to these vaccines, while others develop adverse reactions that cannot be neglected. It is also a fact that some individuals are more susceptible to infection while others develop effective immunization post-infection. We note here that the person-to-person and population variations in vaccine efficacy and side effects have been studied in the field of vaccinomics long before the COVID-19 pandemic. Additionally, the field of adversomics examines the mechanisms of individual differences in the side effects of health interventions. In this review, we discuss the potential of a multi-omics approach for comprehensive profiling of the benefit/risk ratios of vaccines. Vaccinomics and adversomics stand to benefit planetary health and contribute to the prevention of future pandemics in the 21st century by offering precision guidance to clinical trials as well as promoting precision use of vaccines in ways that proactively respond to individual and population differences in their efficacy and safety. This vision of pandemic prevention based on personalized instead of mass vaccination also calls for equity in access to precision vaccines and diagnostics that support a vision and practice of vaccinomics and adversomics in planetary health.