Vaccine Concepts Research Articles

MRNA vaccines for infectious diseases - advances, challenges and opportunities.

The concept of mRNA-based vaccines emerged more than three decades ago. Groundbreaking discoveries and technological advancements over the past 20 years have resolved the major roadblocks that initially delayed application of this new vaccine modality. The rapid development of nucleoside-modified COVID-19 mRNA vaccines demonstrated that this immunization platform is easy to develop, has an acceptable safety profile and can be produced at a large scale. The flexibility and ease of antigen design have enabled mRNA vaccines to enter development for a wide range of viruses as well as for various bacteria and parasites. However, gaps in our knowledge limit the development of next-generation mRNA vaccines with increased potency and safety. A deeper understanding of the mechanisms of action of mRNA vaccines, application of novel technologies enabling rational antigen design, andinnovative vaccine delivery strategies and vaccination regimens will likely yield potent novel vaccines against a wide range of pathogens.

Vaccine mandates

In this month's article, George Winter looks at the concept of mandatory vaccination and its role in future pandemics

Addressing Sexually Transmitted Infections Due to Neisseria gonorrhoeae in the Present and Future.

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination

BackgroundClostridium spp. has demonstrated therapeutic potential in cancer treatment through intravenous or intratumoral administration. This approach has expanded to include non-pathogenic clostridia for the treatment of various diseases, underscoring the innovative concept of oral-spore vaccination using clostridia. Recent advancements in the field of synthetic biology have significantly enhanced the development of Clostridium-based bio-therapeutics. These advancements are particularly notable in the areas of efficient protein overexpression and secretion, which are crucial for the feasibility of oral vaccination strategies. Here, we present two examples of genetically engineered Clostridium candidates: one as an oral cancer vaccine and the other as an antiviral oral vaccine against SARS-CoV-2.ResultsUsing five validated promoters and a signal peptide derived from Clostridium sporogenes, a series of full-length NY-ESO-1/CTAG1, a promising cancer vaccine candidate, expression vectors were constructed and transformed into C. sporogenes and Clostridium butyricum. Western blotting analysis confirmed efficient expression and secretion of NY-ESO-1 in clostridia, with specific promoters leading to enhanced detection signals. Additionally, the fusion of a reported bacterial adjuvant to NY-ESO-1 for improved immune recognition led to the cloning difficulties in E. coli. The use of an AUU start codon successfully mitigated potential toxicity issues in E. coli, enabling the secretion of recombinant proteins in C. sporogenes and C. butyricum. We further demonstrate the successful replacement of PyrE loci with high-expression cassettes carrying NY-ESO-1 and adjuvant-fused NY-ESO-1, achieving plasmid-free clostridia capable of secreting the antigens. Lastly, the study successfully extends its multiplex genetic manipulations to engineer clostridia for the secretion of SARS-CoV-2-related Spike_S1 antigens.ConclusionsThis study successfully demonstrated that C. butyricum and C. sporogenes can produce the two recombinant antigen proteins (NY-ESO-1 and SARS-CoV-2-related Spike_S1 antigens) through genetic manipulations, utilizing the AUU start codon. This approach overcomes challenges in cloning difficult proteins in E. coli. These findings underscore the feasibility of harnessing commensal clostridia for antigen protein secretion, emphasizing the applicability of non-canonical translation initiation across diverse species with broad implications for medical or industrial biotechnology.

Periodontal vaccines via plantibodies: Bridging the gap between aspiration and achievement

Periodontitis, a multifaceted immune-inflammatory disorder, is intricately linked to systemic conditions such as cardiovascular disease and diabetes mellitus. Recent advancements in cellular and molecular biology have catalyzed the development of innovative vaccination strategies for various viral diseases. The concept of vaccination, pioneered by Edward Jenner in the late 18th century, capitalizes on the phenomenon of acquired immunity following recovery from an illness. Jenner's groundbreaking work with cowpox virus, which conferred cross-protection against smallpox, laid the foundation for modern vaccination practices.The advent of microbial genome sequencing and bioinformatics has revolutionized our ability to explore the genetic makeup of human pathogens comprehensively. This approach holds promise for identifying novel targets for antimicrobial drugs and vaccines, providing new avenues for combating infectious diseases.Given the pervasive nature of periodontal disease, there is an imperative need for effective management and prevention strategies. In the realm of immunization, the emergence of plant-based vaccines represents a novel paradigm. This review employed various search engines, including PubMed, Embase, Web of Science, Cochrane, Medline, and Google Scholar, to identify pertinent articles in medical and dental research. The findings from these studies underscore the potential efficacy of plant-derived vaccines in addressing a diverse range of disorders, including periodontal disease.This comprehensive review sheds light on the broad spectrum of applications of plant-based vaccines in periodontal care. By harnessing the unique properties of plant-derived antigens, these vaccines hold promise for offering safe, effective, and scalable solutions for the prevention and management of periodontitis. Further research and clinical trials are warranted to explore the full potential of plant-based vaccines in revolutionizing periodontal therapeutics.

Assessment of feasibility of mRNA vaccines for cancer treatment

Cancer is the group of disease that has high morbidity rate, the traditional treatment people keep using have a lot of limitations. Although the concept of mRNA vaccines has just emerged in the 20th century, it has demonstrated its good availability during the COVID-19 pandemic. From this, researchers infer that mRNA also has great application prospects in other areas, and cancer immunotherapy has become one of them. mRNA vaccine used to have low translation efficiency and strong mRNA immunogenicity but recent research about mRNA sequence optimization could overcome most of these problems. But to apply this platform vaccine to target tumour cells specifically, the target chosen is very important and still needs a lot of research about it. This article reviews the current approach to mRNA vaccine and its therapeutic usage for cancer. Based on the current clinical studies, the mRNA vaccine might be a good auxiliary tool for cancer treatment.

Drug resistance and therapeutic advances in Treponema pallidum: A review

Treponema pallidum, a common pathogen in sexually transmitted diseases, has emerged as a significant public health threat in recent decades, showing a gradual increase in global prevalence. Antibiotics have been the primary method to treat Treponema pallidum infections. However, high-dose antibiotic use in clinical trials has raised concerns and unveiled a series of issues. This paper employs a literature review approach to summarize and compare scientific studies conducted in various countries and regions regarding Treponema pallidum in recent years. It aims to introduce and summarize the drug resistance of Treponema pallidum and the current progress in treatment. Studies indicate widespread resistance of Treponema pallidum to macrolides, while no resistance has been found to first-line drugs like benzathine penicillin and other alternative medications. Presently, benzathine penicillin remains pivotal in syphilis treatment. Alternatives such as ceftriaxone, second-generation tetracyclines, amoxicillin, and adjunctive immunomodulators, after clinical trials, have been used in early or late-stage syphilis treatment and prevention. The concept and research direction of syphilis vaccines are emerging and are poised to be a crucial approach in curtailing Treponema pallidum transmission. Diversified drug treatment strategies and the development of syphilis vaccines hold significant implications in safeguarding public health and ensuring global health security.

Abrogation and homeostatic restoration of IgE responses by a universal IgE allergy CTL vaccine-The three signal self/non-self/self (S/NS/S) theory.

Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the CTLs induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE-secreting B cells and plasma cells expressing surface nECP-MHCIa as targets. The study herein has enabled the identification of nECPs, A32 and SP-1/SP-2 nonameric natural peptidesproduced through the correspondence principle. Vaccination using nECP induced nECP-specific CTL that profoundly suppressed human IgE production in vitro as well as chimeric human IgE production in human IgE/HLA-A2.01/HLA-B7.02 triple transgenic rodents. Furthermore, nECP-tetramer-specific CTLs were found to be converted into CD4 Tregs that restored IgE competence via the homeostatic principle, mediatepred by SREBP-1c suppressed DCs. Thus, nECPs showed causal efficacy and safety as UAVs for treating categorically type I hypersensitivity IgE-mediated allergies. The applied vaccination concept presented provides the foundation to unify, integrate through a singular class of tetramer-specific TCR clonotypes for regulaing human IgE production. The three signal theory pertains to mechanisms of three cells underlying central tolerance (S), breaking self tolerance (NS) and regaining peripheral tolerance (S) via homeostasisconcerning nECP as an efficacious and safe UAV to treat type I IgE-mediated hypersensitivity. The three signal theory impirically extended, may be heuritic for immuno-regulation of adaptive immune repertoire in general.

DNA Vaccines: Their Formulations, Engineering and Delivery.

The concept of DNA vaccination was introduced in the early 1990s. Since then, advancements in the augmentation of the immunogenicity of DNA vaccines have brought this technology to the market, especially in veterinary medicine, to prevent many diseases. Along with the successful COVID mRNA vaccines, the first DNA vaccine for human use, the Indian ZyCovD vaccine against SARS-CoV-2, was approved in 2021. In the current review, we first give an overview of the DNA vaccine focusing on the science, including adjuvants and delivery methods. We then cover some of the emerging science in the field of DNA vaccines, notably efforts to optimize delivery systems, better engineer delivery apparatuses, identify optimal delivery sites, personalize cancer immunotherapy through DNA vaccination, enhance adjuvant science through gene adjuvants, enhance off-target and heritable immunity through epigenetic modification, and predict epitopes with bioinformatic approaches. We also discuss the major limitations of DNA vaccines and we aim to address many theoretical concerns.

Cancer vaccines: from an immunology perspective.

The concept of a therapeutic cancer vaccine to activate anti-tumour immunity pre-dates innovations in checkpoint blockade immunotherapies. However, vaccination strategies have yet to show the hoped-for successes in patients, and unanswered questions regarding the underlying immunological mechanisms behind cancer vaccines have hampered translation to clinical practice. Recent advances in our understanding of the potential of tumour mutational burden and neo-antigen-reactive T cells for response to immunotherapy have re-ignited enthusiasm for cancer vaccination strategies, coupled with the development of novel mRNA-based vaccines following successes in prevention of COVID-19. Here we summarise current developments in cancer vaccines and discuss how advances in our comprehension of the cellular interplay in immunotherapy-responsive tumours may inform better design of therapeutic cancer vaccines, with a focus on the role of dendritic cells as the orchestrators of anti-tumour immunity. The increasing number of clinical trials and research being funnelled into cancer vaccines has demonstrated the 'proof-of-principle', supporting the hypothesis that therapeutic vaccines have potential as an immuno-oncology agent. For efficacious and safe cancer vaccines to be developed, better understanding of the underpinning immunological mechanisms is paramount.

Application of Engineered Dendritic Cell Vaccines in Cancer Immunotherapy: Challenges and Opportunities.

The primary objective of this study is to evaluate the effectiveness of cancer vaccines containing genetically modified dendritic cells (DCs) in inducing transformational immune responses. This paper sheds considerable light on DCs' function in advancing treatment techniques. This objective is achieved by thoroughly analyzing the many facets of DCs and their strategic integration into cancer treatment. Due to their role as immune response regulators, DCs can potentially enhance cancer treatment strategies. DCs have the potential to revolutionize immunotherapy, as shown by a comprehensive analysis of their numerous characteristics. The review deftly transitions from examining the fundamentals of preclinical research to delving into the complexities of clinical implementation while acknowledging the inherent challenges in translating DC vaccine concepts into tangible progress. The analysis also emphasizes the potential synergistic outcomes that can be achieved by combining DC vaccines with established pharmaceuticals, thereby emphasizing the importance of employing a holistic approach to enhance treatment efficacy. Despite the existence of transformative opportunities, advancement is hindered by several obstacles. The exhaustive analysis of technical complexities, regulatory dynamics, and upcoming challenges provides valuable insights for overcoming obstacles requiring strategic navigation to incorporate DC vaccines successfully. This document provides a comprehensive analysis of the developments in DC-based immunotherapy, concentrating on its potential to transform cancer therapy radically.

A Vaccine against Cancer: Can There Be a Possible Strategy to Face the Challenge? Possible Targets and Paradoxical Effects.

Is it possible to have an available vaccine that eradicates cancer? Starting from this question, this article tries to verify the state of the art, proposing a different approach to the issue. The variety of cancers and different and often unknown causes of cancer impede, except in some cited cases, the creation of a classical vaccine directed at the causative agent. The efforts of the scientific community are oriented toward stimulating the immune systems of patients, thereby preventing immune evasion, and heightening chemotherapeutic agents effects against cancer. However, the results are not decisive, because without any warning signs, metastasis often occurs. The purpose of this paper is to elaborate on a vaccine that must be administered to a patient in order to prevent metastasis; metastasis is an event that leads to death, and thus, preventing it could transform cancer into a chronic disease. We underline the fact that the field has not been studied in depth, and that the complexity of metastatic processes should not be underestimated. Then, with the aim of identifying the target of a cancer vaccine, we draw attention to the presence of the paradoxical actions of different mechanisms, pathways, molecules, and immune and non-immune cells characteristic of the tumor microenvironment at the primary site and pre-metastatic niche in order to exclude possible vaccine candidates that have opposite effects/behaviors; after a meticulous evaluation, we propose possible targets to develop a metastasis-targeting vaccine. We conclude that a change in the current concept of a cancer vaccine is needed, and the efforts of the scientific community should be redirected toward a metastasis-targeting vaccine, with the increasing hope of eradicating cancer.

Application of Nanomaterials and Biomaterials in Nanovaccinology

Over the years, the concept of vaccination has encountered great evolution. Most vaccines have been formulated in a way that mimics pathogens in order to activate immune cascades. However, vaccine development was never assumed as a simple task and it involves several studies to obtain detailed knowledge about antigen presentation and recognition by immune system. Nanovaccination has been proposed as one of the most successful break throughs and procurements in health promotion and diseases prevention. Nano vaccines can be classified into various groups based on shape, source, sizes, features and structural constriction. Therefore they are assumed to offer more opportunities and novel approaches to scientists and researches and address unmet needs in vaccine developments. Novel technologies in vaccinology mostly focus on safety-immunogenicity improvements, synergistic immunomodulation, in vivo stability, reduced toxicity and efficient delivery of stimulatory cues. Biomaterials and nano vaccines were proved as promising strategies with optimal safety and efficacy through controlling the release site and pattern for better adjustment of dosing and timing of vaccines and immunotherapies. In this review, we have summarized future horizons and cutting-edge advances of biocompatible nano biomaterials-based platforms such as liposomes, nanoparticles, carbon based structures and membrane based vaccines. We also described the remaining challenges, limitations, and possible breakthroughs in nano vaccines’ formulation and biomaterials application in industrial scale.

Preclinical proof of concept of a tetravalent lentiviral T-cell vaccine against dengue viruses.

Dengue virus (DENV) is responsible for approximately 100 million cases of dengue fever annually, including severe forms such as hemorrhagic dengue and dengue shock syndrome. Despite intensive vaccine research and development spanning several decades, a universally accepted and approved vaccine against dengue fever has not yet been developed. The major challenge associated with the development of such a vaccine is that it should induce simultaneous and equal protection against the four DENV serotypes, because past infection with one serotype may greatly increase the severity of secondary infection with a distinct serotype, a phenomenon known as antibody-dependent enhancement (ADE). Using a lentiviral vector platform that is particularly suitable for the induction of cellular immune responses, we designed a tetravalent T-cell vaccine candidate against DENV ("LV-DEN"). This vaccine candidate has a strong CD8+ T-cell immunogenicity against the targeted non-structural DENV proteins, without inducing antibody response against surface antigens. Evaluation of its protective potential in the preclinical flavivirus infection model, i.e., mice knockout for the receptor to the type I IFN, demonstrated its significant protective effect against four distinct DENV serotypes, based on reduced weight loss, viremia, and viral loads in peripheral organs of the challenged mice. These results provide proof of concept for the use of lentiviral vectors for the development of efficient polyvalent T-cell vaccine candidates against all DENV serotypes.

Assessing Brigada Digital de Salud Audience Reach and Engagement: A Digital Community Health Worker Model to Address COVID-19 Misinformation in Spanish on Social Media.

U.S. Spanish-speaking populations experienced gaps in timely COVID-19 information during the pandemic and disproportionate misinformation exposure. Brigada Digital de Salud was established to address these gaps with culturally tailored, Spanish-language COVID-19 information on social media. From 1 May 2021 to 30 April 2023, 495 Twitter, 275 Facebook, and 254 Instagram posts were published and amplified by 10 trained community health workers. A qualitative content analysis was performed to characterize the topics and formats of 251 posts. To assess reach and engagement, page analytics and advertising metrics for 287 posts were examined. Posts predominantly addressed vaccination (49.45%), infection risks (19.12%), and COVID-related scientific concepts (12.84%). Posts were educational (48.14%) and aimed to engage audiences (23.67%), promote resources (12.76%), and debunk misinformation (9.04%). Formats included images/text (55.40%), carousels (27.50%), and videos (17.10%). By 9 June 2023, 394 Facebook, 419 Instagram, and 228 Twitter followers included mainly women ages 24-54. Brigada Digital reached 386,910 people with 552,037 impressions and 96,868 engagements, including 11,292 likes, 15,240 comments/replies, 9718 shares/retweets, and 45,381 video play-throughs. The most engaging posts included videos with audio narration, healthcare providers, influencers, or music artists. This community-based model to engage Spanish-speaking audiences on social media with culturally aligned content to counter misinformation shows promise for addressing public health threats.

A Comprehensive Review on Types of Vaccines: From Classic to Cutting-Edge

Vaccination, one of the most remarkable achievements in the history of medicine, has had a profound impact on public health. Over the centuries, the concept of vaccination has evolved significantly, leading to the development of a diverse array of vaccine types. This abstract provides an overview of the various types of vaccination, from traditional live attenuated vaccines to cutting-edge DNA and mRNA vaccines, highlighting their pros and cons.

Privacy preserving vaccinating‐ and testing‐pass for the European Union

AbstractPhysicians and scientists hope that health‐data will provide new insights into improving medical care and optimizing healthcare costs. However, data protection laws in Europe often place limits on the use of patient data. During the COVID‐19 pandemic, both digital immunity records and data on infections were needed for pandemic management. Using this example, the research project will develop a system concept for vaccination, testing, and recovery proof called privacy preserving pass for vaccination and testing (P3VT), that will make collected data available to research and policy pandemic management in real time and anonymized. P3VT consistently considers the goals of privacy‐by‐design, data minimization and transparency of the EU‐GDPR. Expert interviews validated the system from medical, technical, and privacy perspectives. P3VT offers several advantages compared to the EU digital COVID certificate such as pseudonymized proofing of vaccination, testing, and recovery for a reduction of misuse of sensitive personal data and transparency about the nature, timing, and purpose of the proof. Above that anonymized medical data are provided to improve pandemic management, and research. P3VT is thus an exemplary solution for the comprehensive provision of health‐data for research purposes combined with high‐level data protection. Further areas of application are conceivable.

Immunization and Vaccines

Immunity is the ability of the human body to resist almost all types of organisms and toxins that can damage tissues and organs. The most important is acquired immunity, which develops after exposure to bacteria, viruses, or toxins. Natural immunity consists of protective barriers that prevent the passage of microorganisms such as skin and stomach acid, phagocytosing cells, and the complement system. Vaccines are biological products that protect against a specific disease by stimulating the immune system. This review aims to address the concepts of immunization and vaccination. One of the most basic components of children and adults' right to a healthy life is the protection of them against diseases by vaccination. Immunization services are among the most important public health interventions for children in terms of preventing vaccine-preventable diseases and deaths.

Single shot vaccine for multi-use: An overview

Vaccine research is supported by related fields like microbiology, biochemistry, and immunology. These lead to development of new vaccines for immunization of many diseases. In the pipeline there are more than 500 vaccines which are being extended to some form of peanut allergy, coronary artery diseases, cervical cancer, blindness, gastric ulcers, diabetes etc. New Vaccines against HIV, TB and Malaria are developing by researchers are still under development process because knowledge in some other areas are also important. Many traditional vaccines require multiple injections to provide effective patient protection these lead to costly and inconvenient regimen which gives a idea about single shot vaccines. The single shot vaccines can provide protection with only one injection for curing diseases1. During the development and manufacturing process of single shot vaccines the complex factors must be controlled for a significant influence on efficacy of immune response. Single shot vaccination concept is widely applicable to different types of antigens and vaccines. In future the research is required to know the adjuvants influence and release characteristics in different vaccination regimens.

Synthesis of immunostimulatory saponins: A sweet challenge for carbohydrate chemists

Saponins are a large family of natural glycosides showing a wide range of biological activities. Current research efforts on saponins as vaccine adjuvants have been mainly focused on the development of synthetic analogs. By mimicking the immunomodulatory saponins from Quillaja saponaria (QS), less complex and readily accessible analogs have been synthesized to improve the industrial applicability and efficacy of saponins as vaccine adjuvants. Through the exploration of several structural modifications on the skeleton of QS saponins, including changes in the sugar and aglycone compositions as well as in the nature and configuration of the glycosidic bonds, structure-activity relationship (SAR) studies developed by Pr. Gin in the early 2010s were taken as a starting point for the development of a new generation of immunomodulatory candidates. In this review, the recent synthetic strategies and SAR studies of mono- and bidesmosidic QS saponins are discussed. Original concepts of vaccination including self-adjuvanticity and the development of saponin-based glycoconjugates are described. The synthesis and semi-synthesis of saponin alternatives to QS, such as Momordica saponin and onjisaponin derivatives, are also discussed in this review.