Field Of Vaccinology Research Articles

Adjuvant potential of Peyssonnelia caulifera extract on the efficacy of an influenza vaccine in a murine model

Natural adjuvants have recently garnered interest in the field of vaccinology as their immunostimulatory effects. In this study, we aimed to investigate the potential use of Peyssonnelia caulifera (PC), a marine alga, as a natural adjuvant for an inactivated split A/Puerto Rico/8/1934 H1N1 influenza vaccine (sPR8) in a murine model. We administered PC-adjuvanted vaccines to a murine model via intramuscular prime and boost vaccinations, and subsequently analyzed the induced immunological responses, particularly the production of antigen-specific IgG1 and IgG2a antibodies, memory T and B cell responses, and the protective efficacy against a lethal viral infection. PC extract significantly bolstered the vaccine efficacy, demonstrating balanced Th1/Th2 responses, increased memory T and B cell activities, and improved protection against viral infection. Notably, within 3 days post-vaccination, the PC adjuvant stimulated activation markers on dendritic cells (DCs) and macrophages at the inguinal lymph nodes (ILN), emphasizing its immunostimulatory capabilities. Furthermore, the safety profile of PC was confirmed, showing minimal local inflammation and no significant adverse effects post-vaccination. These findings contribute to our understanding of the immunomodulatory properties of natural adjuvants and suggest the promising roles of natural adjuvants in the development of more effective vaccines for infectious diseases.

Rational Design of Lipid Nanoparticles for Enhanced mRNA Vaccine Delivery via Machine Learning.

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics.

Case-cohort design as an efficient approach to evaluating COVID-19 vaccine effectiveness, waning, heterologous immune effect and optimal dosing interval

Though widely applied in other epidemiological fields, the case-cohort study design has seen little application in the field of vaccinology. Case-cohort studies use probabilistic sampling and reweighting to draw inferences about effects (in this case vaccine efficacy) at the population level in an efficient manner. The SARS-CoV-2 pandemic was met with high vaccine uptake, and high rates of population testing prior to the emergence of Omicron variants of concern, in Ontario, Canada, providing an ideal environment for application of case-cohort methodology. We combined a population-based case line list and vaccination database for the province of Ontario between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2 % sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68 %, 95 % CI 67 %–69 %; second dose efficacy 88 %, 95 % CI 87–88 %). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95 % CI 0.61–0.67) at 6–8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4–6 months after the second vaccine dose, but rose markedly thereafter. We conclude that a case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination in real time, and also served to quantify the timing and magnitude of infection breakthrough risk in the same cohort. Heterologous vaccination and extended dosing intervals improved the durability of immune response.

Deciphering Immune Responses to Immunization via Transcriptional Analysis: A Narrative Review of the Current Evidence towards Personalized Vaccination Strategies.

The development of vaccines has drastically reduced the mortality and morbidity of several diseases. Despite the great success of vaccines, the immunological processes involved in protective immunity are not fully understood and several issues remain to be elucidated. Recently, the advent of high-throughput technologies has enabled a more in-depth investigation of the immune system as a whole and the characterization of the interactions of numerous components of immunity. In the field of vaccinology, these tools allow for the exploration of the molecular mechanisms by which vaccines can induce protective immune responses. In this review, we aim to describe current data on transcriptional responses to vaccination, focusing on similarities and differences of vaccine-induced transcriptional responses among vaccines mostly in healthy adults, but also in high-risk populations, such as the elderly and children. Moreover, the identification of potential predictive biomarkers of vaccine immunogenicity, the effect of age on transcriptional response and future perspectives for the utilization of transcriptomics in the field of vaccinology will be discussed.

Deciphering the Potential of Probiotics in Vaccines.

The demand for vaccines, particularly those prepared from non-conventional sources, is rising due to the emergence of drug resistance around the globe. Probiotic-based vaccines are a wise example of such vaccines which represent new horizons in the field of vaccinology in providing an enhanced and diversified immune response. The justification for incorporating probiotics into vaccines lies in the fact that that they hold the capacity to regulate immune function directly or indirectly by influencing the gastrointestinal microbiota and related pathways. Several animal-model-based studies have also highlighted the efficacy of these vaccines. The aim of this review is to collect and summarize the trends in the recent scientific literature regarding the role of probiotics in vaccines and vaccinology, along with their impact on target populations.

Contralateral versus ipsilateral vaccine boosting for COVID-19: considering the broader scientific landscape.

In the relentless battle against the COVID-19 pandemic, the deployment of mRNA vaccines has stood out as a beacon of hope. The successes of Pfizer-BioNTech NT162b2 and Moderna mRNA-1273 vaccines have been remarkable, marking a revolutionary advancement in the field of vaccinology. Despite their rapid development and impressive efficacy, challenges have emerged, particularly concerning the waning immune response over time and the evolving landscape of SARS-CoV-2 variants. The study published in this issue of JCI by Fazli et al. introduces an approach to potentially enhancing the immune responses generated by COVID-19 mRNA vaccines. The study meticulously examines the outcomes of nearly 1,000 participants who received one or two booster doses with the Pfizer-BioNTech NT162b2 vaccine either ipsilaterally or contralaterally in relation to the initial vaccine dose. Intriguingly, those who received the booster contralaterally exhibited a heightened antibody response that was particularly noteworthy in the later time points after boost.

Advances in Zika virus vaccines and therapeutics: A systematic review

Zika virus (ZIKV) is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide. Its wide transmission route and alarming spread rates are of great concern to the scientific community. Numerous trials have been conducted to develop treatment options for ZIKV infection. This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection. A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development. The results indicate that several therapeutic interventions are being tested against ZIKV infection, such as DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles, and mRNA-based vaccines. In addition, approved anti-ZIKV drugs that can reduce the global burden are discussed. Although many vaccine candidates for ZIKV are at different stages of development, none of them have received Food and Drug Authority approval for use up to now. The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Recent Developments in Layer-by-Layer Assembly for Drug Delivery and Tissue Engineering Applications.

Surfaces with biological functionalities are of great interest for biomaterials, tissue engineering, biophysics, and for controlling biological processes. The layer-by-layer (LbL) assembly is a highly versatile methodology introduced 30 years ago, which consists of assembling complementary polyelectrolytes or biomolecules in a stepwise manner to form thin self-assembled films. In view of its simplicity, compatibility with biological molecules, and adaptability to any kind of supporting material carrier, this technology has undergone major developments over the past decades. Specific applications have emerged in different biomedical fields owing to the possibility to load or immobilize biomolecules with preserved bioactivity, to use an extremely broad range of biomolecules and supporting carriers, and to modify the film's mechanical properties via crosslinking. In this review, the focus is on the recent developments regarding LbL films formed as 2D or 3D objects for applications in drug delivery and tissue engineering. Possible applications in the fields of vaccinology, 3D biomimetic tissue models, as well as bone and cardiovascular tissue engineering are highlighted. In addition, the most recent technological developments in the field of film construction, such as high-content liquid handling or machine learning, which are expected to open new perspectives in the future developments of LbL, are presented.

Generative AI and large language models: A new frontier in reverse vaccinology

Reverse vaccinology is an emerging concept in the field of vaccine development as it facilitates the identification of potential vaccine candidates. Biomedical research has been revolutionized with the recent innovations in Generative Artificial Intelligence (AI) and Large Language Models (LLMs). The intersection of these two technologies is explored in this study. In this study, the impact of Generative AI and LLMs in the field of vaccinology is explored. Through a comprehensive analysis of existing research, prospective use cases, and an experimental case study, this research highlights that LLMs and Generative AI have the potential to enhance the efficiency and accuracy of vaccine candidate identification. This work also discusses the ethical and privacy challenges, such as data consent and potential biases, raised by such applications that require careful consideration. This study paves the way for experts, researchers, and policymakers to further investigate the role and impact of Generative AI and LLM in vaccinology and medicine.

Towards personalized vaccines.

The emergence of vaccinomics and system vaccinology represents a transformative shift in immunization strategies, advocating for personalized vaccines tailored to individual genetic and immunological profiles. Integrating insights from genomics, transcriptomics, proteomics, and immunology, personalized vaccines offer the promise of enhanced efficacy and safety, revolutionizing the field of vaccinology. However, the development of personalized vaccines presents multifaceted challenges, including technical, ethical, economic, and regulatory considerations. Addressing these challenges is essential to ensure equitable access and safety of personalized vaccination strategies. Despite these hurdles, the potential of personalized vaccines to optimize responses and mitigate disease burden underscores the significance of ongoing research and collaboration in advancing precision medicine in immunization.

Global Disparities in COVID-19 Vaccine Distribution: A Call for More Integrated Approaches to Address Inequities in Emerging Health Challenges

The advent of the COVID-19 vaccine signified a historic milestone in the field of vaccinology, showcasing remarkable scientific collaboration and global solidarity. However, the most prominent hurdle in maximizing the global public health impact of vaccines remains the absence of comprehensive and inclusive health systems in both high- and low-resource settings. Our discussion centers around the major contributing factors that played a key role in formulating the rapid and efficacious COVID-19 vaccines. Simultaneously, we illuminate the disparities that have marred the vaccine delivery process throughout the pandemic. In particular, we highlight the case scenarios of two minority and vulnerable communities from the Global South and North—the undocumented migrants in Thailand and the Roma community in Europe—who continue to experience inequitable vaccine access regardless of their location. We note that a crucial programmatic solution that is rooted in inclusive and equitable global public health policy, characterized by empathy and trust and bolstered by digital innovation, is lacking. These examples underscore the significance of establishing a comprehensive and integrated health system at multiple levels across countries and the entire world. Furthermore, we highlight the need for both local and global actors to collaboratively engage in vaccine distribution efforts. By gaining a concise grasp of these intricacies, the global community will be better poised to effectively combat future pandemics and emerging health challenges.

An update on one-dose HPV vaccine studies, immunobridging and humoral immune responses – A meeting report

The 12th HPV Prevention and Control meeting was held on June 2–3, 2022, in Antwerp, Belgium. This technical meeting focused on several topics. This report summarises the discussions and lessons learned on two topics: an update on one-dose HPV vaccination studies and humoral immune responses upon HPV vaccination. Long-term follow-up studies from Costa Rica (eleven years) and India (ten years) report stable levels of antibodies after a single HPV vaccination. High vaccine effectiveness against incident persistent HPV 16/18 infection was seen in India (95.4%, 85.0–99.9) ten years postvaccination and in Kenya (97.5%, 81.7–99.7) eighteen months postvaccination, an important observation in a setting with a higher HPV prevalence. The potential impact of HPV vaccination using a one-dose schedule in India was modelled and showed that implementation of one-dose schedule can contribute towards achieving WHO Cervical Cancer elimination goals. These data support the WHO SAGE recommendations for adopting a one-dose schedule for females aged 9–20 years. Immunobridging studies were discussed during the meeting. General agreement was reached that when thoughtfully applied, they can support and accelerate the expanded use of HPV vaccine with new vaccine schedules, age cohorts, or vaccine formulations. Internationally standardised measurements of HPV immune responses important for the progress of HPV vaccinology field. Humoral immune responses upon HPV vaccination plateau at 24 months regardless of number of doses, therefore, data should be analysed after at least 24 months of follow-up to bridge studies accurately.

Increasing human monoclonal antibody cloning efficiency with a whole-cell modified immunoglobulin-capture assay (mICA).

Expression cloning of fully human monoclonal antibodies (hmAbs) is seeing powerful utility in the field of vaccinology, especially for elucidating vaccine-induced B-cell responses and novel vaccine candidate antigen discovery. Precision of the hmAb cloning process relies on efficient isolation of hmAb-producing plasmablasts of interest. Previously, a novel immunoglobulin-capture assay (ICA) was developed, using single protein vaccine antigens, to enhance the pathogen-specific hmAb cloning output. Here, we report a novel modification of this single-antigen ICA using formalin-treated, fluorescently stained whole cell suspensions of the human bacterial invasive pathogens, Streptococcus pneumoniae and Neisseria meningitidis. Sequestration of IgG secreted by individual vaccine antigen-specific plasmablasts was achieved by the formation of an anti-CD45-streptavidin and biotin anti-IgG scaffold. Suspensions containing heterologous pneumococcal and meningococcal strains were then used to enrich for polysaccharide- and protein antigen-specific plasmablasts, respectively, during single cell sorting. Following application of the modified whole-cell ICA (mICA), ~61% (19/31) of anti-pneumococcal polysaccharide hmAbs were cloned compared to 14% (8/59) obtained using standard (non-mICA) methods - representing a ~4.4-fold increase in hmAb cloning precision. A more modest ~1.7-fold difference was obtained for anti-meningococcal vaccine hmAb cloning; ~88% of hmAbs cloned via mICA versus ~53% cloned via the standard method were specific for a meningococcal surface protein. VDJ sequencing revealed that cloned hmAbs reflected an anamnestic response to both pneumococcal and meningococcal vaccines; diversification within hmAb clones occurred by positive selection for replacement mutations. Thus, we have shown successful utilization of whole bacterial cells in the ICA protocol enabling isolation of hmAbs targeting multiple disparate epitopes, thereby increasing the power of approaches such as reverse vaccinology 2.0 (RV 2.0) for bacterial vaccine antigen discovery.

Evaluation of codon usage patterns and molecular evolution dynamics in Japanese encephalitis virus: An integrated bioinformatics approach.

In the recent survey, Japanese encephalitis (JE) is one of the most common mosquito-borne diseases, accounting for ∼30% of fatalities. The outbreaks of the JE virus (JEV) suggests that exhaustive study is essential for the prevention and management of the disease. The disease mainly spreads in humans and pigs by the vector: mosquito; as this is a major concern, this study had employed various bioinformatics tools to investigate the codon usage bias, evolutionary inference and selection pressure analysis of the Japanese encephalitis virus disease. The results indicated that the JE virus was biased and natural selection was the main factor shaping the codon usage that was determined and confirmed with the Nc, neutrality, PR2 plots and correlation analysis. The evolutionary analysis revealed that the virus had a substitution rate of 1.54×10-4 substitution/site/year and the tMRCA was found to be in 1723. The transmission of the virus in the map found transmissions mostly from China and transmitted across Asia and Africa. The selection pressure analysis employed three methods which had 969th codon site as diversifying site and had many purifying sites that shows the virus had evolved rapidly. The inferences from this study would aid people to employ this methodology on various diseases and also perform insilico studies in the field of vaccinology and immunoinformatics.

MRNA melanoma vaccine revolution spurred by the COVID-19 pandemic.

The advent of mRNA vaccines represents a significant advance in the field of vaccinology. While several vaccine approaches (mRNA, DNA, recombinant protein, and viral-vectored vaccines) had been investigated at the start of the COVID-19 pandemic, mRNA vaccines quickly gained popularity due to superior immunogenicity at a low dose, strong safety/tolerability profiles, and the possibility of rapid vaccine mass manufacturing and deployment to rural regions. In addition to inducing protective neutralizing antibody responses, mRNA vaccines can also elicit high-magnitude cytotoxic T-cell responses comparable to natural viral infections; thereby, drawing significant interest from cancer immunotherapy experts. This mini-review will highlight key developmental milestones and lessons we have learned from mRNA vaccines during the COVID-19 pandemic, with a specific emphasis on clinical trial data gathered so far for mRNA vaccines against melanoma and other forms of cancer.

A Perspective on Current Flavivirus Vaccine Development: A Brief Review.

The flavivirus genus contains several clinically important pathogens that account for tremendous global suffering. Primarily transmitted by mosquitos or ticks, these viruses can cause severe and potentially fatal diseases ranging from hemorrhagic fevers to encephalitis. The extensive global burden is predominantly caused by six flaviviruses: dengue, Zika, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitis. Several vaccines have been developed, and many more are currently being tested in clinical trials. However, flavivirus vaccine development is still confronted with many shortcomings and challenges. With the use of the existing literature, we have studied these hurdles as well as the signs of progress made in flavivirus vaccinology in the context of future development strategies. Moreover, all current licensed and phase-trial flavivirus vaccines have been gathered and discussed based on their vaccine type. Furthermore, potentially relevant vaccine types without any candidates in clinical testing are explored in this review as well. Over the past decades, several modern vaccine types have expanded the field of vaccinology, potentially providing alternative solutions for flavivirus vaccines. These vaccine types offer different development strategies as opposed to traditional vaccines. The included vaccine types were live-attenuated, inactivated, subunit, VLPs, viral vector-based, epitope-based, DNA and mRNA vaccines. Each vaccine type offers different advantages, some more suitable for flaviviruses than others. Additional studies are needed to overcome the barriers currently faced by flavivirus vaccine development, but many potential solutions are currently being explored.

New-age vaccine adjuvants, their development, and future perspective.

In the present scenario, immunization is of utmost importance as it keeps us safe and protects us from infectious agents. Despite the great success in the field of vaccinology, there is a need to not only develop safe and ideal vaccines to fight deadly infections but also improve the quality of existing vaccines in terms of partial or inconsistent protection. Generally, subunit vaccines are known to be safe in nature, but they are mostly found to be incapable of generating the optimum immune response. Hence, there is a great possibility of improving the potential of a vaccine in formulation with novel adjuvants, which can effectively impart superior immunity. The vaccine(s) in formulation with novel adjuvants may also be helpful in fighting pathogens of high antigenic diversity. However, due to the limitations of safety and toxicity, very few human-compatible adjuvants have been approved. In this review, we mainly focus on the need for new and improved vaccines; the definition of and the need for adjuvants; the characteristics and mechanisms of human-compatible adjuvants; the current status of vaccine adjuvants, mucosal vaccine adjuvants, and adjuvants in clinical development; and future directions.

Immunoinformatics and tick vaccinology

Immunoinformatics is an emerging area focused on development and applications of methods used to facilitate vaccine development. There is a growing interest in the field of vaccinology centered on the new omic science named ‘vaccinomics’. However, this approach has not succeeded to provide a solution against major infections affecting both animals and humans, since tick vaccines are still being developed based on conventional biochemical or immunological methods to dissect the molecular structure of the pathogen, looking for a candidate antigen. The availability of complete genomes and the novel advanced technologies, such as data mining, bioinformatics, microarrays, and proteomics, have revolutionized the approach to vaccine development and provided a new impulse to tick research. The aim of this review is to explore how modern vaccinology will contribute to the discovery of new candidate antigens and to understand the research process to improve existing vaccines. Under this concept, the omic age of ticks will make it possible to design vaccines starting from a prediction based on the in silico analysis of gene sequences obtained by data mining using computer algorithms, without the need to keep the pathogen growing in vitro. This new genome-based approach has been named “reverse vaccinology 3.0” or “vaccinomics 1.0” and can be applied to ticks.

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

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

MatchTope: A tool to predict the cross reactivity of peptides complexed with Major Histocompatibility Complex I.

The therapeutic targeting of the immune system, for example in vaccinology and cancer treatment, is a challenging task and the subject of active research. Several in silico tools used for predicting immunogenicity are based on the analysis of peptide sequences binding to the Major Histocompatibility Complex (pMHC). However, few of these bioinformatics tools take into account the pMHC three-dimensional structure. Here, we describe a new bioinformatics tool, MatchTope, developed for predicting peptide similarity, which can trigger cross-reactivity events, by computing and analyzing the electrostatic potentials of pMHC complexes. We validated MatchTope by using previously published data from in vitro assays. We thereby demonstrate the strength of MatchTope for similarity prediction between targets derived from several pathogens as well as for indicating possible cross responses between self and tumor peptides. Our results suggest that MatchTope can enhance and speed up future studies in the fields of vaccinology and cancer immunotherapy.