Development Of Vaccination Strategies Research Articles

Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design.

Gonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria meningitidis induce modest cross-protection against gonococcal infection. However, the presence of proteins in OMVs derived from N. gonorrhoeae that manipulate immune responses could hamper their success as a vaccine. Here we modified two key immunomodulatory proteins of the gonococcus; RmpM, which can elicit 'blocking antibodies', and PorB, an outer membrane porin which contributes to immunosuppression. As meningococcal PorB has adjuvant properties, we replaced gonococcal PorB with a meningococcal PorB. Immunisation with OMVs from N. gonorrhoeae lacking rmpM and expressing meningococcal porB elicited higher antibody titres against model antigens in mice compared to OMVs with native PorB. Further, a gonococcal protein microarray revealed stronger IgG antibody responses to a more diverse range of antigens in the Nm PorB OMV immunised group. Finally, meningococcal PorB OMVs resulted in a Th1-skewed response, exemplified by increased serum IgG2a antibody responses and increased IFNɣ production by splenocytes from immunised mice. In summary, we demonstrate that the replacement of PorB in gonococcal OMVs enhances immune responses and offers a strategy for gonococcal vaccine development.

Combination application of Pickering emulsion and BLS protein nanoparticles enhances vaccine efficacy.

The deficiency of recombinant protein immune response could be compensated for by using nanoparticle platforms or adding immune enhancers, however existing vaccines or adjuvants struggle to elicit durable cellular immune responses. In this work, a protein nanoscaffold, lumazine synthase isolated from Brucella (BLS) was optimally designed that could facilitate cellular uptake of displayed antigens and the maturation of bone marrow-derived dendritic cells (BMDCs), and enhancing humoral immune responses. To enhance cellular immune response, chitosan hydrochloride-stabilized Pickering emulsion (CHSPE) was evaluated as an adjuvant for the BLS nanoscaffold-based vaccine. CHSPE could enhance the recruitment and activation of DCs at the injection site and the uptake of antigen and activation of DCs in the draining lymph nodes (dLNs), compared with commercial adjuvant ISA 206. In addition, CHSPE induced antigen-specific antibody levels comparable to those of ISA 206 and increased the ratio of central memory T cells (TCM) and effector memory T cells (TEM), and promoted the secretion of Th1-type cytokines. Moreover, CHSPE-formulated vaccine provided a similar level of protection to the live attenuated vaccine and was superior to that of ISA 206. Taken together, the combination of the BLS nanoscaffold and CHSPE provides a feasible strategy for recombinant protein subunit vaccine development.

Programmable Macrophage Vesicle Based Bionic Self-Adjuvanting Vaccine for Immunization against Monkeypox Virus.

The emergence of monkeypox has become a global health threat after the COVID-19 pandemic. Due to the lack of available specifically treatment against MPV, developing an available vaccine is thus the most prospective and urgent strategy. Herein, a programmable macrophage vesicle based bionic self-adjuvanting vaccine (AM@AEvs-PB) is first developed for defending against monkeypox virus (MPV). Based on MPV-related antigen-stimulated macrophage-derived vesicles, the nanovaccine is constructed by loading the mature virion (MV)-related intracellular protein (A29L/M1R) and simultaneously modifying with the enveloped virion (EV) antigen (B6R), enabling them to effectively promote antigen presentation and enhance adaptive immune through self-adjuvant strategy. Owing to the synergistic properties of bionic vaccine coloaded MV and EV protein in defensing MPV, the activation ratio of antigen-presenting cells is nearly four times than that of single antigen in the same dose, resulting in stronger immunity in host. Notably, intramuscular injection uptake of AM@AEvs-PB demonstrated vigorous immune-protective effects in the mouse challenge attempt, offering a promising strategy for pre-clinical monkeypox vaccine development.

Prokaryote- and Eukaryote-Based Expression Systems: Advances in Post-Pandemic Viral Antigen Production for Vaccines

This review addresses the ongoing global challenge posed by emerging and evolving viral diseases, underscoring the need for innovative vaccine development strategies. It focuses on the modern approaches to creating vaccines based on recombinant proteins produced in different expression systems, including bacteria, yeast, plants, insects, and mammals. This review analyses the advantages, limitations, and applications of these expression systems for producing vaccine antigens, as well as strategies for designing safer, more effective, and potentially ‘universal’ antigens. The review discusses the development of vaccines for a range of viral diseases, excluding SARS-CoV-2, which has already been extensively studied. The authors present these findings with the aim of contributing to ongoing research and advancing the development of antiviral vaccines.

Developer and Partnership Differences in COVID-19 and Other Infections: Insights from DNA Vaccines

Historically, vaccine development has been heavily supported by government and public institutions. On the other hand, private biopharmaceutical companies have played a significant role in the development of innovative new therapies using novel pharmaceutical technologies. COVID-19 vaccines using new vaccine technologies, such as mRNA and adenoviral vectors, were rapidly developed by emerging biopharmaceutical companies in collaboration with large corporations and public organizations. This underscores the crucial role of emerging biopharma and public–private partnerships in advancing new vaccine technologies. While these innovations have been suggested as models for future vaccines, their applicability to other infectious diseases requires careful assessment. This study investigated the characteristics of the developers and partnerships in the development of DNA vaccines as a next-generation vaccine platform. The analysis revealed that while emerging biopharmaceutical companies and private–private and private–public partnerships were crucial during the COVID-19 pandemic, public organizations and public–public collaborations primarily led to the clinical development of vaccines for other diseases. Strategies for vaccine development using new vaccine technologies should be tailored to the specific characteristics of each disease.

In Silico Development of a Multi-Epitope Subunit Vaccine against Bluetongue Virus in Ovis aries Using Immunoinformatics

The bluetongue virus (BTV), transmitted by biting midges, poses a significant threat to livestock globally. This orbivirus induces bluetongue disease, leading to substantial economic losses in the agricultural sector. The current control measures have limitations, necessitating the development of novel, efficient vaccines. In this study, an immunoinformatics approach is employed to design a multi-epitope subunit vaccine for Ovis aries targeting six BTV serotypes. Focusing on the VP2 capsid protein, the vaccine incorporates B-cell, helper-T lymphocytes (HTL), and cytotoxic T-cell lymphocytes (CTL) epitopes. Molecular docking reveals stable interactions with TLR2 and TLR4 receptors, suggesting the stability of the complex, indicating the potential viability of the multi-epitope vaccine. The computational approach offers a rapid and tailored strategy for vaccine development, highlighting potential efficacy and safety against BTV outbreaks. This work contributes to understanding BTV and presents a promising avenue for effective control.

Influenza A as a True Zoonotic Pathogen: Transmission through Reservoir Hosts

Influenza A virus (IAV) represents a considerable global health threat due to its rapid mutation rates and broad host range, facilitating cross-species transmission and enabling the virus to evade immune defenses. This review explores the molecular mechanisms underlying IAV's pathogenicity, focusing on its zoonotic potential through reservoir hosts, such as wild birds and swine. The virus's ability to undergo antigenic shift and drift allows it to continually adapt to new hosts and environments, posing challenges for control and treatment. Current antiviral therapies are limited by the emergence of resistant strains, underscoring the necessity for innovative vaccine development and treatment strategies. By examining IAV's molecular evolution, immune evasion tactics, and transmission dynamics, this review highlights the critical need for enhanced surveillance, improved therapeutic options, and international cooperation to mitigate future outbreaks. A deeper understanding of these processes is essential to inform public health efforts and combat the persistent threat of IAV.

The Role of Peptides in Combatting HIV Infection: Applications and Insights.

Peptide-based inhibitors represent a promising approach for the treatment of HIV-1, offering a range of potential advantages, including specificity, low toxicity, and the ability to target various stages of the viral lifecycle. This review outlines the current state of research on peptide-based anti-HIV therapies, highlighting key advancements and identifying future research directions. Over the past few years, there has been significant progress in developing synthetic peptide-based drugs that target various stages of the viral life cycle, including entry and replication. These approaches aim to create effective anti-HIV therapies. Additionally, peptides have proven valuable in the development of anti-HIV vaccines. In the quest for effective HIV vaccines, discovering potent antigens and designing suitable vaccine strategies are crucial for overcoming challenges such as low immunogenicity, safety concerns, and increased viral load. Innovative strategies for vaccine development through peptide research are, therefore, a key focus area for achieving effective HIV prevention. This review aims to explore the strategies for designing peptides with anti-HIV activity and to highlight their role in advancing both therapeutic and preventive measures against HIV.

Evaluation of a Low-Temperature Immersion Immunization Strategy for the Infectious Spleen and Kidney Necrosis Virus orf037l Gene-Deleted Attenuated Vaccine

Background: Infectious spleen and kidney necrosis virus (ISKNV) poses a significant threat to aquaculture sustainability, particularly affecting mandarin fish (Siniperca chuatsi) and causing significant economic losses. Methods: To address this challenge, this study developed an ISKNV Δorf037l vaccine strain, where the orf037l gene was knocked out. Infection assays conducted at 28 °C showed that the knocking out the orf037l gene decreased the virulence of ISKNV and reduced lethality against mandarin fish by 26.7% compared to wild-type ISKNV. To further diminish residual virulence, the effect of low-temperature (22 °C) immersion immunization was evaluated. Results: The results indicate that low temperature significantly diminished the virulence of the Δorf037l vaccine strain, elevating the survival rate of mandarin fish to 90%. Furthermore, the vaccine strain effectively triggered the expression of crucial immune-related genes, such as IFN-h, IL-1, IκB, Mx, TNF-α, and Viperin, while inducing the production of specific neutralizing antibodies. Low-temperature immersion with Δorf037l achieved a high relative percentage of survival of 92.6% (n = 30) in mandarin fish, suggesting the potential of Δorf037l as a promising immersion vaccine candidate. Conclusions: These findings contribute to advancing fish immersion vaccine development and demonstrate the importance and broad applicability of temperature optimization strategies in vaccine development. Our work carries profound implications for both the theoretical understanding and practical application in aquaculture disease control.

VIEPred: Predicting Viral Immune Evasion with Multimodal Representation Learning

Abstract Predicting coronaviral immune evasion is crucial for identifying and responding to new COVID-19 variants in advance, thereby optimizing vaccine development and public health strategies to prevent further outbreaks. Hence, we present VIEPred, a model designed to predict mutations in every amino acid of the RBD. However, protein representation learning is a challenge task due to the hierarchical structure of proteins. Our method uses a sequence encoder based on dilated convolutions and attention mechanisms to generate sequence embeddings and a structure encoder employing geometric vector perceptrons (GVP) and graph neural networks (GNN) to produce protein structure representations. These features are combined using a cross-attention fusion module and subsequently processed through a fully connected layer to output the probability of viral immune evasion. Extensive ablation studies led to an optimal model with ACC of 88.4% and AUC of 86.8%. Compared to existing prediction methods, VIEPred demonstrates superior predictive performance across most evaluation metrics for both SARS-CoV-2 and influenza viruses.

COVID-19 from symptoms to prediction: A statistical and machine learning approach

During the COVID-19 pandemic, the analysis of patient data has become a cornerstone for developing effective public health strategies. This study leverages a dataset comprising over 10,000 anonymized patient records from various leading medical institutions to predict COVID-19 patient age groups using a suite of statistical and machine learning techniques. Initially, extensive statistical tests including ANOVA and t-tests were utilized to assess relationships among demographic and symptomatic variables. The study then employed machine learning models such as Decision Tree, Naïve Bayes, KNN, Gradient Boosted Trees, Support Vector Machine, and Random Forest, with rigorous data preprocessing to enhance model accuracy. Further improvements were sought through ensemble methods; bagging, boosting, and stacking. Our findings indicate strong associations between key symptoms and patient age groups, with ensemble methods significantly enhancing model accuracy. Specifically, stacking applied with random forest as a meta leaner exhibited the highest accuracy (0.7054). In addition, the implementation of stacking techniques notably improved the performance of K-Nearest Neighbors (from 0.529 to 0.63) and Naïve Bayes (from 0.554 to 0.622) and demonstrated the most successful prediction method. The study aimed to understand the number of symptoms identified in COVID-19 patients and their association with different age groups. The results can assist doctors and higher authorities in improving treatment strategies. Additionally, several decision-making techniques can be applied during pandemic, tailored to specific age groups, such as resource allocation, medicine availability, vaccine development, and treatment strategies. The integration of these predictive models into clinical settings could support real-time public health responses and targeted intervention strategies.

Navigating the threat of African swine fever: a comprehensive review.

African swine fever (ASF) is caused by Asfivirus and has become one of the most important diseases of swine in recent years. ASF was an endemic disease of the sub-Saharan Africa but later spread to various parts of the world. The infection in ticks and wild swine, alongside global pork trade, drives its spread and persistence. Once introduced to an area, the disease is difficult to eliminate due to sylvatic, domestic, and tick-swine transmission cycles. Because of the existence of various modes of transmission of the ASF virus, biosecurity measures have not been very successful. The line of treatment is not of much use and the outcome of this disease is usually fatal. The prognosis or the recovery of the animal depends on the virulence of the strain involved. Development of vaccines has been attempted but to date has not been very successful. This review focuses on the basic context of ASF, the challenges associated with it, and the options that might be available to prevent its occurrence which includes the different vaccine development strategies tried and tested till now.

Case Studies on Changes and Proposed Process Development Approaches reflecting applicability of PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management.

Vaccines are complex and a very diverse group of products with relatively long product lifecycles. The manufacturing programs for these vaccines need to be continually updated to comply with evolving regulatory expectations. Members of the Parenteral Drug Association (PDA) Vaccines Interest Group (VIG) authored and published PDA Technical Report No. 89 Strategies for Vaccine Development and Lifecycle Management (TR 89) which seeks to provide context to vaccine developers and manufacturers regarding key aspects of new or legacy vaccines such as control strategy from process development to vaccine lifecycle management, comparability and lifecycle management including technical, validation, quality and regulatory perspectives. To further explain and illustrate the concepts and topics discussed, seven relevant situations were selected as either case studies associated with changes implemented or proposed process development strategies, which are discussed in this article. The situations described are: working cell bank, modification or update of externally supplied product contact components for vaccine manufacturing, raw material change, new product at an existing site, vaccine development acceleration by leveraging existing platforms, selection and implementation of potency method, and modeling for stability forecast prediction. For each situation, the applicable key concepts from TR#89 are discussed as follows: Control Strategy, Prior Knowledge, Relying on PQS, Classification of Parameters, Validation Approach, Use of a Risk-based Approach, Comparability, Use of ICHQ12 and Additional Regulatory Considerations.

Pseudorabies Virus Glycoproteins E and B Application in Vaccine and Diagnosis Kit Development.

Background: Pseudorabies virus (PRV) is a highly infectious pathogen that affects a wide range of mammals and imposes a significant economic burden on the global pig industry. The viral envelope of PRV contains several glycoproteins, including glycoprotein E (gE) and glycoprotein B (gB), which play critical roles in immune recognition, vaccine development, and diagnostic procedures. Mutations in these glycoproteins may enhance virulence, highlighting the need for updated vaccines. Method: This review examines the functions of PRV gE and gB in vaccine development and diagnostics, focusing on their roles in viral replication, immune system interaction, and pathogenicity. Additionally, we explore recent findings on the importance of gE deletion in attenuated vaccines and the potential of gB to induce immunity. Results: Glycoprotein E (gE) is crucial for the virus's axonal transport and nerve invasion, facilitating transmission to the central nervous system. Deletion of gE is a successful strategy in vaccine development, enhancing the immune response. Glycoprotein B (gB) plays a central role in viral replication and membrane fusion, aiding viral spread. Mutations in these glycoproteins may increase PRV virulence, complicating vaccine efficacy. Conclusion: With PRV glycoproteins being essential to both vaccine development and diagnostic approaches, future research should focus on enhancing these components to address emerging PRV variants. Updated vaccines and diagnostic tools are critical for combating new, more virulent strains of PRV.

Enhanced production of recombinant coxsackievirus A16 using a serum-free HEK293A suspension culture system for bivalent enterovirus vaccine development

Coxsackievirus A16 (CVA16) is one of the primary pathogens that causes hand, foot, and mouth disease (HFMD) in young children. In previous studies, CVA16 vaccine development has encountered several challenges, such as inefficient replication of the CVA16 virus in present culture systems, the induction of only mild neutralizing antibody titers, and neutralizing antibodies induced by certain vaccine candidates that are unable to protect against CVA16 viral challenge. In this study, we constructed a DNA-launched CVA16 infectious clone (CVA16ic) based on the genomic sequence of the CVA16 N5079 strain to minimize interference from viral quasispecies. The biochemical properties of this CVA16ic strain were similar to those of its parental strain. Serum-free HEK293A suspension cells, which produced higher virus titers than Vero cells, were demonstrated to improve CVA16 production yields. In addition, our study showed that inactivated EV-A71 antigens could enhance the immunogenicity of inactivated CVA16 mature/full particles (F-particles), suggesting that a bivalent CVA16 and EV-A71 vaccine may be an effective strategy for CVA16 vaccine development. These findings are expected to provide novel strategies and accelerate the development of bivalent HFMD vaccines.

Strategy against super-resistant bacteria: Curdlan-induced trained immunity combined with multi-epitope subunit vaccine

Methicillin-resistant Staphylococcus aureus (MRSA) is rapidly spreading worldwide, emerging as a leading cause of bacterial infections in healthcare and community settings. This poses serious risks to human health. The shortage of novel antibiotics and the absence of effective vaccines make MRSA particularly challenging to treat. Existing vaccine development strategies often fail to provide early protection against infections, highlighting the urgent need for solutions. Herein, we propose a novel strategy combining trained immunity with a multi-epitope subunit vaccine to combat MRSA infections. We comprehensively evaluated the trained immune phenotypes induced by β-glucan from barley and curdlan. Macrophages trained with curdlan exhibited a more balanced inflammatory response compared to β-glucan from barley, expressing higher levels of IL-1β, IFN-β, TGF-β, and CCL2 upon secondary stimulation. Furthermore, curdlan-induced trained immunity rapidly provided excellent protection against S. aureus infection in mice. RNA-sequencing analysis revealed that curdlan modulates the Wnt signaling pathway in macrophages, resolves inflammation, and promotes tissue repair. When combined with one or two doses of S. aureus multivalent epitope antigen against MRSA infection, curdlan-induced trained immunity enhanced early protection and promoted recovery. Our study demonstrates the feasibility of combining trained immunity with vaccine protection against MRSA, providing a strategy against multi-drug resistant bacteria.

The Mpox outbreak is a public health emergency of international concern: Implications for mental health and global preparedness.

The Mpox, a zoonotic viral disease that has historically affected Central and West Africa, has been declared a Public Health Emergency of International Concern by the World Health Organization. Rapid transmission and recent dissemination in Africa may imply significant challenges to global health, including mental health. We reviewed the mental health implications of the Mpox outbreak according to the published literature. We also discussed the psychological effects of the global spreading of this infection and public health preparedness strategies. Key areas of intervention may include the epidemiological surveillance, vaccine development, and mental health strategies. The Mpox outbreak calls for a robust global preparedness to address potential health emergencies. Strengthening epidemiological surveillance, ensuring equitable vaccine distribution, and building resilient public health infrastructure are crucial. Additionally, addressing mental health consequences may require immediate, intermediate, and long-term strategies, including telepsychiatry, stress management training, and the integration of mental health into primary care.

Novel SARS-COV2 poly epitope phage-based candidate vaccine and its immunogenicity

Background and purpose: The global emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted widespread concern. Bacteriophages have recently gained attention as a cost-effective and stable alternative for vaccine development due to their adjuvant properties. This study aimed to design and validate a poly epitope composed of viral proteins. Experimental approach: SARS-CoV-2 proteins (spike, nucleocapsid, membrane, envelope, papain-like protease, and RNA-dependent RNA polymerase) were selected for analysis. Immunoinformatic methods were employed to predict B and T cell epitopes, assessing their antigenicity, allergenicity, and toxicity. Epitopes meeting criteria for high antigenicity, non-allergenicity, and non-toxicity were linked to form poly epitopes. These sequences were synthesized and cloned into pHEN4 plasmids to generate Poly1 and Poly2 phagemid vectors. Recombinant Poly1 and Poly2 phages were produced by transforming M13ΔIII plasmids and phagemid vectors into E. coli TG1. Female Balb/c mice were immunized with a cocktail of Poly1 and Poly2 phages, and their serum was collected for ELISA testing. Interferon-gamma (IFN-γ) testing was performed on spleen-derived lymphocytes to evaluate immune system activation. Findings/Results: Recombinant Poly1 and Poly2 phages were produced, and their titer was determined as 1013 PFU/mL. Efficient humoral immune responses and cellular immunity activation in mice were achieved following phage administration. Conclusion and implication: Poly epitopes displayed on phages exhibit adjuvant properties, enhancing humoral and cellular immunity in mice. This suggests that phages could serve as adjuvants to bolster immunity against SARS-Cov-2. Recombinant phages could be applied as effective candidates for injectable and oral vaccine development strategies.

SARS-CoV-2 Evolution: Immune Dynamics, Omicron Specificity, and Predictive Modeling in Vaccinated Populations.

Host immunity is central to the virus's spread dynamics, which is significantly influenced by vaccination and prior infection experiences. In this work, we analyzed the co-evolution of SARS-CoV-2 mutation, angiotensin-converting enzyme 2 (ACE2) receptor binding, and neutralizing antibody (NAb) responses across various variants in 822 human and mice vaccinated with different non-Omicron and Omicron vaccines is analyzed. The link between vaccine efficacy and vaccine type, dosing, and post-vaccination duration is revealed. The classification of immune protection against non-Omicron and Omicron variants is co-evolved with genetic mutations and vaccination. Additionally, a model, the Prevalence Score (P-Score) is introduced, which surpasses previous algorithm-based models in predicting the potential prevalence of new variants in vaccinated populations. The hybrid vaccination combining the wild-type (WT)inactivated vaccine with the Omicron BA.4/5 mRNA vaccine may provide broad protection against both non-Omicron variants and Omicron variants, albeit with EG.5.1 still posing a risk. In conclusion, these findings enhance understanding of population immunity variations and provide valuable insights for future vaccine development and public health strategies.

Formation of adaptive immunity against salmonellosis in cows using effector memory cells

The study aimed to investigate how the number of effector memory cells changes under the influence of a Salmonella vaccine antigen in cows. A homogeneous group of 100 Holstein-Friesian cows, kept under the same conditions, had blood samples taken. The blood was collected at four time points: before the first vaccination, and 7, 45, and 56 days after. The cows also received a booster vaccination on days 8-10. They were immunised with a polyvalent vaccine against livestock salmonellosis in Kazakhstan. Blood was separated into plasma and cellular fractions by centrifugation at 1,500 rpm for 10 minutes. The cellular fraction was then analysed by flow cytometry to determine the number of CD4+, CD8+, and γδ T-cell subpopulations at the four time points: before vaccination, and at 7-, 45-, and 56-days post-vaccination. Analysis of over 10,000 cells from each sample was conducted using FlowJo software. The data showed that the population of CD4+ and CD8+ T-lymphocytes and γδ T-cells increased 1.5 times by day 7 after the initial vaccination. The cows then received a booster dose on days 8-10, and by day 45 after the first vaccination, the CD4+ and CD8+ T-lymphocyte and γδ T-cell populations had increased threefold. CD45RA+ T-lymphocytes and γδ T-cells demonstrated a steady increase by day 45, followed by a decline in the numbers of T-cells across all phylogenetic groups. Thus, it can be concluded that the primary vaccination stimulates the development of long-term immune memory, while the booster dose triples the number of CD4+, CD8+, and γδ T-cell subpopulations. The findings provide insights into the mechanism of adaptive immunity formation in cows against salmonellosis through the use of effector memory cells and may be applied in developing vaccination strategies for cattle