Vaccine Components Research Articles

Revolutionizing Nanovaccines: A New Era of Immunization

Infectious diseases continue to pose a significant global health threat. To combat these challenges, innovative vaccine technologies are urgently needed. Nanoparticles (NPs) have unique properties and have emerged as a promising platform for developing next-generation vaccines. Nanoparticles are revolutionizing the field of vaccine development, offering a new era of immunization. They allow the creation of more effective, stable, and easily deliverable vaccines. Various types of NPs, including lipid, polymeric, metal, and virus-like particles, can be employed to encapsulate and deliver vaccine components, such as mRNA or protein antigens. These NPs protect antigens from degradation, target them to specific immune cells, and enhance antigen presentation, leading to robust and durable immune responses. Additionally, NPs can simultaneously deliver multiple vaccine components, including antigens, and adjuvants, in a single formulation, simplifying vaccine production and administration. Nanovaccines offer a promising approach to combat food- and water-borne bacterial diseases, surpassing traditional formulations. Further research is needed to address the global burden of these infections. This review highlights the potential of NPs to revolutionize vaccine platforms. We explore their mechanisms of action, current applications, and emerging trends. The review discusses the limitations of nanovaccines, innovative solutions and the potential role of artificial intelligence in developing more effective and accessible nanovaccines to combat infectious diseases.

DNA Nanostructures-Based In Situ Cancer Vaccines: Mechanisms and Applications.

Current tumor vaccines suffer from inadequate immune responsive due to the insufficient release of tumor antigens, low tumor infiltration, and immunosuppressive microenvironment. DNA nanostructures with their ability to precisely engineer, controlled release, biocompatibility, and the capability to augment the immunogenicity of tumor microenvironment, have gained significant attention for their potential to revolutionize vaccine designing. This review summarizes various applications of DNA nanostructures in the construction of in situ cancer vaccines, which can generate tumor-associated antigens directly from damaged tumors for cancer immune-stimulation. The mechanisms and components of cancer vaccines are listed, the specific strategies for constructing in situ vaccines using DNA nanostructures are explored and their underlying mechanisms of action are elucidated. The immunogenic cell death (ICD) induced by chemotherapeutic agents, photothermal therapy (PTT), photodynamic therapy (PDT), and radiation therapy (RT) and the related cancer vaccines building strategies are systematically summarized. The applications of different DNA nanostructures in various cancer immunotherapy are elaborated, which exerts precise, long-lasting, and robust immune responses. The current challenges and future prospectives are proposed. This review provides a holistic understanding of the evolving role of DNA nanostructures for in situ vaccine development.

A Roadmap Towards the Identification and Validation of Conserved T Cell Epitope Regions in Viral Pathogen Families with Pandemic Potential.

The SARS-CoV-2 pandemic has highlighted the need for society, as a whole, to be prepared against potential pandemics caused by a variety of different viral families of concern. Here, we describe a roadmap towards the identification and validation of conserved T cell epitope regions from Viral Families of Pandemic Potential (VFPP). For each viral family, we select a prototype virus, the sequence of which could be utilized in epitope identification screens. Examples of viral families considered and their respective prototypes (species/ subspecies) are Coronaviridae (Severe Acute Respiratory Syndrome-related Coronavirus/ SARS-CoV-2), Flaviviridae (Dengue virus/DENV2), Togaviridae (Chikungunya virus/ CHIKV), Paramyixoviridae (Morbillivirus/measles), Arenaviridae (Mammarenavirus/ Lassa), and Picornaviridae (Enterovirus C/poliovirus). The peptide sequences encoded in each prototype virus are then analyzed to determine their conservation across different viral taxonomic groups and viral variants derived from each of the VFPP. We outline available methodologies for epitope discovery based on panels of overlapping peptides and bioinformatics- based predictions of HLA-peptide binding, along with high-throughput in vitro assays, with emphasis on addressing coverage of the general worldwide population. Validation can be achieved by a variety of methodologies, including determining HLA restriction and recognition in samples from volunteers convalescent from previous infections or immunized with approved or experimental vaccines, and immunophenotyping of responding T cells. The capacity of these regions to induce crossreactive T cell responses can be tested experimentally with homologous peptides derived from the various viral species of interest. Importantly, they could be considered as a component of pan-viral family vaccines. Conversely, immunogenic regions that are highly specific to a given virus could be of interest for diagnostic applications.

Spatiotemporal Dynamic Immunomodulation by Infection-Mimicking Gels Enhances Broad and Durable Protective Immunity Against Heterologous Viruses.

Despite their safety and widespread use, conventional protein antigen-based subunit vaccines face significant challenges such as low immunogenicity, insufficient long-term immunity, poor CD8+ T-cell activation, and poor adaptation to viral variants. To address these issues, an infection-mimicking gel (IM-Gel) is developed that is designed to emulate the spatiotemporal dynamics of immune stimulation in acute viral infections through in situ supramolecular self-assembly of nanoparticulate-TLR7/8a (NP-TLR7/8a) and an antigen with tannic acid (TA). Through collagen-binding properties of TA, the IM-Gel enables sustained delivery and enhanced retention of NP-TLR7/8a and protein antigen in the lymph node subcapsular sinus of mice for over 7 days, prolonging the exposure of vaccine components in both B cell and T cell zones, leading to robust humoral and cellular responses. The IM-Gel system with the influenza A antigen confers cross-protection against multiple influenza subtypes (H1N1, H5N2, H3N2, H7N3, and H9N2) with long-term immune responses. Combination of the IM-Gel with the SARS-CoV-2 spike protein also elicits strong cross-reactive antibody responses against multiple SARS-CoV-2 variants (Alpha, Beta, NY510+D614G, Gamma, Kappa, and Delta). The IM-Gel, as a programmable immunomodulatory material, provides a vaccine design principle for the development of next-generation universal vaccines that can elicit broad and durable protective immunity against emerging viruses.

Expert consensus on the benefits of neuraminidase in conventional influenza vaccines: a Delphi study

BackgroundSeasonal vaccination is the mainstay of human influenza prevention. Licensed influenza vaccines are regularly updated to account for viral mutations and antigenic drift and are standardised for their haemagglutinin content. However, vaccine effectiveness remains suboptimal. Neuraminidase (NA) evolves more gradually than hemagglutinin and has been demonstrated to provide added clinical benefits. However, NA is not currently a mandated or standardised component of influenza vaccines.MethodsHere, we collated expert opinions on the importance of NA in influenza vaccines in a two-stage Delphi survey. Nine statements about NA were formulated by a steering committee based on a targeted literature review. In the survey’s first round, panellists recruited from three continents were requested to report on their agreement with each statement and estimate the strength of evidence for each statement. Panellists were also requested to explain their choice of answer and suggest revisions to the statements. Consensus was considered reached if ≥ 75% of panellists agreed with a statement. If consensus was not reached for a statement, this statement was revised and included in the survey’s second round.ResultsNine panellists with a broad range of NA-related expertise, including clinical, research, and public health experience, completed the survey. They agreed that anti-NA responses acquired via natural infection or vaccination are associated with protective immunity independently of haemagglutinin and that NA provided additional advantages including improving disease severity metrics. The experts identified several knowledge gaps concerning heterologous cross-reactivity of vaccine-induced anti-NA antibodies, correlations between anti-NA titres and reduced transmission or infection risks, and differences in anti-NA responses to seasonal influenza vaccines.ConclusionsNA is an important influenza vaccine component and is associated with specific benefits. These benefits would likely be greater if NA content were standardised. Additional research is needed to optimise vaccines for anti-NA effects.

Vaccine Specifically for Immunocompromised Individuals against Superbugs.

Immunocompromised populations, including cancer patients, elderly individuals, and those with chronic diseases, are the primary targets of superbugs. Traditional vaccines are less effective due to insufficient or impaired immune cells. Inspired by the "vanguard" effect of neutrophils (NE) during natural infection, this project leverages the ability of NE to initiate the NETosis program to recruit monocytes and DC cells, designing vaccines that can rapidly recruit immune cells and enhance the immune response. The PLGA microsphere vaccine platform (MSV) with a high level of safety contains whole-bacterial antigens both internally and externally, providing initial and booster effects through programmed distribution and release of antigens after a single injection. Experimental data indicate that immunizing mice with a mixture of MSV and NE induces the formation of spontaneous gel-like neutrophil extracellular traps (NETs) at the inoculation site. These NETs recruit immune cells and prevent the diffusion of vaccine components, thereby reducing damage from bacterial toxins and enhancing vaccine biosafety. This strategy shows excellent efficacy against MRSA-induced infections in not only healthy but also immunocompromised mice.

Poria cocos polysaccharide-honeycomb manganese oxide nanoparticles as a vaccine adjuvant to induce potent immune responses

As indispensable components of vaccines, adjuvants play a critical role in inducing potent immune responses. In our previous study, we isolated and purified a water-soluble polysaccharide from Poria cocos (PCP), and found that the PCP had the potential to act as an immunostimulant to induce a balanced Th1/Th2 immune response. However, the PCP showed effective immunomodulatory activity only at high concentrations. Herein, we prepared a novel and biodegradable adjuvant system (PCP-hMnOx), in which the PCP was loaded onto the honeycomb manganese oxide nanoparticles (hMnOx). The developed PCP-hMnOx adjuvant system not only acted as an immunostimulant, but also as a delivery system to enhance antigen uptake by antigen-presenting cells (APCs), stimulate the activation of APCs and facilitate the formation of germinal center in draining lymph nodes. Furthermore, the PCP-hMnOx adjuvant system facilitated the antibody production, the activation of CD4+ and CD8+ T cells, and the generation of IFN-γ, thus inducing a robust and durable immune response with a balanced Th1/Th2 response in comparison to commercial alum adjuvant. Our results demonstrated that the PCP-hMnOx adjuvant system improved the immunomodulatory activity of the PCP, and had the potential to provide a simple, safe, and efficient nanoparticles-based strategy to induce potent immune responses.

Transcriptional Systems Vaccinology Approaches for Vaccine Adjuvant Profiling.

Adjuvants are a diverse group of substances that can be added to vaccines to enhance antigen-specific immune responses and improve vaccine efficacy. The first adjuvants, discovered almost a century ago, were soluble crystals of aluminium salts. Over the following decades, oil emulsions, vesicles, oligodeoxynucleotides, viral capsids, and other complex organic structures have been shown to have adjuvant potential. However, the detailed mechanisms of how adjuvants enhance immune responses remain poorly understood and may be a barrier that reduces the rational selection of vaccine components. Previous studies on mechanisms of action of adjuvants have focused on how they activate innate immune responses, including the regulation of cell recruitment and activation, cytokine/chemokine production, and the regulation of some "immune" genes. This approach provides a narrow perspective on the complex events involved in how adjuvants modulate antigen-specific immune responses. A comprehensive and efficient way to investigate the molecular mechanism of action for adjuvants is to utilize systems biology approaches such as transcriptomics in so-called "systems vaccinology" analysis. While other molecular biology methods can verify if one or few genes are differentially regulated in response to vaccination, systems vaccinology provides a more comprehensive picture by simultaneously identifying the hundreds or thousands of genes that interact with complex networks in response to a vaccine. Transcriptomics tools such as RNA sequencing (RNA-Seq) allow us to simultaneously quantify the expression of practically all expressed genes, making it possible to make inferences that are only possible when considering the system as a whole. Here, we review some of the challenges in adjuvant studies, such as predicting adjuvant activity and toxicity when administered alone or in combination with antigens, or classifying adjuvants in groups with similar properties, while underscoring the significance of transcriptomics in systems vaccinology approaches to propel vaccine development forward.

Octahedral small virus-like particles of dengue virus type 2.

Ectopic expression of flavivirus envelope (E) and precursor M (prM) proteins leads to the formation and secretion of empty, virus-like particles (VLPs). We show that a major class of VLPs, of smaller diameter than those of virion size ("small VLPs": smVLPs), are octahedrally symmetric particles. The known characteristics of immature virions (asymmetric trimers of prM-E heterodimers) allow us to understand the assembly of an octahedral (rather than icosahedral) surface lattice. Cleavage of prM and formation of mature, fusogenic smVLPs yield somewhat irregular, ovoid particles. These observations are directly relevant to proposals for using immunogenic but non-infectious VLPs as components of specific flavivirus vaccines.

Controlling vaccine kinetics using tannic acid for enhanced humoral immunity.

Despite the success of global vaccination campaigns, vaccine access in low-resource settings is an ongoing challenge. Subunit vaccines are a well-established and clinically scalable intervention, yet they have achieved limited success for poorly immunogenic antigens such as those associated with SARS-CoV-2. Delivery strategies that promote gradual release of subunit vaccines from the injection site offer the potential to improve humoral immunity by enhancing lymph node exposure, however, clinical implementation of this strategy is challenging due to poor scalability and high costs. Here, we propose an approach that uses the polyphenol tannic acid (TA) as a simple and inexpensive strategy to enhance tissue residence of vaccines and subsequent humoral immunity. We show that TA mediates supramolecular interactions between vaccine components and tissue at the subcutaneous injection site to promote extended retention of protein antigens for over one week. In addition to enhancing the magnitude and duration of vaccine drainage to the lymph nodes, inclusion of TA improved accumulation of activated, antigen-laden monocyte-derived dendritic cells (moDCs), promoting long-lasting humoral immunity against the receptor-binding domain (RBD) of SARS-CoV-2 and variants of concern. This system, termed TAPER (Tannic Acid-Promoted Enhanced Retention) provides various translational advantages including one-pot synthesis, scalability, low cost, and modularity, towards realization of effective and accessible subunit vaccines.

Regulating Immune Responses Induced by PEGylated Messenger RNA-Lipid Nanoparticle Vaccine.

Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activate adaptive immunity. mRNAs can bind to various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), and increase the production of inflammatory cytokines. This review summarizes mechanisms of innate immunity induced by mRNAs. Polyethylene glycol (PEG) has been employed as a component of the mRNA-LNP vaccine. PEGylated nanoparticles display enhanced stability by preventing aggregation of particles. However, PEGylation can cause adverse reactions, including blood clearance (ABC) of nanoparticles via complement activation and anaphylaxis. Mechanisms of PEG-induced ABC phenomenon and anaphylaxis are presented and discussed. There have been studies aimed at reducing immune responses associated with PEG to make safe and effective vaccines. Effects of modifying or replacing PEG in reducing immune responses associated with PEGylated nanoparticles are also discussed. Modifying mRNA can induce immune tolerance, which can prevent hypersensitivity reactions induced by PEGylated mRNA-LNP vaccines. Current progress of immune tolerance induction in association with mRNA-LNP is also summarized. This review might be helpful for developing safe and effective PEGylated mRNA-LNP vaccines.

Immunogenicity, Reactogenicity, and Safety of a Pentavalent Meningococcal ABCWY Vaccine in Adolescents and Young Adults who had Previously Received a Meningococcal ACWY Vaccine: Phase 3, Randomized, Controlled Clinical Study.

A MenABCWY vaccine containing 4CMenB and MenACWY-CRM vaccine components has been developed to protect against the five meningococcal serogroups that cause most invasive disease cases. In this phase 3 study (NCT04707391), healthy participants aged 15-25 years, who had received MenACWY vaccination ≥4 years previously, were randomized (1:1) to receive two MenABCWY doses six months apart or one MenACWY-CRM dose. Primary objectives were to demonstrate the non-inferiority of MenABCWY 1 month post-vaccination versus MenACWY-CRM, with a lower limit of 2-sided 95% confidence interval above -10% for group differences in 4-fold rise in human serum bactericidal antibody (hSBA) titers against serogroups ACWY, and to evaluate reactogenicity and safety. Secondary endpoints included percentages of participants with hSBA titers ≥lower limit of quantitation (LLOQ) against serogroups ACWY and vaccine antigen-specific serogroup B (MenB) indicator strains. Non-inferiority of MenABCWY versus MenACWY-CRM was demonstrated following each MenABCWY dose. Percentages of participants with hSBA titers ≥LLOQ for serogroups ACWY were 97.9-98.9% and 99.5-100% following one and two MenABCWY doses, respectively, and 96.8-99.0% following one MenACWY-CRM dose. After two MenABCWY doses, 75.6-96.3% of participants had hSBA titers ≥LLOQ against MenB indicator strains. The MenABCWY vaccine was well tolerated in MenACWY-primed individuals with a favorable safety profile. Immune responses against serogroups ACWY following one and two doses of investigational MenABCWY vaccine are non-inferior to those following MenACWY-CRM in MenACWY-primed adolescents and young adults. Robust immune responses were observed against MenB indicator strains after two MenABCWY doses administered 6 months apart.

A CRISPRi Library Screen in Group B Streptococcus Identifies Surface Immunogenic Protein (Sip) as a Mediator of Multiple Host Interactions.

Group B Streptococcus (GBS; Streptococcus agalactiae) is an important pathobiont capable of colonizing various host environments, contributing to severe perinatal infections. Surface proteins play critical roles in GBS-host interactions, yet comprehensive studies of these proteins' functions have been limited by genetic manipulation challenges. This study leveraged a CRISPR interference (CRISPRi) library to target genes encoding surface-trafficked proteins in GBS, identifying their roles in modulating macrophage cytokine responses. Bioinformatic analysis of 654 GBS genomes revealed 66 conserved surface protein genes. Using a GBS strain expressing chromosomally integrated dCas9, we generated and validated CRISPRi strains targeting these genes. THP-1 macrophage-like cells were exposed to ethanol-killed GBS variants, and pro-inflammatory cytokines TNF-α and IL-1β were measured. Notably, knockdown of the sip gene, encoding the Surface Immunogenic Protein (Sip), significantly increased IL-1β secretion, implicating Sip in caspase-1-dependent regulation. Further, Δsip mutants demonstrated impaired biofilm formation, reduced adherence to human fetal membranes, and diminished uterine persistence in a mouse colonization model. These findings suggest Sip modulates GBS-host interactions critical for pathogenesis, underscoring its potential as a therapeutic target or vaccine component.

Unique Kinetics of the Human Milk Antibody Response to JYNNEOS Vaccine for Prevention of Monkey Pox: A Case Study.

Background: JYNNEOS is a nonreplicating modified vaccinia Ankara vaccine currently licensed to prevent monkeypox infection, and its milk immunogenicity remains unstudied. Objective: Investigate the human milk immunogenicity of the JYNNEOS vaccine in one individual and examine the milk for evidence of vaccine components. Methods: Immunogenicity of milk and plasma samples were tested by Luminex assays against Vaccinia antigens, and vaccine components were tested using PCR and sandwich ELISA. Results: Plasma antibody (Ab) response increased up to 3.7-fold in immunoglobulin G (IgG) titer and 1.4-fold in IgA compared with baseline, confirming vaccine immunogenicity in this participant 2 weeks post dose 2. Specific plasma IgG remained 1.2- to 1.7-fold above baseline 12 weeks post dose 2, while IgA returned to baseline levels. Notably, the milk response exhibited unique kinetics, particularly for IgA. Milk IgA against all three antigens increased 0.9- to 2.2-fold 2 weeks post dose 2, reaching a peak titer increase of 1.1- to 2.7-fold at 12 weeks post dose 2. Secretory (s) Ab levels increased to 1.1- to 2-fold at 2 weeks post dose 2 and reached a peak of 2- to 3.2-fold increase at the 12-week time point. Importantly, IgA and sAb responses in milk exhibited correlation, suggesting most milk IgA was sIgA. Notably, no vaccine components (VACV protein or DNA) were detected in the milk samples. Conclusion: These data suggest that the milk Ab response to this intradermal (ID) VACV-based vaccine is distinct from that observed systemically, indicating a unique mucosal immune response and highlighting its potential to elicit protective long-lasting sIgA. This case report provides strong evidence for inclusion of this vaccine platform in future studies of maternal vaccines aimed to elicit a protective milk Ab response.

Personalized Membrane Protein Vaccine Based on a Lipid Nanoparticle Delivery System Prevents Postoperative Recurrence in Colorectal Cancer Models

While accessing tumor neoantigens and developing effective delivery systems have posed significant challenges in therapeutic oncology vaccines, this study introduces a cost- and time-efficient personalized tumor vaccine demonstrating potent anti-tumor effects in a mouse xenograft model. This vaccine utilizes a lipid nanoparticle (C5 LNP) system loaded with membrane protein antigens (mAg) derived from surgically excised tumor tissue. Its safety and efficacy were validated in a B16-OVA murine model. C5/OVA exhibited significant uptake by dendritic cells (DCs), leading to cross-presentation, maturation, and subsequent initiation of robust cell-mediated and humoral immune responses. This resulted in clear tumor growth suppression and extended survival in the B16-OVA model. Furthermore, the personalized C5/mAg vaccine effectively inhibited tumor growth in a colorectal carcinoma model. When combined with anti-PD-1 therapy, it notably increased complete remission (CR) rates in the CT26 xenograft model. Vaccinated mice demonstrated 100% resistance to tumor rechallenge, underscoring the vaccine's ability to induce long-term immune memory. This study presents a promising personalized cancer vaccine delivery system with potential for both treatment and prevention of carcinoma in clinical applications. Statement of significanceIn this paper, we present a scheme for manufacturing personalized tumor vaccines. The vaccine component consists of lipid nanoparticles (LNPs) designated C5 and membrane protein antigens (mAg) derived from autologous tumor tissue surgically resected from the patient. Our study demonstrates that the personalized mAg-C5 vaccine for colorectal carcinoma significantly inhibits tumor growth. Furthermore, conjugation with anti-PD-1 therapy demonstrably increased the complete remission (CR) rate in the murine CT26 xenograft tumor model. Additionally, mice treated with the C5/mAg vaccine exhibited 100% resistance to tumor growth in a colon carcinoma rechallenge model, indicating the induction of immune memory by the vaccine.Our research results suggest that the mAg-LNP vaccine is a simple, cost-effective treatment that clinicians can easily and quickly integrate into routine practice.

Protective Antimicrobial Effect of the Potential Vaccine Created on the Basis of the Structure of the IgA1 Protease from Neisseria meningitidis.

Background/Objectives: IgA1 protease is one of the virulence factors of Neisseria meningitidis, Haemophilus influenzae and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A28-P1004 from N. meningitidis serogroup B strain H44/76. These proteins are potential components of an antimeningococcal vaccine for protection against infections caused by pathogenic strains of N. meningitidis and other bacteria producing serine-type IgA1 proteases. Methods: To obtain promising antigens for creating a vaccine, we designed and obtained several recombinant proteins. These proteins consisted of single or directly connected fragments selected from various regions of the IgA1 protease A28-P1004. The choice of these fragments was based on our calculated data on the distribution of linear and conformational B-cell epitopes and MHC-II T-cell epitopes in the structure of IgA1 protease, taking into account the physicochemical properties of potential compounds and the results of a comparative analysis of the spatial structures of the original IgA1 protease and potential recombinant proteins. We studied the immunogenic and protective effects of the obtained proteins on the BALB/c mice against meningococci of serogroups A, B and C. Results: Proteins MA28-P1004-LEH6, MW140-K833-LEH6, MW329-P1004-LEH6, M(W140-H328)-(W412-D604)-(Y866-P1004)-LEH6 and M(W140-Q299)-(Y866-P1004)-LEH6 have shown the following antibody titers, 103/titer: 11 ± 1, 6 ± 2, 6 ± 1, 9 ± 1 and 22 ± 3, respectively. Also, the last two proteins have shown the best average degree of protection from N. meningitidis serogroups A, B and C, %: 62 ± 6, 63 ± 5, 67 ± 4 respectively for M(W140-H328)-(W412-D604)-(Y866-P1004)-LEH6 and 70 ± 5, 66 ± 6, 83 ± 3 respectively for M(W140-Q299)-(Y866-P1004)-LEH6. Conclusions: We selected two recombinant proteins consisting of two (M(W140-Q299)-(Y866-P1004)-LEH6) or three (M(W140-H328)-(W412-D604)-(Y866-P1004)-LEH6) linked fragments of IgA1 protease A28-P1004 as candidate active component for an antimeningococcal vaccine.

Advances in Vaccine Adjuvants for Teleost Fish: Implications for Aquatic Welfare and the Potential of Nanoparticle-Based Formulations.

Vaccine adjuvants are crucial for reinforcing the immunogenicity of vaccines. Therefore, they are widely used in the aquaculture sector as vaccine components, facilitating the efficient prevention of infectious diseases and promoting sustainable teleost fish growth. Despite their benefits, there has been a growing concern about the potential adverse effects of vaccine adjuvants in teleost fish, connoting a valid impact on their overall health and welfare. Among the adjuvants used in aquaculture vaccinology, nanoparticle-based formulations have given rise to a promising new alternative to traditional options, such as oil-based emulsions and aluminum compounds, offering the benefit of minimizing relevant side effects. The aim of this paper was to review the current status of the adjuvants used in aquaculture, provide a description and an evaluation of their mode of action and side effects, and explore the potential use of nanoparticle formulations as adjuvants to improve the efficacy of aquaculture vaccines. By demonstrating and assessing the equilibrium between teleost fish welfare and immunological efficacy, this review presents a collective perspective that will assist in establishing a framework for the utilization of effective species-specific practices around adjuvant use in aquaculture, while also addressing the challenges of welfare-friendly immunization.

In silicon desinging of RANKL-targeting vaccine for protection of osteoporosis based on the epitope of Denosumab

BackgroundLife quality of osteoporosis patients is affected significantly due to the severely complications of fracture and pain. RANKL, indicated as the key mediator of osteoporosis, plays a pathogenic role of osteoclasts induction. To target this program, two medications, bisphosphonate and Denosumab, were developed and achieved remarkable advantages in clinics. Unfortunately, fracture-related side-effects always emerge unavoidably, after either long-term administration of bisphosphonates or Denosumab withdrawing. To address these challenges, vaccine-based approach has been adopted to achieve sustainable protection through induction and maintenance of effective antibodies in mild level over decades. MethodsA Denosumab binding peptide was firstly identified as the basic component of vaccine. This peptide was then fused with diphtheria toxin T domain, a widely used adjuvant protein. Its capabilities to penetrate the autologous tolerance and induce the immune responses was then demonstrated with in-silicon evaluation. Finally, the efficacy of the DR3 vaccine was assessed through immunization on the human RANKL transgenic mice model of osteoporosis. ResultsThe DTT-RANKL(220–245)3 vaccine, termed as DR3, were predicted as highly antigenic and non-allergenicity. This molecule was comprised of 46.5 % of helix, 8.5 % strand and 45.1 % coil, the optimized Z-value of the tertiary structure was 6.39, and the favored area in the Ramachandran plot was 96.1 % after refinement. Molecular docking showed a tight binding of DR3 vaccine to TLR2 (−9.2 kcal/mol) and TLR4 (−9.5 kcal/mol). In addition, the immune stimulation indicated robust responses post administration of DR3 vaccine, including high level production of of antibodies and cytokines, activated T and B lymphocytes, and the long-last immune memory. In agree with the simulation, vaccinated mice generated high titers anti-hRANKL antibodies and elevated levels of IL-4 and IL-10 at 7th week post immunization. ConclusionDR3 vaccine was aroused to benefit the prevention and treatment of osteoporosis, and other bone-resorptive diseases potentially.

Mono-Palmitoyl-N-Alkylurea Ligands as Specific Activators of Human Toll-Like Receptor 2/6 Heterodimer.

Ligands for Toll-like-receptor 2 (TLR2) have demonstrated significant potential as immune-stimulating components in synthetic vaccines. Activation of TLR2 relies on the formation of dimeric complexes with either TLR1 or TLR6 and the nature of these dimers can impact therapeutic outcomes. The lipopeptide-based TLR2 ligands Pam3CysSK4 and Pam2CysSK4 have been extensively studied, and their recognition by different TLR-receptor heterodimers, TLR2/TLR1 and TLR2/TLR6, respectively, has been established. However, the high lipophilicity of these ligands, containing multiple palmitoyl residues, can result in solubility issues when used as vaccine adjuvants. To address this, we previously synthesized a less lipophilic ligand containing a single palmitoyl chain called mini-UPam, which effectively stimulates human moDC maturation. We here probe the receptor-dimer specificity of several mini-Upam derivatives and reveal that these mini-UPam are hTLR2/TLR6 selective ligands and that the introduction of longer urea alkyl chains does not shift the binding specificity to hTLR2/TLR1 heterodimers, in contrast to their Pam2CysSK4 and Pam3CysSK4 counterparts, pointing to a different binding mode of the UPam ligands.

National Influenza Annual Report 2023-2024: A focus on influenza B and public health implications.

The 2023-2024 influenza epidemic saw the return of typical late-season influenza B circulation. The epidemic was declared in week 45 (week ending November 11, 2023) due to the predominant circulation of influenza A(H1N1) and peaked in week 52 (week ending December 30, 2023); however, as influenza A circulation decreased, influenza B detections and the percentage of tests positive increased, reaching its peak in week 14 (week ending April 6, 2024). Influenza B/Victoria dominated this wave of activity, contributing to the ongoing discussion about the apparent disappearance of influenza B/Yamagata. With the recommendation for the removal of influenza B/Yamagata lineages from the recommended seasonal influenza vaccine components, the influenza surveillance community is preparing for the possibility of a new seasonal pattern dominated by influenza B/Victoria circulation. This season, as a result of influenza B/Victoria's overwhelming predominance, younger age groups were primarily affected by the wave of influenza B activity. Over the course of the season, among all influenza B detections, 52% occurred in children aged 0-19 years. Among all influenza B-associated hospitalizations, 46.4% were in children aged 0-19 years, and the highest cumulative hospitalization rates for influenza B were among children younger than five years (n=37 per 100,000 population) and children between the ages of 5-19 years (n=15 per 100,000 population). Continued vigilance and surveillance around influenza B trends and epidemiology is required to contribute to effective epidemic preparedness.