Traditional Adjuvants Research Articles

Biogenic silver nanoparticle as an adjuvant in an S1 subunit recombinant vaccine.

Adjuvants are crucial for maintaining specific, protective, and long-lasting immunity. Here, we aimed to evaluate the antigenic and immunogenic activity of a recombinant form of the S1 domain of the Spike protein, associated with biogenic silver nanoparticles (bio-AgNP) and Alhydrogel® as an alternative and conventional adjuvant, respectively, for a SARS-CoV-2 subunit vaccine. We produced and evaluated the antigenicity of the recombinant S1 (rS1) protein by testing its recognition by antibodies present in SARS-CoV-2 positive human serum. The immunogenicity of the rS1 protein was assessed in vivo by its ability to induce antibody production in mice. Furthermore, we sought to establish the types of humoral and cellular immune responses generated through intramuscular immunization in BALB/c mice with the rS1 + bio-AgNP vaccine. The recombinant S1 (rS1) protein was successfully cloned, expressed in Escherichia coli, and confirmed to have strong antigenic potential, being recognized by human antibodies up to a 1:51,200 serum dilution. In vivo assays showed that vaccines using rS1 with either bio-AgNP or Alhydrogel® as adjuvants induced high and consistent antibody titers (1:51,200) and a range of antibody isotypes in mice. Cellular immune response analysis revealed significant IL-10 expression with rS1 + bio-AgNP and both IL-10 and TNFα expression with rS1 + Alhydrogel®. These results support rS1 + bio-AgNP as a promising vaccine candidate for future development, highlighting its potential not only as a viable alternative to traditional adjuvants but also as an innovative contribution to advancing more effective and accessible immunological strategies.

Development of a New Vaccine Adjuvant System Based on the Combination of the Synthetic TLR4 Agonist FP20 and a Synthetic QS-21 Variant.

In this study, we formulated an alternative to AS01b by combining FP20, a synthetic TLR4 agonist, and QS21v, a minimal saponin adjuvant, aiming to improve the vaccine efficacy and stability. The phase transition temperature of FP20 was determined by using differential scanning calorimetry to be 43.9 °C, providing a foundation for the formulation process. The coformulation was prepared using a dry film method for even adjuvant distribution. Characterization by dynamic light scattering and nanoparticle tracking analysis revealed a uniform particle size distribution of ∼120 nm. Cryogenic electron microscopy (CryoEM) revealed nanosized interactions between FP20 and QS21v, forming stable structures that likely enhanced the antigen presentation and immune activation. These physicochemical properties contributed to a robust in vivo synergy, where the coformulation elicited significantly higher antigen-specific antibody titers compared to individual adjuvants. These findings suggest that the FP20+QS21v coformulation provides a potent, stable, and safer alternative to traditional adjuvants, enhancing both vaccine efficacy and immunogenicity.

Enhancing the Deformability of the Adjuvant: Achieving Lymph Node Targeted Delivery to Elicit a Long-Lasting Immune Protection.

A key challenge in vaccine development is to inducean effective and durable immune response. Live virus vaccines induce lifelong antibody responses; however, the immune responses induced by inactivated or subunit vaccines decrease gradually. Activation of the germinal center (GC) reaction, which generates long-lived plasma cells (LLPCs), is a key mediator of long-term antibody responses. To enhance the activation of GC, lymph node-targeted delivery of the vaccine is promoted by enhancing the deformability of the delivery vector. In this study, a double emulsion is designed with strong deformability and containing chitosan nanoparticles (CSNP) in the internal aqueous phase (WNP) for efficient antigen loading, called WNP/O/W. The flexible oil layer and the internally loaded positively charged particles endow the emulsion with strong deformability, continuously enrich model antigen ovalbumin(OVA)in the lymph nodes, activate germinal center B (GC B) cells and T follicular helper (TFH) cells, induce LLPCs, and obtain high-level antibody persistence for more than 5 months, which is significantly better than the traditional oil emulsion adjuvant. Concurrently, it also improves the immune-protective effect in aged mice. Altogether, these results indicate that WNP/O/W achieves lymph node targeted delivery by strengthening deformability, generating high-intensity antibody responses, and long-lasting immune protection.

Nanoparticle containing recombinant excretory/secretory-24 protein of Haemonchus contortus enhanced the cellular immune responses in mice.

Haemonchus contortus poses a global challenge as a parasite affecting small ruminants, yet the problem of absence of an effective vaccine against H. contortus infection still exists. This investigation sought to appraise the immunological reaction induced by recombinant H. contortus excretory/secretory-24 (rHcES-24) in combination with complete Freund's adjuvant (CFA) and bio-polymeric nanoparticles (NPs) within a murine model. In this study, rHcES-24 was encapsulated in poly(d, l-lactide-co-glycolide) (PLGA) and chitosan (CS) NPs, administered subcutaneously to mice. Researchers analyzed the NPs using scanning electron microscope (SEM) and assessed lymphocyte proliferation, specific antibodies, cytokines, T cell proliferation (CD3e+CD4+, CD3e+CD8a+), and phenotypic alteration in splenocytes (CD11c+CD83+, CD11c+CD86+) through flow cytometry to understand the immune response. The results demonstrated that the administration of nanovaccines (NVs) prompted immune responses towards Th1 pathway. This was indicated by notable enhancements in the production of specific antibodies, heightened cytokine levels, and a robust proliferation of lymphocytes observed in mice that received the NVs compared to control groups. Remarkably, mice vaccinated with the antigen-loaded NPs formulations exhibited considerably higher proportions of splenic dendritic cells (DCs) and T cells in comparison to those receiving the traditional adjuvant or the control groups. Incorporating HcES-24 protein into NPs effectively conferred immunity against H. contortus, paving the way for developing a targeted and commercial vaccine.

Basic Properties and Development Status of Aluminum Adjuvants Used for Vaccines.

Aluminum adjuvants, renowned for their safety and efficacy, act as excellent adsorbents and vaccine immunogen enhancers, significantly contributing to innate, endogenous, and humoral immunity. An ideal adjuvant not only boosts the immune response but also ensures optimal protective immunity. Aluminum adjuvants are the most widely used vaccine adjuvants and have played a crucial role in both the prevention of existing diseases and the development of new vaccines. With the increasing emergence of new vaccines, traditional immune adjuvants are continually being researched and upgraded. The future of vaccine development lies in the exploration and integration of novel adjuvant technologies that surpass the capabilities of traditional aluminum adjuvants. One promising direction is the incorporation of nanoparticles, which offer precise delivery and controlled release of antigens, thereby enhancing the overall immune response. This review summarizes the types, mechanisms, manufacturers, patents, advantages, disadvantages, and future prospects of aluminum adjuvants. Although aluminum adjuvants have certain limitations, their contribution to enhancing vaccine immunity is significant and cannot be ignored. Future research should continue to explore their mechanisms of action and address potential adverse reactions to achieve improved vaccine efficacy.

Smart nanoscale lamellated supramolecular assemblies overcome biofilm barriers and enhance foliar affinity for efficient control of bacterial diseases

Agricultural infections arising from morbigenous biofilms and biofilm-dispersed bacteria have become a huge obstacle, threatening global food supply and security. Recalcitrant dense biofilms assist the embedded pathogens to efficaciously evade the host immune responses and bactericidal attack, thereby causing inferior antibacterial efficacy and severe bacterial resistance. However, currently available bactericides don’t proclaim any competencies in inhibiting or eliminating intractable biofilms. Facing this daunting challenge, here, we have developed nanoscale lamellated supramolecular assemblies (PtA22@β-CD) integrated by a bioactive isopropanolamine-modified thiophenol (PtA22) and β-cyclodextrin (β-CD). These smart lamellar materials exhibit multipurpose orientations: (1) Strongly damaging mature biofilms of Xanthomonas citri (Xac) with a higher eradication rate of 91.9 % at 25 μg mL−1, after aged Xac for 24 h; (2) Killing biofilm-enclosed pathogenic bacteria that markedly reduces colony-forming units by 87.3 % at 25 μg mL−1; (3) Significantly weakening the biofilm-involved pathogenicity; (4) Enhancing foliar adhesion and deposition of PtA22@β-CD droplets. More attractively, in vivo pot experiments, PtA22@β-CD displayed excellent control efficiencies (protection 81.4 %, remediation 69.4 %, low-dose: 200 μg mL−1) against citrus bacterial canker, markedly overtopping the commercial thiodiazole-copper. Besides, PtA22@β-CD demonstrates broad-spectrum bioactivities against Xanthomonas oryzicola. This study is bright for enhancing agrochemical bioavailability and circumventing the large-scale use of hazardous traditional adjuvants.

Proanthocyanidins-based adjuvant for enhanced immune responses of SARS-CoV-2 subunit vaccine

Aluminum-containing adjuvants have been widely used in human vaccines, such as anti-COVID-19 vaccine, to enhance antigen-specific immune responses. However, a major limitation of aluminum adjuvants in clinical application is that they typically enhance humoral immune responses but have weaker effects on cellular immune responses. Therefore, there has been a continuous and active pursuit of novel adjuvants that can address the shortcomings of traditional adjuvants and improve vaccine efficacy. In this paper, we proposed a novel vaccine-adjuvant system utilizing the convenient physical mixing of natural proanthocyanidins (PCs) and its derivative with a recombinant RBD subunit vaccine, which induced comparable humoral immune responses compared to aluminum adjuvant. In the context of cellular immunity, PCs modified with 4-bromomethyl phenylboronic acid not only enhanced the maturation and migration of dendritic cells but also improved the antigen uptake and presentation capacity of monocytes, leading to robust activation of immune cells, particularly involving CD4+ and CD8+ T cells, thereby demonstrating a clear Th1/CTL response bias. In general, PCs andtheir derivatives could be potential innovative natural adjuvants which effectively balance the Th1/Th2 immune response to recompense for the deficiency of aluminum adjuvant, and our study also offers an approach to discovering safe and efficient natural adjuvants.

Poria cocos polysaccharide-loaded Alum Pickering emulsion as vaccine adjuvant to enhance immune responses

Traditional Alum adjuvants mainly elicit a Th2 humoral immune response, but fail to generate a robust Th1 cellular immune response. However, the cellular immune response is essential for vaccination against cancer and a number of chronic infectious diseases, including human immunodeficiency virus infection and tuberculosis. In our previous study, we demonstrated that the polysaccharide from Poria cocos (PCP) has the potential to serve as an immunologic stimulant, enhancing both humoral and cellular immune responses. However, this effect was only observed at high concentrations. In this study, to enhance the immune-stimulation effect of PCP and modify the type of immune response elicited by Alum adjuvant, we successfully developed a Pickering emulsion delivery system (PCP-Al-Pickering) using PCP-loaded Alhydrogel particles as the stabilizer. After optimization, the Pickering emulsion exhibited excellent storage capacity and effectively adsorbed the PCP and antigen. As an adjuvant delivery system, the PCP-Al-Pickering emulsion facilitated the antigen uptake by macrophages, increased the recruitment of cells at injection sites, improved the activation of dendritic cells in draining lymph nodes, elicited a potent and durable antibody response, and promoted the activation of CD4+ and CD8+ T cells. Importantly, the PCP-Al-Pickering emulsion adjuvant elicited a balanced Th1 and Th2 immune response, in comparison to Alum adjuvant. The PCP-Al-Pickering emulsion may serve as a safe and promising adjuvant delivery system to enhance immune responses.

Intra-lymph node crosslinking of antigen-bearing polymers enhances humoral immunity and dendritic cell activation.

Lymph node (LN)-resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen-presenting capabilities and proximity to a high concentration of immune cells. Direct intra-LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs. Herein, we describe a novel vaccination platform in which two complementary multi-arm poly(ethylene glycol) (PEG) polymers-one covalently bound to the model antigen ovalbumin (OVA)-are injected subcutaneously into two distinct sites. These materials then drain to the same LN through different lymphatic vessels and, upon meeting in the LN, rapidly crosslink. This system improves OVA delivery to, and residence time within, the draining LN compared to all control groups. The crosslinking of the two PEG components also improves humoral immunity without the need for any pathogen-mimicking adjuvants. Further, we observed a significant increase in non-B/T lymphocytes in LNs cross-presenting the OVA peptide SIINFEKL on MHC I over a dose-matched control containing alum, the most common clinical adjuvant, as well as an increase in DC activation in the LN. These data suggest that this platform can be used to deliver antigens to LN-resident immune cells to produce a stronger humoral and cellular immune response over materials-matched controls without the use of traditional adjuvants.

Development of α-Tocopherol Loaded PLGA Nanoparticles and Its Evaluation as a Novel Immune Adjuvant.

With the continuous development of preventive and therapeutic vaccines, traditional adjuvants cannot provide sufficient immune efficacy and it is of high necessity to develop safe and effective novel nanoparticle-based vaccine adjuvants. α-Tocopherol (TOC) is commonly used in oil-emulsion adjuvant systems as an immune enhancer, yet its bioavailability is limited by poor water solubility. This study aims to develop TOC-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TOC-PLGA NPs) to explore the potential of TOC-PLGA NPs as a novel nanoparticle-immune adjuvant. TOC-PLGA NPs are prepared by a nanoprecipitation method and their physicochemical properties are characterized. It is shown that TOC-PLGA NPs are 110.8nm, polydispersity indexvalue of 0.042, and Zeta potential of -13.26mV. The encapsulation efficiency and drug loading of NPs are 82.57% and 11.80%, respectively, and the cumulative release after 35days of in vitro testing reaches 47%. Furthermore, TOC-PLGA NPs demonstrate a superior promotion effect on RAW 264.7 cell proliferation compared to PLGA NPs, being well phagocytosed and also promoting antigen uptake by macrophages. TOC-PLGA NPs can strongly upregulate the expression of co-stimulatory surface molecules and the secretion of cytokines. In conclusion, TOC-PLGA NPs can be a novel vaccine adjuvant with excellent biocompatibility and significant immune-enhancing activity.

DNA programmed Mg-Al layered double hydroxide-based bi-adjuvant nanovaccines

Implementation of adjuvants is a requirement for inducing antigen-specific immune responses against infectious diseases. The conventional aluminum adjuvants used in clinical trials suffer from insufficient cellular immune response. Herein, we develop a bi-adjuvant nanovaccine containing receptor-binding domain (RBD) as antigen and DNA programmed Mg/Al layered double hydroxide (Mg/Al-LDH) as adjuvants, and thus achieve co-activation of potent humoral and cellular immune responses. The Mg/Al-LDH consisting of positively charged layers is firstly employed as scaffold to adsorb antigen via electrostatic interaction, and then CpG and dendritic cell (DC)-targeting aptamers co-encoded ultra-long DNA chains are easily decorated on the Mg/Al-LDH via interfacial assembly. The nanoscale formulations and interfacial targeting aptamers of nanovaccine facilitate their endocytosis by DC cells; the Mg/Al-LDH structure is acid-responsive and ensures the Al ions-inducing antigen cross-presentation for durable generation of antibody (Th2 immune response); and the agonist CpG in DNA chains can bind to the Toll-like receptor 9 (TLR 9) to activate cellular immunity (Th1 immune response). The bi-adjuvant nanovaccine fully combines the advantages of nanosheet alum-like adjuvant and precisely customization of DNA, and thus balances the Th1/Th2 immune response for compensating the deficiency of traditional alum adjuvant, providing a design guidance for creating next-generation of safe and efficient adjuvants in immunology.

Unfolding Protein-Based Hapten Coupling via Thiol-Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants.

Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol-maleimide "click" chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine-BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

Photothermal-enhanced in situ supramolecular hydrogel promotes bacteria-infected wound healing in diabetes.

Bacterial infection can impede the healing of chronic wounds, particularly diabetic wounds. The high-sugar environment of diabetic wounds creates a favorable condition for bacterial growth, posing a challenge to wound healing. In clinical treatment, the irregular shape of the wound and the poor mechanical properties of traditional gel adjuvants make them susceptible to mechanical shear and compression, leading to morphological changes and fractures, and difficult to adapt to irregular wounds. Traditional gel adjuvants are prepared in advance, while in situ gel is formed at the site of administration after drug delivery in a liquid state, which can better fit the shape of the wound. Therefore, this study developed an in situ HA/GCA/Fe2+-GOx gel using a photothermal-enhanced Fenton reaction to promote the generation of hydroxyl radicals (·OH). The generation of ·OH has an antibacterial effect while promoting the formation of the gel, achieving a dual effect. The addition of double-bonded adamantane (Ada) interacts with the host-guest effect of graphene oxide and the double-bond polymerization of HAMA gel, making the entire gel system more complete. At the same time, the storage modulus (G') of the gel increased from 130 to 330Pa, enhancing the mechanical properties of the gel. This enables the gel to have better injectability and self-healing effects. The addition of GOx can consume glucose at the wound site, providing a good microenvironment for the repair of diabetic wounds. The gel has good biocompatibility and in a diabetic rat wound model infected with S. aureus, it can effectively kill bacteria at the wound site and promote wound repair. Meanwhile, the inflammation of wounds treated with HA/GCA/Fe2+-GOx+NIR was lighter compared to untreated wounds. Therefore, this study provides a promising strategy for treating bacterial-infected diabetic wounds.

Aluminum hydroxide nanoparticle adjuvants can reduce the inflammatory response more efficiently in a mouse model of allergic asthma than traditional aluminum hydroxide adjuvants.

Traditional aluminum hydroxide is widely used as a vaccine adjuvant. Despite its favorable safety profile, it can cause an inflammatory response at the injection sites. However, multiple studies have shown that aluminum hydroxide nanoparticles have more potent adjuvant activity than their traditional aluminum hydroxide counterparts as antigen carriers; it has also been found that the local inflammation caused by aluminum hydroxide nanoparticle adjuvants is milder than that of other adjuvants. The aim of the present study was to compare the degree of inflammatory response between the aluminum hydroxide nanoparticle adjuvants and the traditional aluminum hydroxide adjuvants in the desensitization treatment of a mouse model of house dust mite (HDM)-induced allergic asthma. Mice were sensitized intraperitoneally with HDM. Subcutaneous desensitization was performed with PBS, traditional aluminum hydroxide adjuvants and aluminum hydroxide nanoparticle adjuvants. The mice were challenged and subsequently euthanized. The skin tissue at the local injection sites was assessed and specific indices were measured, such as the response of specific immunoglobulins, the airway hyper-responsiveness (AHR), and the inflammation in the bronchoalveolar lavage and lung tissues. Early hypersensitivity responses were suppressed in mice treated with subcutaneous immunotherapy (SCIT). Both traditional aluminum hydroxide-SCIT and aluminum hydroxide nanoparticle-SCIT could inhibit AHR. However, aluminum hydroxide nanoparticle-SCIT was able to significantly inhibit the secretion of eosinophils in the lung tissue and the production of type 2 cytokine Interleukin (IL)-5 in blood compared with the corresponding effects noted by traditional aluminum hydroxide adjuvants. Moreover, the aluminum hydroxide nanoparticle group reduced the inflammatory response at the local injection site. Collectively, the data indicated that allergen-specific immunotherapy using aluminum hydroxide nanoparticle adjuvants reduces lung and local inflammation compared with traditional aluminum hydroxide adjuvants.

Salmonella enterica serovar Choleraesuis vector outperforms alum as an adjuvant, increasing a cross-protective immune response against Glaesserella parasuis

The adjuvant and/or vector significantly affect a vaccine's efficacy. Although traditional adjuvants such as alum have contributed to vaccine development, deficiencies in the induction of cellular and mucosal immunity have limited their further promotion. Salmonella vectors have unique advantages for establishing cellular and mucosal immunity due to mucosal pathways of invasion and intracellular parasitism. In addition, Salmonella vectors can activate multiple innate immune pathways, thereby promoting adaptive immune responses. In this work, the attenuated Salmonella enterica serovar Choleraesuis (S. Choleraesuis) vector rSC0016 was used to deliver the conserved protective antigen HPS_06257 of Glaesserella parasuis (G. parasuis), generating a novel recombinant strain rSC0016(pS-HPS_06257). The rSC0016(pS-HPS_06257) can express and deliver the HPS_06257 protein to the lymphatic system of the host. In comparison to HPS_06257 adjuvanted with alum, rSC0016(pS-HPS_06257) significantly increased TLR4 and TLR5 activation in mice as well as the levels of proinflammatory cytokines. In addition, rSC0016 promoted a greater degree of maturation in bone marrow-derived dendritic cells (BMDCs) than alum. The specific humoral, mucosal, and cellular immune responses against HPS_06257 in mice immunized with rSC0016(pS-HPS_06257) were significantly higher than those of HPS_06257 adjuvanted with alum. HPS_06257 delivered by the S. Choleraesuis vector induces a Th1-biased Th1/Th2 mixed immune response, while HPS adjuvanted with alum can only induce a Th2-biased immune response. HPS_06257 adjuvanted with alum only causes opsonophagocytic activity (OPA) responses against a homologous strain (G. parasuis serotype 5, GPS5), whereas rSC0016(pS-HPS_06257) could generate cross-OPA responses against a homologous strain and a heterologous strain (G. parasuis serotype 12, GPS12). Ultimately, HPS_06257 adjuvanted with alum protected mice against lethal doses of GPS5 challenge by 60 % but failed to protect mice against lethal doses of GPS12. In contrast, mice immunized with rSC0016(pS-HPS_06257) had 100 % or 80 % survival when challenged with lethal doses of GPS5 or GPS12, respectively. Altogether, the S. Choleraesuis vector rSC0016 could potentially generate an improved innate immune response and an improved adaptive immunological response compared to the traditional alum adjuvant, offering a novel concept for the development of a universal G. parasuis vaccine.

Advances in Helicobacter pylori vaccine research: From candidate antigens to adjuvants-A review.

Helicobacter pylori is a Gram-negative, spiral-shaped bacterium that infects approximately 50% of the world's population and has been strongly associated with chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoma, and gastric cancer. The elimination of H. pylori is currently considered one of the most effective strategies for the treatment of gastric-related diseases, so antibiotic therapy is the most commonly used regimen for the treatment of H. pylori infection. Although this therapy has some positive effects, antibiotic resistance has become another clinically prominent problem. Therefore, the development of a safe and efficient vaccine has become an important measure to prevent H. pylori infection. PubMed and ClinicalTrials.gov were systematically searched from January 1980 to March 2023 with search terms-H. pylori vaccine, adjuvants, immunization, pathogenesis, and H. pylori eradication in the title and/or abstract of literature. A total of 5182 documents were obtained. Based on the principles of academic reliability, authority, nearly publicated, and excluded the similar documents, finally, 75 documents were selected, organized, and analyzed. Most of the candidate antigens used as H. pylori vaccines in these literatures are whole-cell antigens and virulence antigens such as UreB, VacA, CagA, and HspA, and the main types of vaccines for H. pylori are whole bacteria vaccines, vector vaccines, subunit vaccines, nucleic acid vaccines, epitope vaccines, etc. Some vaccines have shown good immune protection in animal trials; however, few vaccines show good in clinical trials. The only H. pylori vaccine passed phase 3 clinical trial is a recombinant subunit vaccine using Urease subunit B (UreB) as the vaccine antigen, and it shows good prophylactic effects. Meanwhile, the adjuvant system for vaccines against this bacterium has been developed considerably. In addition to the traditional mucosal adjuvants such as cholera toxin (CT) and E. coli heat labile enterotoxin (LT), there are also promising safer and more effective mucosal adjuvants. All these advances made safe and effective H. pylori vaccines come into service as early as possible. This review briefly summarized the advances of H. pylori vaccines from two aspects, candidates of antigens and adjuvants, to provide references for the development of vaccine against this bacterium. We also present our prospects of exosomal vaccines in H. pylori vaccine research, in the hope of inspiring future researchers.

Calcium phosphate nanoparticles conjugated with outer membrane vesicle of Riemerella anatipestifer for vaccine development in ducklings

Biodegradable calcium phosphate nanoparticles offer a viable substitute for traditional adjuvants such as aluminum in vaccine production. Calcium phosphate nanoparticle adjuvanted with outer membrane vesicle (OMV) of gram negative bacteria may induce efficient immune response in the host. The present study was carried out to evaluate the potential of a mucosal vaccine formulation of calcium phosphate (CAP) nanoparticle using OMV of Riemerella anatipestifer (RA) as antigen against New Duck disease in ducks. The work was initiated with isolation, identification of RA, followed by OMV production and extraction. The CAP-OMV nanoparticle was prepared and characterized. The efficacy of the vaccine formulation and toxicity were studied in ducks. The average OMV yield in terms of protein concentration was found to be 122.33 ± 3.48 mg per liter of BHI broth. In SDS-PAGE, isolated OMVs exhibited presence of 16 distinct protein bands with molecular weight ranging from 142.1 to 12.1 kDa. Seven protein bands of 74.1, 69.3, 55.5, 50.6, 45.6, 25.1 and 13.1 kDa were detected relatively more distinct. The major bands detected in our findings were 42 kDa, 37 kDa and 16 kDa that corresponds to OmpA, OmpH, P6 respectively. The mean zeta size (±SD) and potential of the nanoparticle were 246.20 ± 0.53 nm and −25.60 ± 5.97 respectively. In transmission electron microscopy (TEM), the nanoparticles exhibited an average diameter of 129.80 ± 11.10 nm and displayed spherical morphology. The median protective dose (PD50) of CAP-OMV nanoparticle was 1881.10 μg of protein. Group I ducks received 3762 μg of protein (entrapped protein in CAP-OMV nanoparticle) via intra nasal route and it showed the highest serum IgG and secretory IgA level than other immunized groups. All experimental ducks were challenged with 10 × LD50 on 35 days of post primary immunization. Group I showed 100 % survivability in the challenge study. No gross and biochemical indication of acute or chronic toxicity were recorded. In conclusion, our results suggest that CAP-OMV nanoparticle can be a safe and efficient mucosal vaccine delivery system for RA, eliciting strong immune response in the host.

Advancements in Vaccine Adjuvants: The Journey from Alum to Nano Formulations.

Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in reputable databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. The goal of this review is to provide a thorough analysis of the advances in the field of adjuvant research, to trace the evolution, and to understand the effects of the various adjuvants. Historically, alum was the pioneer in the field of adjuvants because it was the first to be approved for use in humans. It served as the foundation for subsequent research and innovation in the field. As science progressed, research shifted to identifying and exploiting the potential of newer adjuvants. One important area of interest is nano formulations. These advanced adjuvants have special properties that can be tailored to enhance the immune response to vaccines. The transition from traditional alum-based adjuvants to nano formulations is indicative of the dynamism and potential of vaccine research. Innovations in adjuvant research, particularly the development of nano formulations, are a promising step toward improving vaccine efficacy and safety. These advances have the potential to redefine the boundaries of vaccination and potentially expand the range of diseases that can be addressed with this approach. There is an optimistic view of the future in which improved vaccine formulations will contribute significantly to improving global health outcomes.

Synthesis and Optimization of Next-Generation Low-Molecular-Weight Pentablock Copolymer Nanoadjuvants.

Polymeric nanomaterials such as Pluronic®-based pentablock copolymers offer important advantages over traditional vaccine adjuvants and have been increasingly investigated in an effort to develop more efficacious vaccines. Previous work with Pluronic® F127-based pentablock copolymers, functionalized with poly(diethyl aminoethyl methacrylate) (PDEAEM) blocks, demonstrated adjuvant capabilities through the antigen presentation and crosslinking of B cell receptors. In this work, we describe the synthesis and optimization of a new family of low-molecular-weight Pluronic®-based pentablock copolymer nanoadjuvants with high biocompatibility and improved adjuvanticity at low doses. We synthesized low-molecular-weight Pluronic® P123-based pentablock copolymers with PDEAEM blocks and investigated the relationship between polymer concentration, micellar size, and zeta potential, and measured the release kinetics of a model antigen, ovalbumin, from these nanomaterials. The Pluronic® P123-based pentablock copolymer nanoadjuvants showed higher biocompatibility than the first-generation Pluronic® F127-based pentablock copolymer nanoadjuvants. We assessed the adjuvant capabilities of the ovalbumin-containing Pluronic® P123-based pentablock copolymer-based nanovaccines in mice, and showed that animals immunized with these nanovaccines elicited high antibody titers, even when used at significantly reduced doses compared to Pluronic® F127-based pentablock copolymers. Collectively, these studies demonstrate the synthesis, self-assembly, biocompatibility, and adjuvant properties of a new family of low-molecular-weight Pluronic® P123-based pentablock copolymer nanomaterials, with the added benefits of more efficient renal clearance, high biocompatibility, and enhanced adjuvanticity at low polymer concentrations.

The emergence of nanovaccines as a new paradigm in virological vaccinology: a review

Vaccination has made an enormous contribution to global health. Treatment resistance for infectious diseases is growing quickly, and chemotherapeutic toxicity in cancer means that vaccines must be made right away to save humanity. But subunit vaccinations alone don’t give enough strong and long-lasting protection against infections that can kill. Nanoparticle (NP)-based delivery vehicles, such as dendrimers, liposomes, micelles, virosomes, nanogels, and microemulsions, offer interesting ways to get around the problems with traditional vaccine adjuvants. The nanovaccines (50–250 nm in size) are most efficient in terms of tissue targeting, staying in the bloodstream for a long time. Nanovaccines can improve antigen presentation, targeted delivery, stimulation of the body’s innate immune system, and a strong T-cell response without putting people at risk. This can help fight infectious diseases and cancers. Also, nanovaccines can be very helpful for making cancer treatments that use immunotherapy. So, this review highlights the various types of NPs used in the techniques that have worked in the new paradigm in viral vaccinology for infectious diseases. It gives a full rundown of the current NP-based vaccines, their potential as adjuvants, and the ways they can be delivered to cells. In the future, the best nanovaccines will try to be more logically designed, have more antigens in them, be fully functionalized, and be given to the right people.