Injection Of Vaccine Research Articles

LADS: a powerful vaccine platform for cancer immunotherapy and prevention

BackgroundThe intracellular bacterium Listeria monocytogenes is an attractive vector for cancer immunotherapy as it can effectively deliver tumor antigens to antigen-presenting cells, leading to a robust antitumor response.ResultsIn this study, we developed a novel vaccine platform called Listeria-based Live Attenuated Double Substitution (LADS), which involves introducing two amino acid substitutions (N478AV479A) into the virulence factor listeriolysin O (LLO). LADS is a safe vaccine platform, with an attenuation of nearly 7000-fold, while retaining complete immunogenicity due to the absence of deletion of any virulence factors. We developed two LADS-based vaccines, LADS-E7 and LADS-AH1, which deliver the human papillomavirus (HPV) type 16 E7 oncoprotein and murine colon carcinoma immunodominant antigen AH1, respectively. Treatment with LADS-E7 or LADS-AH1 significantly inhibited and regressed established tumors, while also dramatically increasing the populations of tumor-infiltrated antigen-specific CD8+ T cells. RNA-sequencing analysis of tumor tissue samples revealed that LADS-E7 altered the expression of genes related to the immune response. Moreover, intratumoral injection of LADS-based vaccines induced strong antitumor responses, generating systemic antitumor responses to control distant tumor growth. Encouragingly, LADS-E7 or LADS-AH1 immunization effectively prevented tumor formation and growth.ConclusionsOur findings demonstrate that LADS-based vaccines represent a more powerful platform for the development of immunotherapeutic and preventive vaccines against cancers and infectious diseases.

Assessment of the immunity gap of two vaccination programs against Gumboro disease in Luong Phuong chicken

Maternal-derived antibody (MDA) is the priority protection against environmental Infectious Bursal Disease Virus (IBDV) in the first weeks. The passive immunity decreases, but the active immunity is not enough to protect chicks, so shortening the high-risk period is crucial to IBD control. The objective of this study was to evaluate the immunity gap between 2 vaccination programs against infectious bursal disease (IBD) in Luong Phuong chickens. A total of 34,600 chicks were administered by subcutaneous injection of IBD vaccine at 0.1 mL/dose at the hatchery. At 12 days old, 18,000 chicks were vaccinated with the M.B strain vaccine and 16,600 chicks were vaccinated with the 228E strain vaccine by drinking water. The IBD and Newcastle disease (ND) antibody evaluations were based on the Enzyme-linked immunosorbent assay (ELISA) technique. Parameters were recorded until slaughter including body weight, average daily gain, feed conversion rate, and mortality. The IBD MDA at 1 day old was medium and uniform (3809 and 45.3%), which could protect against IBD virus from 1 to 2 weeks old. At 28 days old, the IBD antibody titer of the MB vaccine was higher than that of the 228E vaccine, various proportions of samples in the M.B group exceeding 1,000 titers (40% vs. 0%), and it was a statistically significant difference (1,133 vs. 161) (P < 0.01). Besides, the M.B vaccine created a faster and stronger immune response than the 228E vaccine, shortening the immune gap and protecting chicks earlier. The humoral immune response to the ND vaccine was good, with no difference between 2 groups, which proved that the M.B virus did not cause immunosuppression. The production parameters of chickens between the 2 groups were the same. In summary, the M.B vaccine made a short immune gap and did not cause immunodeficiency in chickens.

Injectable and Degradable Zwitterionic Cryogels as Cancer Vaccine Platforms to Prevent Cancer Recurrence after Surgery.

Cancer has become a highly prevalent disease and poses serious threats to human health. Conventional cancer treatments still face high risks of recurrence. Training the immune system to recognize and eliminate tumors via external stimulation, such as vaccines, emerges as a promising approach for cancer prevention and treatment. However, injectable vaccines may have limited immune activation, causing difficulties in maintaining long-term immune surveillance of tumorigenesis by tumor-specific cytotoxic T cells. Here, degradable zwitterionic cryogels were prepared using the cryogelation technique. The cryogenic preparation maintained the biological activities of tumor antigens and immune adjuvants loaded in the cryogels. The macroporous structure endowed the injectability of cryogels into the body via conventional syringes. In the presence of proteases, the cryogels degraded, allowing sustained release of antigens and adjuvants, ensuring continued dendritic cell (DC) recruitment and antigen presentation to maturing tumor-specific cytotoxic T cells. In vivo experiments demonstrated that the cryogel cancer vaccines elicited robust immune activation and effectively modulated tumor microenvironments. The combination with photothermal therapy significantly inhibited tumor growth, showing great potential for preventing postoperative recurrence. Additionally, the zwitterionic cryogels were biocompatible without obvious toxicities during degradation. The cryogels could serve as effective vaccine platforms to prevent cancer recurrence after surgery.

CNSC-17. UPREGULATION OF CCL4 AFTER TREATMENT WITH A NOVEL MRNA VACCINE SHIFTS THE PHENOTYPE OF CCR5-EXPRESSING MICROGLIA WITHIN TUMOR MICROENVIRONMENT

Abstract INTRODUCTION Intra-tumoral immunosuppression is a major cause of treatment failure for patients with glioblastoma (GBM). Our group has developed a proprietary vaccine that combines mRNA encapsulated in lipid nanoparticles with PEG hydrogel and a chemokine (CXCL9). This hydrogel-chemokine-mRNA (HCM) vaccine is delivered subcutaneously (SQ) and results in significant anti-tumor efficacy in syngeneic murine glioma models. The objective of this study was to evaluate the effects of the vaccine on the tumor microenvironment (TME). METHODS C57BL/6 mice underwent intracranial implantation of KR158-luc tumor cells and underwent SQ injection of the HCM vaccine using total tumor mRNA. Tumors were collected for analysis at different time points. Q-PCR and flow cytometry were done to evaluate the differential gene expression and CCR5 expression (receptor for CCL4) in the TME following HCM vaccination. RESULTS CCL4 was found to be upregulated in tumor-bearing animals treated with HCM vaccine using PCR. In a separate experiment, CCL4 blockade was given prior to HCM vaccination and this resulted in abrogation of the survival benefit of the vaccine. Next, flow cytometry results revealed that microglia in the TME had the highest expression of the CCR5 receptor. Further, QPCR on the isolated microglia from TME revealed significant up-regulation of inflammatory gene CCL5 (25 fold) and down-regulation of anti-inflammatory genes as compared to untreated control and empty hydrogel control. CONCLUSION The HCM vaccine results in significant anti-tumor efficacy in murine syngeneic murine glioma which is dependent on upregulation of CCL4 in the TME. The CCL4 exerts its effect through microglia expressing CCR5 in the TME. HCM vaccination shifted the microglia phenotype from immune-suppression to inflammatory state. Further analysis of the effect of CCR5 knock out on the HCM vaccine survival efficacy are under current investigation.

Expanding Horizons: Increasing Injectable Vaccine in the Expanded Program on Immunization

The World Health Organization started the Expanded Program on Immunization in 1974, including 6 antigens with up to 8 vaccine doses for childhood vaccination. The number of antigens has now increased to 11 antigens in 21 vaccines. The expansion of vaccination programs to include more antigens and doses has led to concerns about the burden of multiple injections on infants and children, as well as factors such as fear of adverse reactions, pain, and overall acceptability of vaccines. To address these challenges, there's a call for research to focus on developing combined vaccines that can be administered through more acceptable routes, such as oral, nasal, or needleless administration. This approach could potentially reduce the number of injections required and increase the willingness of individuals to receive vaccines. We highlight the importance of ongoing research and innovation in vaccine development and delivery methods to ensure that vaccination programs remain effective, efficient, and acceptable to the communities they serve, particularly in resource-limited settings.

Local Inflammatory and Systemic Antibody Responses Initiated by a First Intradermal Administration of Autogenous Salmonella-Killed Vaccines and Their Components in Pullets

Vaccination strategies are used to manage Salmonella in chickens. Salmonella-killed vaccines are considered safer since they are inactivated. However, little is known regarding the cellular immune activities at the site of vaccine administration of Salmonella-killed vaccines. The growing feather (GF) cutaneous test has been shown to be an effective bioassay to monitor local tissue/cellular responses. We assessed local and systemic antibody responses initiated by intradermal injection of Salmonella-killed vaccines into GF-pulps of 14–15-week-old pullets. Treatments consisted of two autogenous Salmonella-killed vaccines (SV1 and SV2), S. Enteritidis (SE) lipopolysaccharide (SE-LPS), and the water-oil-water (WOW) emulsion vehicle. GF-pulps were collected before (0 h) and at 6, 24, 48, and 72 h post-GF-pulp injection for leukocyte population analysis, while heparinized blood samples were collected before (0 d) and at 3, 5, 7, 10, 14, 21, and 28 d after GF-pulp injections to assess plasma levels (a.u.) of SE-specific IgM, avian IgY (IgG), and IgA antibodies using an ELISA. Injection of GF-pulps with SV1, SV2, or SE-LPS, all in a WOW vehicle, initiated inflammatory responses characterized by the recruitment of heterophils, monocytes/macrophages, and a few lymphocytes. The WOW vehicle emulsion alone recruited more lymphocytes than vaccines or SE-LPS. The SV1 and SV2 vaccines stimulated Salmonella-specific IgM and IgA early, while IgG levels were greatly elevated later during the primary response. Overall, SV1 and SV2 stimulated a heterophil and macrophage-dominated local inflammatory- and SE-specific humoral response with an isotype switch from IgM to IgG, characteristic of a T-dependent primary antibody response. This study provides comprehensive information on innate and adaptive immune responses to autogenous Salmonella-killed vaccines and their components that will find application in the management of Salmonella in poultry.

Immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals: A randomized, parallel-controlled of homologous vaccine with different immune procedure study

ABSTRACT This study was a randomized, parallel-controlled of homologous vaccines with different immune procedure research to evaluate the immunogenicity and immune persistence of Zagreb 2-1-1 regimen of rabies vaccine in Chinese healthy individuals. 240 subjects aged ≤ 20、21-50、≥51 y were randomly divided into 2 groups (1:1), Zagreb 2-1-1 regimen receivers as experimental group and Essen 5 regimen receivers as controlled group. Researchers collected venous blood of each subject before vaccine injection and on the day 7, 14, 42, 180, 365 after first dose. The immunogenicity and immune persistence was assessed by neutralizing antibody. The positive rate of neutralizing antibody in experimental group was 14.53% on the 7th day, and raised to 100% on the 14th day. It showed no significant difference between experimental and controlled group (P>0.05). Either in experimental or controlled group, GMC of neutralizing antibody was up to the peak on the 14th day, and it showed no significant difference between two groups (P>0.05). On the 42nd day, the antibody positive rate remained 100% with both Zagreb 2-1-1 and Essen 5 regimens, and the GMC of antibodies also remained high level. Then, on the 180th and 365th day with both regimens, the GMC of antibodies dropped dramatically, although it remained above the protective level of 0.5 IU/ml, the positive rates dropped to 84.40% and 84.11% (on the 180th day), and 61.29% and 58.62% (on the 365th day). Rabies vaccine injected by Zagreb 2-1-1 regimen can produce neutralizing antibody fastly and perdurably. Registration: ClinicalTrials.gov #NCT01821911and NCT01827917

Enhancements in the expressions of genes associated with the immunity, muscle growth, and antioxidant activity of 14 d broilers in response to the in ovo injection of the Marek's disease vaccine alone or in conjunction with in ovo and dietary supplemental administration of 25-hydroxycholecalciferol

Influences the Marek's disease vaccine (MDV) alone or combined with the in ovo and dietary administration of 25-hydroxycholecalciferol (25OHD3) on the expression of genes associated with the breast muscle deposition, adaptive and innate immunity, and antioxidant and vitamin D activities of 14 d-old broilers were investigated. Four in ovo treatments were: non-injected; commercial MDV-alone-injected (50 μl); or 50 μl of MDV containing 1.2 (MDV+25OHD3-1.2) or 2.4 (MDV+25OHD3-2.4) μg of 25OHD3. Two dietary treatments were a commercial diet containing 25OHD3 (250 IU)/kg of feed (control) or the same diet supplemented with additional 25OHD3 (2,760 IU)/kg of feed (Hy-D diet). One bird per pen (48 total) was sampled at 14 d for determination of the expression of genes involved with the muscle deposition (MyoD1, MyoG, Pax3, and Mrf4), immunity (INF-γ, IL-10, IL-8, IL-1β, and TGF-β4), antioxidant capacity (SOD1, SOD2, GSH-P1, GSH-P7, and CAT), and vitamin D activity (VDR, 1α-hydroxylase, and 24-hydroxylase) in the spleen and pectoralis major (P.major) muscle. The treatment differences were considered significant at P ≤ 0.05. In the P. major, Mrf4 and MyoG were up-regulated in Hy-D-fed birds. Also, the in ovo and dietary 25OHD3 sources individually increased SOD2 gene expression in the P. major. In the spleen, the expressions of IL-1β and IL-8 were down-regulated and IL-10 and TGF-β4 gene expressions were up-regulated in Hy-D-fed birds than those commercial-fed broiler. In ovo and dietary 25OHD3 sources enhanced vitamin D gene (1α-hydroxylase and 24-hydroxylase) activities in the breast and spleen. In ovo x dietary treatment interactions were significant for the MyoD1, IL-8, Pax3, TGF-β4 genes of the P. major, in which the combined MDV with 1.2 μg of 25OHD3 enhanced their expressions in birds fed the Hy-D diet. In conclusion, both 25OHD3 sources promoted the expression of genes associated with immunity and P. major growth. It is recommended that both 25OHD3 sources can be used to promote the gene expression of 14-d-old broilers in the spleen and breast muscle when MDV administered in ovo.

Bilateral purtscher-like retinopathy associated with DRESS syndrome: a case report

BackgroundTo report a case of Bilateral Purtscher-like retinopathy associated with DRESS syndrome managed with ocular and systemic treatments.Case presentationA 29-year-old healthy female developed multi-organ (cutaneous, hematologic, renal and hepatic) disfunction and profound vision loss 1 month after Human papillomavirus vaccine injection. At the first presentation, her visual acuity was counting fingers in both eyes. Fundus exam showed remarkable cotton-wool spots, retinal hemorrhages and macular edema. She was diagnosed DRESS syndrome and Purtscher-like retinopathy and treated with intravitreal injection of ranibizumab, systemic steroids anticoagulants, and plasma exchange. The patient finally recovered from this life-threatening condition but left with permanent visual damage.ConclusionPurtscher-like retinopathy could be complicated by DRESS syndrome which is usually considered a type IV hypersensitivity reaction.

Vaccines efficacy against infection with circulating feline calicivirus after one single injection: Comparison of Leucofeligen™ FeLV/RCP and Purevax™ RCPFeLV vaccines

Feline calicivirus (FCV) is a worldwide pathogen that affects the general health status of cats. The aim of this study was to assess the efficacy of the FCV component of two multivalent commercial vaccines after one injection. The cats assigned to the vaccinated groups received one subcutaneous injection of either the Leucofeligen™ FeLV/RCP (Virbac, France) vaccine or the Purevax™ RCPFeLV (Boehringer Ingelheim, Germany) vaccine. In the control group, the cats did not receive any vaccine. Three weeks after the vaccine injection, all the cats were inoculated with a heterologous calicivirus strain, isolated in the field. The clinical signs of calicivirosis and the viral shedding were assessed. The results demonstrated that Leucofeligen™ FeLV/RCP could protect kittens against FCV infection by reducing clinical signs and viral excretion from 3 weeks after the first injection of primary vaccination, whereas Purevax™ RCPFeLV couldn't offer the same level of protection in similar experimental conditions.

Research Note: The infectious bursal disease (Gumboro disease) vaccination scheme affects the quantitative and qualitative carcass characteristics and the immune response of Ross 308 broiler chickens

After different vaccinations, the study aimed to assess carcass composition, meat quality, and the level of the infectious bursal disease antibody titers in broiler chickens. In the experiment, 4 (30 chicks per group, 120 total) groups of Ross 308 broiler chickens (males and females) were included. Then, they were vaccinated at the hatchery. Group I was immunized against infectious avian bronchitis (IB) and Newcastle disease (ND) using vaccine A (20 mL/100 birds) and vaccine B (20 mL/100 birds), respectively, with injectable vaccine C (0.2 mL/each) targeting Infectious bursal' and Marek's diseases (MD). Group II received the same vaccinations for IB and ND, with separate injectable D vaccines for MD (0.2 mL/unit) and E for infectious bursal' disease (0.2 mL/each). Group III was similarly vaccinated for IB and ND; however, they received only vaccine D (0.2 mL/each) for MD, and on d 23, vaccine F was administered via drinking water against Gumboro disease (0.05 mL/each). Group IV served as the control and was not vaccinated. Ten carcasses from each group on d 42 were taken for carcass composition analysis and meat quality, including pH, color, and water-holding capacity (WHC). During rearing, on d 14, 28, and 42, blood was collected to determine the level of antibodies against infectious bursal' disease. Additionally, hematocrit (HCT), hemoglobin (HGB), and red blood cells were analyzed. In group I, a higher bursa of Fabricius weight than in the other groups was found (P < 0.001), and the liver weight was lower compared to group II (P = 0.020). In breast muscle, the pH24 was higher in the control group than in group I (P = 0.036). Lightness (L*) in breast and leg muscles from group I was higher than in group II (P < 0.05). WHC was higher in group I than in group II (P = 0.025). The antibody titers of infectious bursal' disease was higher in group I on d 28 than in other groups (P < 0.05). Vaccine C (1 dose 0.2 mL/1 bird) of the reconstituted vaccine with the live recombinant virus strain vHVT013-69, not less than 3.6 - 5.0 log10 PFU) had a beneficial effect.

Duckweeds as edible vaccines in the animal farming industry.

Animal diseases are among the most debilitating issues in the animal farming industry, resulting in decreased productivity and product quality worldwide. An emerging alternative to conventional injectable vaccines is edible vaccines, which promise increased delivery efficiency while maintaining vaccine effectiveness. One of the most promising platforms for edible vaccines is duckweeds, due to their high growth rate, ease of transformation, and excellent nutritional content. This review explores the potential, feasibility, and advantages of using duckweeds as platforms for edible vaccines. Duckweeds have proven to be superb feed sources, as evidenced by numerous improvements in both quantity (e.g., weight gain) and quality (e.g., yolk pigmentation). In terms of heterologous protein production, duckweeds, being plants, are capable of expressing proteins with complex structures and post-translational modifications. Research efforts have focused on the development of duckweed-based edible vaccines, including those against avian influenza, tuberculosis, Newcastle disease, and mastitis, among others. As with any emerging technology, the development of duckweeds as a platform for edible vaccines is still in its early stages compared to well-established injectable vaccines. It is evident that more proof-of-concept studies are required to bring edible vaccines closer to the current standards of conventional vaccines. Specifically, the duckweed expression system needs further development in areas such as yield and growth rate, especially when compared to bacterial and mammalian expression systems. Continued efforts in this field could lead to breakthroughs that significantly improve the resilience of the animal farming industry against disease threats.

Liposome-encapsulated dextrazide modifies spleen extracellular matrix composition in mice with chronic BCG-induced inflammation

Fibrosis of parenchymal organs is a common complication of tuberculosis. In a model of BCG-induced inflammation in mice, changes in the metabolism of the extracellular matrix (ECM) of the spleen were demonstrated with the introduction of a liposome-encapsulated dextrazide (LEDZ) containing isoniazid and oxidized dextran.The mice were divided into 4 groups: 1 – intact animals; 2 – infected mice after a single intravenous injection of BCG vaccine. 6 mo after infection, a solution of LEDZ was administered intraperitoneally to mice of group 3 for 3 mo, and inhaled to mice of group 4. Group 2 mice showed the signs of pronounced spleen fibrosis (increased content of hyaluronan, hydroxyproline fractions) with activation of hyaluronidases, matrix metalloproteinases (MMP), α2-macroglobulin and an increased content of tissue inhibitors of MMP (TIMP-1 and TIMP-2) with respect to group 1 data. In group 3, changesin the structure of proteoglycans were noted (an increase in the content of uronic acids and galactose), a decrease in the content of hyaluronan and free hydroxyproline, an increase in the activity of hyaluronidases. The MMP activity and the TIMP content corresponded to the data of group 2. In group 4, the content of uronic acids and galactose in proteoglycans also increased, but peptide-bound hydroxyproline decreased and the hyaluronan content more noticeably decreased. The activity of all enzymes regulating the ECM metabolism reduced with respect to the data of group 2.Thus, intraperitoneal administration of LEDZ to infected mice led to activating hyaluronidases, changing the structure of proteoglycans, and decreasing the free hydroxyproline content. Inhalation administration of LEDZ, along with changes in the structure of proteoglycans, reduced the activity of MMP, hyaluronidases, α2-macroglobulin, the content of TIMP-1 and TIMP-2, peptide-bound hydroxyproline. The antifibrotic effect of LEDZ with inhalation administration was manifested in a decrease in peptide-bound hydroxyproline and in a more significant decrease in hyaluronan compared with intraperitoneal administration.Thus, intraperitoneal administration of LEDZ to infected mice led to activating hyaluronidases, changing the structure of proteoglycans, and decreasing the free hydroxyproline content. Inhalation administration of LEDZ, along with changes in the structure of proteoglycans, reduced the activity of MMP, hyaluronidases, α2-macroglobulin, the content of TIMP-1 and TIMP-2, peptide-bound hydroxyproline. The antifibrotic effect of LEDZ with inhalation administration was manifested in a decrease in peptide-bound hydroxyproline and in a more significant decrease in hyaluronan compared with intraperitoneal administration.

The genetic resistance of sows to Escherichia coli F4 adhesion reduces their response to a vaccine containing F4 fimbriae but does not affect the preweaning performance of their susceptible piglets.

Pigs without intestinal receptors for F4 fimbriae are congenitally resistant to F4 fimbriae-bearing enterotoxigenic Escherichia coli (ETEC F4). In general, 50 % and 100 % of piglets born to resistant (RR) sows crossed with hetero- or homozygous susceptible (SR, SS) boars, respectively, are susceptible but do not receive colostral antibodies against F4 fimbriae unless the sows have been vaccinated. The question arises as to whether resistant sows produce protective amounts of F4 antifimbrial antibodies after vaccination. The serum and colostrum antibody titres of 12 resistant and 12 susceptible vaccinated gilts were compared. The effect of the receptor status of the dam and sire on the preweaning performance of 5027 piglets was evaluated using Agroscope's recordings. The sows of the experimental herd, where ETEC F4 was circulating, were vaccinated against ETEC twice during the first pregnancy and once during each following pregnancy. The log2 transformed F4 antibody titres in the serum obtained after the second vaccine injection as well as in the colostrum of the 12 resistant animals were lower than the titres of the susceptible animals (serum: F4ab 11,19 ± 1,44 vs. 12,18 ± 1,33, P = 0,096; F4ac 10,03 ± 1,58 vs. 11,59 ± 1,43, P = 0,019; colostrum: F4ab 12,20 ± 2,41 vs. 14,02 ± 1,31, P = 0,033; F4ac 10,93 ± 2,46 vs. 13,03 ± 5,21, P = 0,006). The heat labile enterotoxin (LT) antibody titres after vaccination did not differ between susceptible and resistant animals (p > 0,10). Preweaning mortality in the offspring of RR sows × SS boars was slightly lower than in the offspring of SS sows × RR boars (P = 0,04), suggesting that the disease risk of susceptible piglets born to vaccinated resistant sows was not increased, even though they received colostrum with a slightly reduced content of antibody against F4 fimbriae.

Dendritic Cell-Hitchhiking In Vivo for Vaccine Delivery to Lymph Nodes.

Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the "One-to-Many" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation.

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

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. 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. 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. 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.

A dendritic cell-recruiting, antimicrobial blood clot hydrogel for melanoma recurrence prevention and infected wound management

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management.

Innate immune responses against mRNA vaccine promote cellular immunity through IFN-β at the injection site

mRNA vaccines against SARS-CoV-2 have revolutionized vaccine development, but their immunological mechanisms are not fully understood. Here, we investigate injection site responses of mRNA vaccines by generating a comprehensive single-cell transcriptome profile upon lipid nanoparticle (LNP) or LNP-mRNA challenge in female BALB/c mice. We show that LNP-induced stromal pro-inflammatory responses and mRNA-elicited type I interferon responses dominate the initial injection site responses. By tracking the fate of delivered mRNA, we discover that injection site fibroblasts are highly enriched with the delivered mRNA and that they express IFN-β specifically in response to the mRNA component, not to the LNP component of mRNA vaccines. Moreover, the mRNA-LNP, but not LNP alone, induces migratory dendritic cells highly expressing IFN-stimulated genes (mDC_ISGs) at the injection site and draining lymph nodes. When co-injected with LNP-subunit vaccine, IFN-β induces mDC_ISGs at the injection site, and importantly, it substantially enhances antigen-specific cellular immune responses. Furthermore, blocking IFN-β signaling at the injection site significantly decreases mRNA vaccine-induced cellular immune responses. Collectively, these data highlight the importance of injection site fibroblasts and IFN-β signaling during early immune responses against the mRNA vaccine and provide detailed information on the initial chain of immune reactions elicited by mRNA vaccine injection.

Multimodal profiling of biostabilized human skin modules reveals a coordinated ecosystem response to injected mRNA-1273 COVID-19 vaccine.

The field of drug development is witnessing a remarkable surge in the development of innovative strategies. There is a need to develop technological platforms capable of generating human data prior to progressing to clinical trials. Here we introduce a new flexible solution designed for the comprehensive monitoring of the natural human skin ecosystem's response to immunogenic drugs over time. Based on unique bioengineering to preserve surgical resections in a long survival state, it allows for the first time a comprehensive analysis of resident immune cells response at both organ and single-cell levels. Upon injection of the mRNA-1273 COVID-19 vaccine, we characterized precise sequential molecular events triggered upon detection of the exogenous substance. The vaccine consistently targets DC/macrophages and mast cells, regardless of the administration route, while promoting specific cell-cell communications in surrounding immune cell subsets. Given its direct translational relevance, this approach provides a multiscale vision of genuine human tissue immunity that could pave the way toward the development of new vaccination and drug development strategies.

Intranasal Delivery of Quillaja brasiliensis Saponin-Based Nanoadjuvants Improve Humoral Immune Response of Influenza Vaccine in Aged Mice.

Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines.