Differential polyvalent passive immune protection of egg yolk antibodies (IgY) against live and inactivated Vibrio fluvialis in fish.

Egg yolk antibodies (IgY) can be prepared in large quantities and economically, and have potential value as polyvalent passive vaccines (against multiple bacteria) in aquaculture. This study prepared live and inactivated Vibrio fluvialis IgY and immunized Carassius auratus prior to infection with V. fluvialis and Aeromonas hydrophila. The results showed that the two IgY antibodies hold effective passive protective rates against V. fluvialis and A. hydrophila in C. auratus. Further, the serum of C. auratus recognized the two bacteria in vitro, with a decrease in the bacteria content of the kidney. The phagocytic activity of C. auratus plasma was enhanced, with a decrease in the expression of inflammatory and antioxidant factors. Pathological sections showed that the kidney, spleen, and intestinal tissue structures were intact, and apoptosis and DNA damage decreased in kidney cells. Moreover, the immunoprotection conferred by the live V. fluvialis IgY was higher than that of the inactivated IgY. Addition, live V. fluvialis immunity induced IgY antibodies against outer membrane proteins of V. fluvialis were more than inactivated V. fluvialis immunity. Furthermore, heterologous immune bacteria will not cause infection, so V. fluvialis can be used to immunize chickens to obtain a large amount of IgY antibody. These findings suggest that the passive immunization effect of live bacterial IgY antibody on fish is significantly better than that of inactivated bacterial antibody, and the live V. fluvialis IgY hold potential value as polyvalent passive vaccines in aquaculture.

Does Phage Therapy Need a Pan-Phage?

The emergence of multidrug-resistant bacteria is undoubtedly one of the most serious global health threats. One response to this threat that has been gaining momentum over the past decade is 'phage therapy'. According to this, lytic bacteriophages are used for the treatment of bacterial infections, either alone or in combination with antimicrobial agents. However, to ensure the efficacy and broad applicability of phage therapy, several challenges must be overcome. These challenges encompass the development of methods and strategies for the host range manipulation and bypass of the resistance mechanisms developed by pathogenic bacteria, as has been the case since the advent of antibiotics. As our knowledge and understanding of the interactions between phages and their hosts evolves, the key issue is to define the host range for each application. In this article, we discuss the factors that affect host range and how this determines the classification of phages into different categories of action. For each host range group, recent representative examples are provided, together with suggestions on how the different groups can be used to combat certain types of bacterial infections. The available methodologies for host range expansion, either through sequential adaptation to a new pathogen or through genetic engineering techniques, are also reviewed.

Polyvalent mpox mRNA vaccines elicit robust immune responses and confer potent protection against vaccinia virus.

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

Polyvalent Aptamer-Functionalized NIR-II Quantum Dots for Targeted Theranostics in High PD-L1-Expressing Tumors.

Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.

Naja nigricincta nigricincta venom, a murine model. Evaluation of skeletal and cardio-myonecrosis, kidney injury and inflammatory response along with neutralisation efficacy by the SAIMR/SAVP - And EchiTAb-Plus-ICP polyvalent antivenoms.

African spitting cobra, Naja nigricincta nigricincta (Zebra snake), envenomation is an important cause of snakebite morbidity and mortality in Namibia. The snake is endemic to central and northern Namibia as well as southern Angola. The venom is mainly cytotoxic, resulting in aggressive dermo-necrosis and often accompanied by severe systemic complications. No specific antivenom exists. Rhabdomyolysis, systemic inflammatory response, haemostatic abnormalities, infective necrotising fasciitis as well as acute kidney failure have been documented. Based on murine models, this study assessed SAVP/SAIMR - and EchiTAb-Plus-ICP polyvalent antivenom neutralisation as well as subdermal necrosis. Additional muscle, cardiac, kidney and lung histology, creatine kinase measurements and post-mortems were performed. An intravenous median lethal dose (LD50) of Naja nigricincta nigricincta venom was determined at 18.4 (CI: 16.3; 20.52) µg and a subdermal lethal dose at 15.3(CI: 12.96; 17.74)µg. The SAIMR/SAVP polyvalent antivenom median effective dose (ED50) was 1.2 ml antivenom/1 mg venom equating to a potency (WHO) of 1 ml antivenom neutralising 0.63 mg venom and approximately 240 ml (24 vials) needed for initial treatment. The ED50 of the EchiTAb-Plus-ICP was 1 ml antivenom/1 mg venom and a potency of 65 mg venom/ml antivenom (3.3 x LD50), estimating 230 ml (23 vials) for treatment. Histology and serology (creatine kinase) evidenced venom induced skeletal myotoxicity, which was not prevented by the antivenoms tested. Cardiac myonecrosis, an inflammatory response, direct venom kidney tubular necrosis and cardio-pulmonary failure were documented.

Viperidae snake envenomation from a highly complex hospital in southwestern Colombia.

Background: Snake envenomation is a medical condition with high morbidity and mortality in southwestern Colombia. Objectives: To describe the characteristics of the envenomation caused by Viperidae snakes view in a highly complex hospital in Southwestern Colombia. Methods: A cross-sectional study was carried out. Patients treated for Viperidae snake envenomation from 2001 to 2020 in a Hospital Fundación Valle del Lili, Cali, Colombia, were studied. Results: Twenty-eight patients were included. Envenomation was caused by the genera Bothrops, Bothriechis, Porthidium, and Bothrocophias. The median age was 37.7 (±20.6), and they were predominantly male (19, 68%). Bites occurred on the upper extremities in 16 (57%) patients. Pain (23, 81%) and edema (22, 78%) were the most common clinical symptoms. Thirteen (46%) patients presented coagulopathy. Prolonged prothrombin and activated partial thromboplastin times were common: (22, 78% and 15, 53%, respectively). Twenty (71%) patients were treated with polyvalent antivenom (median dose of 6 (2-15) vials). The median time between the accident and antivenom administration was 9 h (5.5-17). Door-to-needle time was 37.5 (0-62) min. Eighteen (64%) patients were admitted to the intensive care unit. Three (11%) patients had serum sickness. Seven (25%) developed infectious complications, four (14%) had surgery, one (3%) had compartment syndrome, one (3%) underwent amputation of the affected limb, and one (3%) patient died. Conclusions: Local manifestations and coagulopathy were common clinical features. Polyvalent antivenom was an effective treatment for disease control. Significant complications were associated with delays in seeking medical care.

Mg2+-promoted high-efficiency DNA conjugation on polydopamine surfaces for aptamer-based ochratoxin A detection.

BACKGROUND: Surface immobilization of DNA is the foundation of a broad range of applications in biosensing and specific DNA extraction. Polydopamine (PDA) coatings can serve as intermediate layers to immobilize amino- or thiol-labelled molecules, including DNA, onto various materials through Michael addition and/or Schiff base reactions. However, the conjugation efficiency is limited by electrostatic repulsion between negatively charged DNA and PDA. Recently, it has been reported that polyvalent metal ions (such as Mg2+ and Ca2+) can mediate the adsorption of DNA on PDA surfaces. Inspired by this, in this work we aimed to exploit polyvalent metal ions to facilitate the conjugation of DNA on PDA. RESULTS: Mg2+ was used to promote the conjugation of amino-terminated DNA complementary to ochratoxin A (OTA) aptamer (cDNA-NH2) on PDA-coated magnetic nanoparticles (Fe3O4@PDA). After the reaction, the unlinked cDNA-NH2 adsorbed on Fe3O4@PDA mediated by Mg2+ was removed with EDTA. In the presence of 20 mM Mg2+, the amount of covalently linked cDNA-NH2 increased approximately 11-fold compared to that in the absence of Mg2+. The resulting Fe3O4@PDA@cDNA conjugates exhibited superior hybridization capacity towards OTA aptamers, minimal nonspecific adsorption, and excellent chemical stability. The conjugates combined with fluorophore-labelled aptamers were employed for OTA detection, achieving a limit of detection (LOD) of 2.77 ng mL-1. To demonstrate versatility, this conjugation method was extended to Ca2+-promoted conjugation of cDNA-NH2 on Fe3O4@PDA nanoparticles and Mg2+-promoted conjugation of cDNA-NH2 on PDA-coated 96-well plates. SIGNIFICANCE: The conjugation efficiency of DNA on PDA was significantly improved with the assistance of polyvalent metal ions (Mg2+ and Ca2+), providing a facile and efficient method for DNA immobilization. Due to the substrate-independent adhesion property of PDA, this method demonstrates versatility in DNA surface modification and holds great potential for applications in target extraction, biosensing, and other fields.

Comparison of the safety and efficacy of the wild-type and lpxL/lpxM mutant inactivated vaccine against the avian pathogenic Escherichia coli O1, O2, and O78 challenge.

Avian pathogenic Escherichia coli (APEC) is primarily responsible for causing septicemia, pneumonitis, peritonitis, swollen head syndrome, and salpingitis in poultry, leading to significant losses in the poultry sector, particularly within the broiler industry. The removal of the lpxL and lpxM genes led to an eightfold decrease in the endotoxin levels of wild APEC strains. In this study, mutant strains of lpxL/lpxM and their O1, O2, and O78 wild-type strains were developed for an inactivated vaccine (referred to as the mutant vaccine and the wild-type vaccine, respectively), and the safety and effectiveness of these two prototype vaccines were assessed in white Leghorn chickens. Findings indicated that chickens immunized with the mutant vaccine showed a return of appetite sooner post-immunization and experienced earlier disappearance of nodules at the injection site compared to those immunized with the wild-type vaccine. Pathological examinations revealed that lesions were still present in the liver, lung, and injection site in chickens vaccinated with the wild-type vaccine 14 days post-vaccination (dpv), whereas no lesions were found in chickens vaccinated with the mutant vaccine at 14 dpv. There were no significant differences in antibody levels on the challenge day or in mortality or lesion scores between challenged birds immunized with either the mutant vaccine or the wild-type vaccine at the same dose. In this study, the safety of a single dose or overdose of the mutant vaccine and its efficacy at one dose were evaluated in broilers, and the results showed that the mutant vaccine had no adverse effects on or protected vaccinated broilers from challenge with the APEC O1, O2, or O78 strains. These results demonstrated that the mutant polyvalent inactivated vaccine is a competitive candidate against APEC O1, O2, and O78 infection compared to the wild-type vaccine.

Evaluation of protective efficacy, serological responses, and cytokine modulation induced by polyvalent Leptospira vaccines in hamsters.

Whole-cell inactivated vaccines (bacterins) are the only licensed vaccines available for leptospirosis prevention and control, especially in domestic and farm animals. However, despite their widespread use, inconsistencies in their efficacy have been reported. Because immunity induced by bacterins is mainly mediated by antibodies against leptospiral lipopolysaccharides, the involvement of cellular responses is not well-known. The aim of this study was to investigate the efficacy and characterize the humoral and cellular immune responses induced by whole-cell inactivated leptospirosis bacterin formulations containing serovars Bratislava, Canicola, Copenhageni, Grippotyphosa, Hardjoprajitno, and Pomona. For the potency test, hamsters were immunized with one dose of polyvalent bacterins (either commercial or experimental) and then challenged with a virulent Pomona strain. Serological (MAT and IgM and IgG-ELISA) and cellular (cytokine transcription in blood evaluated by RT-qPCR) analyses were performed. The results revealed that vaccination with either bacterin formulation was able to protect 90-100% of the hamsters infected with the Pomona serovar, although most of the surviving animals remained as renal carriers. Specific agglutinating antibodies and significant levels of IgM, IgG, and IgG2 (P < 0.05) that were able to react with the six serovars present in the vaccine formulations were produced, indicating that the vaccines can potentially provide immunity against all strains. The protective immunity of these vaccines was mainly mediated by balanced a Th1/Th2 response, characterized by increased IFN-γ, IL-10 and IL-α transcription. These data support the importance of characterizing immunological responses involved in bacterin efficacy and investing in the improvement of these vaccine formulations.

Ternary Nanostructure Coupling Flip-Flap Origami-Based Aptasensor for the Detection of Dengue Virus Antigens.

There is currently a lot of interest in the construction of point-of-care devices stemming from paper-based origami biosensors. These devices demonstrate how paper's foldability permits the construction of sensitive, selective, user-friendly, intelligent, and maintainable analytical devices for the detection of several ailments. Herein, the first example of the electrochemical aptasensor-based polyvalent dengue viral antigen detection using the origami paper-folding method is presented. Coupling it with an aptamer leads to the development of a new notation known as OBAs, or origami-based aptasensor, that presents a multitude of advantages to the developed platform, such as assisting in safeguarding the sample from air-dust particles, providing confidentiality, and providing a closed chamber to the electrodes. In this paper, gold-decorated nanocomposites of zinc and graphene oxide (Au/ZnO/GO) were synthesized via the chemical method, and characterization was conducted by Scanning Electron Microscope, Transmission Electron Microscope, UV-Vis, and XRD which reveals the successful formation of nanocomposites, mainly helping to enhance the signal and specificity of the sensor by employing aptamers, since isolation and purification procedures are not required. The biosensor that is being demonstrated here is affordable, simple, and efficient. The reported biosensor is an OBA detection of polyvalent antigens of the dengue virus in human serum, presenting a good range from 0.0001 to 0.1 mg/mL with a limit of detection of 0.0001 mg/mL. The reported single-folding ori-aptasensor demonstrates exceptional sensitivity, specificity, and performance in human serum assays, and can also be used for the POC testing of various viral infections in remote areas and underdeveloped countries, as well as being potentially effective during outbreaks. Highlights: (1) First report on origami-based aptasensors for the detection of polyvalent antigens of DENV; (2) In-house construction of low-cost origami-based setup; (3) Gold-decorated zinc/graphene nanocomposite characterization was confirmed via FESEM/UV-Vis/FTIR; (4) Cross-reactivity of dengue-aptamer has been deduced; (5) Electrochemical validation was conducted through CV.

A polyvalent RNA vaccine reduces the immune imprinting phenotype in mice and induces neutralizing antibodies against omicron SARS-CoV-2.

Immune imprinting is now evident in COVID-19 vaccinated people. This phenomenon may impair the development of effective neutralizing antibodies against variants of concern (VoCs), mainly Omicron and its subvariants. Consequently, the boost doses with bivalent vaccines have not shown a significant gain of function regarding the neutralization of Omicron. The approach to design COVID-19 vaccines must be revised to improve the effectiveness against VoCs. Here, we took advantage of the self-amplifying characteristic of RepRNA and developed a polyvalent formulation composed of mRNA from five VoCs. LION/RepRNA Polyvalent induced neutralizing antibodies in mice previously immunized with LION/RepRNA D614G and reduced the imprinted phenotype associated with low neutralization capacity of Omicron B.1.1.529 pseudoviruses. The polyvalent vaccine can be a strategy to handle the low neutralization of Omicron VoC, despite booster doses with either monovalent or bivalent vaccines.

Multivalence-State Tungsten Species Facilitated Iridium Loading for Robust Acidic Water Oxidation.

The development of the proton exchange membrane water electrolyzer (PEMWE) is still limited by the prohibitive cost and scarcity of iridium (Ir)-based oxygen evolution reaction (OER) catalyst. This work presents a novel catalyst synthesized by precursor-atomization and rapid joule-heating method, successfully doping iridium atoms into polyvalent tungsten blends (W0 , W5+ , W6+ ) based on titanium substrate. The vacancy engineering of unsaturated tungsten oxide (W5+ , W6+ ) reconstructs the electronic structure of the catalyst surface, which resulting in the low-valence state iridium species, avoiding excessive oxidation of iridium and accelerating the catalytic kinetics. Meanwhile, metallic tungsten (W0 ) improves the conductivity of catalyst and guarantees the stable existence of oxygen vacancy. The TiIrWOx possesses excellent performance in acidic OER catalysis, requiring overpotential of only 181 mV to drive 10.0 mA cm-2 , and exhibiting a high mass activity of 753 A gIr -1 at an overpotential of 300 mV. The membrane electrode assembly (MEA) with TiIrWOx as anode electrocatalyst can reduce the Ir consumption amount by >60% compared to commercial IrO2 , and it can operated over 120 h at a current density of 1.0 A cm-2 .

Identification of poorly immunodepleted phospholipase A2 (PLA2) proteins of Bungarus fasciatus venom from Assam, India and evaluation of Indian polyvalent antivenom using third-generation antivenomics.

Bungarus fasciatus also referred to as the Banded krait is a snake which possesses venom and belongs to the Elapidae family. It is widely distributed across the Indian subcontinent and South East Asian countries and is responsible for numerous snakebites in the population. B. fasciatus possesses a neurotoxic venom and envenomation by the snake results in significant morbidity and occasional morbidity in the victim if not treated appropriately. In this study, the efficacy of Indian polyvalent antivenom (Premium Serums polyvalent antivenom) was evaluated against the venom of B. fasciatus from Guwahati, Assam (India) employing the Third-generation antivenomics technique followed by identification of venom proteins from three poorly immunodepleted peaks (P5, P6 and P7) using LC-MS/MS analysis. Seven proteins were identified from the three peaks and all these venom proteins belonged to the phospholipase A2 (PLA2) superfamily. The identified PLA2 proteins were corroborated by the in vitro enzymatic activities (PLA2 and Anticoagulant activity) exhibited by the three peaks and previous reports of pathological manifestation in the envenomated victims. Neutralization of enzymatic activities by Premium Serums polyvalent antivenom was also assessed in vitro for crude venom, P5, P6 and P7 which revealed moderate to poor inhibition. Inclusion of venom proteins/peptides, which are non-immunodepleted or poorly immunodepleted, into the immunization mixture of venom used for antivenom production may help in enhancing the efficacy of the polyvalent antivenom.

Polyvalency: an emerging trend in the development of clinical antibodies.

Medicine has benefited greatly from the development of monoclonal antibody (mAb) technology. First-generation mAbs have seen significant success in the treatment of major diseases, such as autoimmune, inflammation, cancer, infectious, and cardiovascular diseases. Developing next-generation antibodies with improved potency, safety, and non-natural characteristics is a booming field of mAb research. In this review, we discuss the significance of polyvalency and polyvalent antibodies, as well as important findings from preclinical studies and clinical trials involving polyvalent antibodies. We then review the role of tumor necrosis factor-alpha (TNF-α) in inflammatory diseases and the need for polyvalent anti-TNF-α antibodies.

In-depth immunorecognition and neutralization analyses of Micrurus mipartitus and M. dumerilii venoms and toxins by a commercial antivenom.

In Colombia, the Micrurus genus comprises 30 species, including M. mipartitus and M. dumerilii, which are of major clinical relevance due to their wide geographical distribution and the number of snakebites inflicted by them. These neurotoxic envenomations are characterized by neuromuscular paralysis attributed to venom components such as three-finger toxins (3FTx) and phospholipases (PLA2). Additionally, there is limited information available on the neutralizing coverage of commercially available antivenoms, underscoring the need to perform studies to assess the cross-neutralizing ability of these life-saving products. Therefore, we present an in-depth immunorecognition analysis by the anticoral-INS antivenom from Colombia on the M. mipartitus and M. dumerilii venoms. The antivenom cross-recognized the whole venoms and their components with different intensities. For instance, the antivenom showed better recognition on PLA2s than on 3FTxs in both venoms. Moreover, at doses tested, the antivenom totally neutralized the lethal effect of M. dumerilii venom; however, it did not neutralize this effect induced by M. mipartitus venom and its main toxic components from the southwestern region of the department of Antioquia. Furthermore, the anticoral-INS antivenom displayed better cross-immunorecognition of PLA2-predominant Micrurus venoms than of 3FTx-predominant Micrurus venoms. This highlights the need to include venoms from both types of venom patterns in the immunization mixture to produce antivenoms against coral snakes. Finally, our results suggest the need for further research to optimize the composition of immunizing mixtures for antivenom production and improve their efficacy against coral snake envenomation in Colombia and the Americas.

Prolonged venom-induced consumptive coagulopathy following Mangshan pit viper (Protobothrops mangshanensis) envenomation despite Hemato Polyvalent antivenom administration.

This case report summarizes an envenomation by the Mangshan pit viper (Protobothrops mangshanensis), a rare, endangered, venomous snake endemic to Mount Mang of China, and the first reported use of Hemato Polyvalent antivenom (HPAV) for this species. The snakebite occurred in a United States zoo to a 46-year-old male zookeeper. He presented via emergency medical services to a tertiary center after sustaining a single P. mangshanensis bite to the abdomen and was transported with antivenom from the zoo. Within 2 hours of envenomation, he developed oozing of sanguineous fluid and ecchymosis at the puncture site, and about 4 hours post-bite, was treated with HPAV. His coagulation profile fluctuated with the following pertinent peak/nadir laboratory values and corresponding hospital day (HD): undetectable fibrinogen levels, d-dimer 8.89 mg/L and 7.43 mg/L, and INR 2.97 and 1.46 on HD zero and three, respectively. Other peak/nadir values included hemoglobin 9.7 g/dL and creatinine phosphokinase 2410 U/L on HD four and platelets 81 × 109/L on HD seven. The patient received a total of 30 vials of HPAV over 5 days and 1 unit of cryoprecipitate on HD six. Upon discharge on HD eight, laboratory studies were normalizing, except for platelets, and edema stabilized. This case describes an acute, recurrent, and prolonged venom-induced consumptive coagulopathy despite prompt administration and repeated doses of HPAV.

Systematic review and meta-analysis on the efficacy of Indian polyvalent antivenom against the Indian snakes of clinical significance.

Snakebite in India is a severe problem as it causes a mortality rate of 58,000 and a disability rate of 140,000 every year which is the highest among any other country. Antivenom is the primary therapy for snakebite, and its manufacturing techniques have essentially stayed unaltered for over a century. Indian polyvalent antivenom, a scientifically validated medicine for treating the toxic effects of snakebites, is available against the venom of the so-called Big Four snakes namely Spectacled cobra (Naja naja), Saw-scaled viper (Echis carinatus), Russell's viper (Daboia russelli) and the Common krait (Bungarus caeruleus), responsible for majority of the deaths in India. India hosts many other species of snakes, including cobras, kraits, saw-scaled vipers, sea snakes, and pit vipers, responsible for clinically severe envenomation. Neutralization strategy has been applied to access the efficacy of antivenoms, crucial for reducing snake bite deaths and disabilities. This review aims to conduct a systematic review and meta-analysis on the neutralization efficiency of the Polyvalent Antivenom (PAV) and focus on the factors that may contribute to the poor recognition of the antivenom towards the venom toxins. Reports focusing on the investigation of antivenom efficacy were searched and collected from several databases. Preclinical studies that reported the neutralization efficacy of the commercial antivenom against the medically important snakes of India were included. The articles were screened based on the inclusion criteria and 8 studies were shortlisted for meta-analysis. Pooled proportion was calculated for the antivenom efficacy reported by the studies and was found to be statistically significant with a 95% confidence interval. The heterogenicity in the venom toxicity and neutralization potency of the antivenom was evident in the overall estimate (proportion) and individual data. We provide comprehensive evidence on antivenom efficacy against medically important snakes from various parts of India which may aid in identifying the gaps in snake envenomation therapy and the need for novel potentially improved treatment of snakebites.

Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches.

The Varicella Zoster Virus (VZV) presents a global health challenge due to its dual manifestations of chickenpox and shingles. Despite vaccination efforts, incomplete coverage, and waning immunity lead to recurrent infections, especially in aging and immunocompromised individuals. Existing vaccines prevent chickenpox but can trigger the reactivation of shingles. To address these limitations, we propose a polyvalent multiepitope subunit vaccine targeting key envelope glycoproteins of VZV. Through bioinformatics approaches, we selected six glycoproteins that are crucial for viral infection. Epitope mapping led to the identification of cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell linear (LBL) epitopes. Incorporating strong immunostimulants, we designed two vaccine constructs, demonstrating high antigenicity, solubility, stability, and compatibility with Toll-like receptors (TLRs). Molecular docking and dynamics simulations underscored the stability and affinity of the vaccine constructs with TLRs. These findings lay the foundation for a comprehensive solution to VZV infections, addressing the challenges of incomplete immunity and shingles reactivation. By employing advanced immunoinformatics and dynamics strategies, we have developed a promising polyvalent multiepitope subunit vaccine candidate, poised to enhance protection against VZV and its associated diseases. Further validation through in vivo studies is crucial to confirm the effectiveness and potential of the vaccine to curb the spread of VZV. This innovative approach not only contributes to VZV control but also offers insights into tailored vaccine design strategies against complex viral pathogens.

Effect of killed autogenous polyvalent vaccines against Vibrio harveyi, V. alginolyticus and Streptococcus iniae on survival and immunogenicity of Asian seabass (Latescalcarifer).

Vibriosis and Streptococcosis are the most important bacterial diseases that infect Asian seabass (Lates calcarifer) in various stages of its life cycle. Vaccination is a cost-effective strategy to prevent the occurrence of infectious diseases and increase sustainability in the aquaculture industry. This study was aimed to develop and evaluate a killed polyvalent vaccine against Vibrio harveyi, V. alginolyticus and Streptococcus iniae, delivered by intraperitoneal injection in Asian seabass. The fish were divided into three groups with 60 fish in triplicate: I) a control group injected with phosphate-buffered saline (PBS), II) a group vaccinated by polyvalent vaccine (V. alginolyticus + V. harveyi + S. iniae) and III) a group vaccinated with the same polyvalent vaccine plus an oral booster. Immunological parameters and antibody titer were measured before and at three, five-, and eight-weeks post-vaccination. The efficacy of the killed vaccine was assessed five weeks post-vaccination by challenging with each isolate separately. The vaccinated groups had higher survival rate than control group. The highest relative percentage survival rate, 85.71 ± 3.57 % was observed in group III when challenged with V. harveyi. The vaccinated fish produced significantly higher antibody titers against V. alginolyticus, V. harveyi and S. iniae than the control group (P < 0.05). Non-specific immune parameters were significantly enhanced in the vaccinated groups, especially group III, compared to the control. The results demonstrated that the administration of a killed polyvalent vaccine can effectively protect Asian seabass against V. alginolyticus, V. harveyi and S. iniae.

Polyvalent passive vaccine candidates from egg yolk antibodies (IgY) of important outer membrane proteins (PF1380 and ExbB) of Pseudomonas fluorescens in fish.

Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1ß) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.