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Polyvalent passive vaccines can act fast in resisting various bacteria with good efficacy, and they have application value in aquaculture. This study prepared live and inactivated Vibrio fluvialis mouse antisera (L-VF-antiserum and I-VF-antiserum), and administered them to goldfish (Carassius auratus) infected with V. fluvialis and Aeromonas hydrophila. The passive protective rates of live and inactivated mouse antisera against V. fluvialis were 60% (p < 0.05) and 40% (p < 0.05), and their passive cross-protective rates against A. hydrophila were 42.86% (p < 0.05) and 35.71% (p < 0.05), respectively. Furthermore, the two mouse antisera could recognize the bacteria in vitro; the content of bacteria in the C. auratus kidney decreased (p < 0.05), the phagocytic activity of C. auratus leukocytes was enhanced (p < 0.05), and the expression of inflammatory genes and activity of antioxidant factors decreased (p < 0.05). Moreover, the kidney, spleen, and intestinal tissue structures were intact, and the apoptosis and DNA damage were decreased (p < 0.05) among the kidney cells. The live V. fluvialis antiserum contained more antibodies against the outer membrane proteins of V. fluvialis than the inactivated mouse antiserum. The immunoprotective abilities of the live V. fluvialis antiserum were higher than those of the inactivated antiserum, and the antiserum of live V. fluvialis immunity demonstrated potential application value as a polyvalent passive immune vaccine in fish. [ABSTRACT FROM AUTHOR]

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 Tolllike 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. [ABSTRACT FROM AUTHOR]

Polyvalent passive vaccines can act fast in resisting various bacteria with good efficacy, and they have application value in aquaculture. This study prepared live and inactivated Vibrio fluvialis mouse antisera (L-VF-antiserum and I-VF-antiserum), and administered them to goldfish (Carassius auratus) infected with V. fluvialis and Aeromonas hydrophila. The passive protective rates of live and inactivated mouse antisera against V. fluvialis were 60% (p < 0.05) and 40% (p < 0.05), and their passive cross-protective rates against A. hydrophila were 42.86% (p < 0.05) and 35.71% (p < 0.05), respectively. Furthermore, the two mouse antisera could recognize the bacteria in vitro; the content of bacteria in the C. auratus kidney decreased (p < 0.05), the phagocytic activity of C. auratus leukocytes was enhanced (p < 0.05), and the expression of inflammatory genes and activity of antioxidant factors decreased (p < 0.05). Moreover, the kidney, spleen, and intestinal tissue structures were intact, and the apoptosis and DNA damage were decreased (p < 0.05) among the kidney cells. The live V. fluvialis antiserum contained more antibodies against the outer membrane proteins of V. fluvialis than the inactivated mouse antiserum. The immunoprotective abilities of the live V. fluvialis antiserum were higher than those of the inactivated antiserum, and the antiserum of live V. fluvialis immunity demonstrated potential application value as a polyvalent passive immune vaccine in fish.

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.

The article "Corrigendum: Designing a polyvalent vaccine targeting multiple strains of varicella zoster virus using integrated bioinformatics approaches" was published in Frontiers in Microbiology in 2024. The study was conducted by a team of researchers from various institutions in Bangladesh, India, China, and Canada. The corrigendum addresses an error in the Acknowledgments section, clarifying that the study did not receive any funding from internal or external sources. The original article has been updated to reflect this correction. [Extracted from the article]

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.

Among aquaculture vaccines, polyvalent vaccines (for immunoprotection against multiple bacterial species) are more efficient and can better avoid bacterial resistance and antibiotic residues in fish. Here, 15 outer membrane proteins (OMPs) of Aeromonas hydrophila were cloned and purified, and mouse antisera were prepared. Passive immunization to Carassius auratus showed that four OMPs sera (OmpW, OmpAII, P5, and AHA2685) and the entire OMPs serum held effective immunoprotection against A. hydrophila infection. Furthermore, the active immunization of four OMPs to C. auratus showed that OmpW, OmpAII, P5, and AHA2685 held effective immunoprotection against A. hydrophila , and OmpW held active cross-protection against Vibrio alginolyticus. The mechanisms of these four candidate vaccines in triggering immune responses were subsequently explored. They all could activate innate immune responses in active immunization, down-regulate (p < 0.05) the inflammation-related genes expression to reduce the inflammatory reaction induced by A. hydrophila , and down-regulate (p < 0.05) antioxidant-related factors to reduce the antioxidant reaction for bacterial infection. Noteablely, the four OMPs had protective abilities on kidney and spleen tissues of C. auratus after challenged with A. hydrophila and V. alginolyticus by histopathological observation. Collectively, our results identify OmpW as a polyvalent vaccine candidate, and OmpAII, P5, and AHA2685 as vaccine candidates against A. hydrophila infection in fish. • 15 outer membrane proteins of Aeromonas hydrophila were cloned and purified, and antisera were prepared. • OmpW, OmpAII, P5, and AHA2685 have the passive protective ability to Carassius auratus. • OmpW, OmpAII, P5, and AHA2685 have active protective ability while OmpW has active cross-protective ability in C. auratus. • OmpW is a polyvalent vaccine candidate, and OmpAII, P5, and AHA2685 are vaccines against A. hydrophila in aquaculture. [ABSTRACT FROM AUTHOR]

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. • The IgY antibodies against live and inactivated Vibrio fluvialis were prepared. • The two IgY antibodies can activate the innate immune responses in Carassius auratus. • The two IgY antibodies have the passive and passive cross-protective abilities to C. auratus. • The IgY antibody against live V. fluvialis can be considered polyvalent passive vaccine candidates in aquaculture. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Multiple MPXV antigens are expressed in one mRNA molecule by a 2A peptide • All polyvalent MPXV mRNA vaccines induce robust immune responses to EEV and IMV antigens • The tetravalent MPXV mRNA vaccines encoding MPXV A35, B6, A29, M1 provide potent protection Ye et al. demonstrate that both the bivalent and tetravalent MPXV mRNA vaccines encoding at least one of EEV and IMV antigens induce robust antigen-specific humoral and cellular immune responses in mice. Furthermore, the two tetravalent vaccines LBAAM and LBA&LAM provide superior protective efficacy against VACV challenge. [ABSTRACT FROM AUTHOR]

The infectious bronchitis virus (IBV) is an acute and highly contagious disease, which affects chickens of all ages. Vaccination is the most important way to control this disease. Nevertheless, novel variant strains are constantly reported because of the lack of proofreading capabilities of RNA polymerase and high frequency of homologous RNA recombination. Cross-protection studies has demonstrated that the vaccines could provide great protective effects against viruses of same serotype or genotype. However, the protective effect of different commercial vaccines and vaccine combinations against the prevalent IBV strains in China has rarely been studied. Owing to the multiple genotype or serotype IBV strains prevalence in China, the polyvalent vaccines and their composition were used to expanding the protection spectrum of vaccine in practical application. To evaluate the protection of Chinese commercial IBV polyvalent vaccines against prevalent strains (QX-like and TW I-like), an immune challenge test was conducted. Four polyvalent vaccines, containing 4/91, H120, YX10p90, LDT3-A, and 28/86, were combined to form 8 vaccination strategies, almost all of which could provide more than 70% protection effects against challenge with QX-like strain. Particularly, the best protection rate (93%) was generated by administration the polyvalent vaccine C (H120 + 28/86 + 4/91) at 1 D of age and the polyvalent vaccine B (H120 + 4/91 + YX10p90) at 10 D of age. However, all the vaccination strategies in this study cannot provide great protective effects against TW-like strain, and more vaccines should be included in studies to expand the protection spectrum of vaccine. Therefore, for the newly emerging IBV strains, immunization with polyvalent vaccines via different vaccination strategies could be used to control the prevalence of IBV in a short time, whereas developing the homologous vaccines was not always necessary.

Meningococcal disease is the urgent problem of healthcare due to its widespread prevalence, high incidence, severe course and high risk of mortality. Vaccination of Russian Federation population with polyvalent meningococcal vaccine for serogroups A, C, W, Y has not been studied before within the framework of regional immunization programs. The article presents the results of epidemiological analysis of the situation on meningococcal disease in Tyumen region and Yamalo-Nenets autonomous district (YNAD) in 2014-2019. The obtained data were used to develop the immunization strategy against meningococcal disease within the framework of the regional immunization calendar in Tyumen region and regional immunization programs in YNAD. The clinical case of severe course of meningococcemia with complications is presented in the article. Clinical conditions and syndromes which are common for practice of therapists during the management of patients with generalized forms of meningococcal disease are described.

Bacterial infections cause huge losses in aquaculture and a wide range of health issues in humans. A vaccine is the most economical, efficient, and environment-friendly agent for protecting hosts against bacterial infections. This study aimed to identify broad, cross-protective antigens from the extracellular secretory proteome of the marine bacterium Vibrio alginolyticus. Of the 69 predicted extracellular secretory proteins in its genome, 16 were randomly selected for gene cloning to construct DNA vaccines, which were used to immunize zebrafish (Danio rerio). The innate immune response genes were also investigated. Among the 16 DNA vaccines, 3 (AT730_21605, AT730_22220, and AT730_22910) were protective against V. alginolyticus infection with 47–66.7% increased survival compared to the control, while other vaccines had lower or no protective effects. Furthermore, AT730_22220, AT730_22910, and AT730_21605 also exhibited cross-immune protective effects against Pseudomonas fluorescens and/or Aeromonas hydrophila infection. Mechanisms for cross-protective ability was explored based on conserved epitopes, innate immune responses, and antibody neutralizing ability. These results indicate that AT730_21605, AT730_22220, and AT730_22910 are potential polyvalent vaccine candidates against bacterial infections. Additionally, our results suggest that the extracellular secretory proteome is an antigen pool that can be used for the identification of cross-protective immunogens. [ABSTRACT FROM AUTHOR]

• History of combined and polyvalent vaccination is older than expected. • Italian expert of tropical medicine, Aldo Castellani, was probably the first to experiment both. • His typhoid-paratyphoid vaccine (TAB) was largely used during WWI with good results. Italian born and long term resident in England, Sir Aldo Castellani (1874–1971), is usually credited with "several discoveries of great importance in tropical medicine", most notably for his role in determining the aetiology of sleeping sickness and yaws. This contribution tries to highlight his role in the history of vaccinology as a pioneer in the design and use of combined and polyvalent vaccines. In the light of existing data, while acting as Director of the Bacteriological Institute of Colombo (Ceylon) in the decade before the First World War, Castellani was the first to experiment with both different strains of "antigens belonging to the same group" like in his typhoid-paratyphoid vaccine (TAB), as well as the simultaneous use of more pathogens, or part of them, for protection against different diseases, like in his "tetravaccine" (TAB + cholera) and "pentavaccine" (TAB + cholera + Malta fever). At the beginning of the War, based on the results of thousands of vaccinations, he strongly maintained that those combined or mixed vaccines were harmless and effective. The Allied Armies became more and more interested in Castellani's methods. His TAB vaccine was extensively used among the soldiers and his contributions were largely acknowledged especially in the Anglo-Saxon world in the following years, when it was plainly stated that "to Castellani is due the credit of having first proposed, prepared, and used, combined vaccines". The path to widespread use of combination and polyvalent vaccines - which is usually dated back only to the late 1940s - was still long and winding. Castellani himself abandoned that field of research after the War and this is probably why that early history is nowadays often forgotten. [ABSTRACT FROM AUTHOR]

Bacterial infections cause huge losses in aquaculture and a wide range of health issues in humans. A vaccine is the most economical, efficient, and environment-friendly agent for protecting hosts against bacterial infections. This study aimed to identify broad, cross-protective antigens from the extracellular secretory proteome of the marine bacterium Vibrio alginolyticus. Of the 69 predicted extracellular secretory proteins in its genome, 16 were randomly selected for gene cloning to construct DNA vaccines, which were used to immunize zebrafish (Danio rerio). The innate immune response genes were also investigated. Among the 16 DNA vaccines, 3 (AT730_21605, AT730_22220, and AT730_22910) were protective against V. alginolyticus infection with 47–66.7% increased survival compared to the control, while other vaccines had lower or no protective effects. Furthermore, AT730_22220, AT730_22910, and AT730_21605 also exhibited cross-immune protective effects against Pseudomonas fluorescens and/or Aeromonas hydrophila infection. Mechanisms for cross-protective ability was explored based on conserved epitopes, innate immune responses, and antibody neutralizing ability. These results indicate that AT730_21605, AT730_22220, and AT730_22910 are potential polyvalent vaccine candidates against bacterial infections. Additionally, our results suggest that the extracellular secretory proteome is an antigen pool that can be used for the identification of cross-protective immunogens.

Aquatic animals are frequently threated by bacterial pathogens. The most economic and efficient protection against bacterial infection are through vaccine immunization. The various serotypes of the pathogens, such as Vibrios, hurdle the development of the vaccines, especially polyvalent vaccines. Here, we demonstrate that recombinant bacterial ghost is a good candidate for multivalent vaccine. By expressing PhiX174 gene E alone or co-expressing the gene E with two genes encoding outer membrane proteins (VP1667 and VP2369) in V. parahaemolyticus , we generated the recombinant V. parahaemolyticus ghosts VPG and rVPGs respectively. Fish immunized with either VPG or rVPG showed increased survival against the infection by either V. parahaemolyticus or V. alginolyticus , with a better protective effect by immunization with rVPG. Our furthermore studies show that rVPG stimulates stronger innate immune responses by increasing the expression of tnfα, il1β, il6, il8 and il10 as well as that of c3b , lyz , and tlr5, the key players linking the innate and adaptive immune responses upon microbial stimulation. In summary, VPG and rVPG can protect zebrafish against the infection from at least two Vibrio species, suggesting its potential value for further aquaculture vaccines development. • Expressing lysis geneE in V. parahaemolyticus efficiently produces bacterial ghosts. • VP ghosts protect zebrafish against two Vibrio species challenge. • Overexpression of two membrane proteins enhances VP ghosts immunoprotection. • Recombinant VP ghosts stimulate strong innate immune response of zebrafish. [ABSTRACT FROM AUTHOR]

This study aimed to examine the use of Streptococcus agalactiae polyvalent vaccine in tilapia broodstock and the effect of maternal immunity and resistance on their offspring against S. agalactiae strain. The broodstock was injected with polyvalent vaccine of S. agalactiae at a dose of 108 CFU per fish at 2nd gonadal maturity until spawning. Challenge test was carried out on the offspring at the 5, 10, 15 and 20 days after hatching using NK1, N17O, N14G, N3M, N4M strain respectively and combination of them. We observed immunological parameters in broodstock, eggs and larvae and relative per cent survival (RPS) of larvae after challenged with pathogenic S. agalactiae. The results showed that the leukocytes, phagocytic activity, respiratory burst, lysozyme activity and antibody levels of vaccinated broodstock had higher level compared with unvaccinated broodstock. The high level of the lysozyme activity, antibody levels and recombination activating gene 1 (RAG1) were also observed in eggs and larvae from vaccinated broodstock. Larvae produced from vaccinated broodstock when challenged with variety strain of pathogenic S. agalactiae had RPS value more than 50% until 20 days after hatching. In conclusion, polyvalent vaccine of S. agalactiae administrated in the broodstock could enhance immunity in the broodstock and protect their offspring from pathogenic S. agalactiae. [ABSTRACT FROM AUTHOR]

Botulism is an acute neuroparalytic affliction of the motor and autonomic neurons caused by the toxins produced from Clostridium botulinum and related bacterial strains. The botulinum neurotoxins, or BoNTs, consist of a phylogenetically diverse group of highly potent protein toxins. Current medical interventions for confirmed cases of botulism are limited to immediate administration of antitoxins and respiratory support. There is currently no licensed vaccine against botulism in the United States. The most widely distributed botulism vaccine was a pentavalent BoNT toxoid (PBT) against serotypes A-E administered until 2011 under an investigational new drug license. A binary vaccine composed of the recombinant, non-toxic, receptor binding domains (RBD) of serotypes/A1 and/B1 has completed a phase II clinical trial, but has yet to attain full licensure. We have previously published data demonstrating catalytically inactive, full length botulinum neurotoxin holoproteins (ciBoNT HPs) against serotypes/A1,/B1,/C1,/E1 and/F1 provide equivalent or superior potency against parental and dissimilar subtype toxins as compared the RBD vaccines. Here we describe the consistent potencies of the three independent lots each of ciBoNT/C1,/E1, and/F1 HPs against substantial monovalent challenges of the parental toxins. We also present data that a trivalent formulation of ciBoNT/C1,/E1 and/F1 (triCEF) maintains potency against both monovalent and polyvalent toxin challenges when stored as an adjuvanted vaccine at 4–8 °C for up to 2 years. • Consistent potency of three independent lots each of ciBoNT/C1,/E1 and/F1 vaccines. • A trivalent vaccine protects against both individual and combined toxin challenges. • A trivalent botulism vaccine stored at 4 °C maintains potency up to 2 years. • Receptor domain mutations increase safety index of atoxic BNT protein antigens. [ABSTRACT FROM AUTHOR]

Abstract The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.V.P.C.R.; B.A.S.M.; B.C.B; H.C.Q.; A.M.S.F.; E.S.L.; M.E.B.; C.S.M.; L.M.S.F., R.J.S.B.; and M.B.P.S. declare no conflict of interest., (© 2024 The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Amin Rani, Moin, Patil, Barketullah Robin, Zubair, Nawal, Sami, Morshed, Zhai, Xue, Hossain, Zheng, Abul Manchur and Islam.)

Two variants of the experimental polyvalent vaccine against viral diseases of poultry have been made. The authors tested two samples of the vaccine, performed its preclinical study and study of its immunogenic activity and specific humoral immune response in chickens, and determined its stability. After all studies, a conclusion has been made that polyvalent inactivated vaccine allows to simultaneously create immunity againstthe Newcastle disease, infectious bronchitis of chickens, egg drop syndrome, infectious bursal disease, rheoviral and metapneumoviral infection of chicken;the vaccine is harmless, avirulent and immunogenic for poultry. [ABSTRACT FROM AUTHOR]

Our previous studies demonstrated that molecular breeding via DNA shuffling directs the evolution of polyvalent vaccines with desired traits, which leads to generation of polyvalent ompA vaccines using Vibrio alginolyticus VA0764 primers. Here, we replaced VA0764 primers with Edwardsiella tarda ompA primers to generate new polyvalent ompA vaccines by DNA shuffling of the same five ompA genes from four species of bacteria E. tarda, V. parahaemolyticus, V. alginolyticus and Escherichia coli. We identified four polyvalent vaccine candidates from a eukaryotic expressing library E ompAs -FE containing 82 ompAs using active immune protection against V. alginolyticus and E. tarda . Furthermore, we explored mechanisms of polyvalent vaccine candidates by investigation of the innate immune response to these ompAs , and found that expression of IL-1β, IL-8, IL-15, COX-2, IFN-γ, TLR-1, TLR-3 and C3b genes was elevated as a characteristic feature of these polyvalent vaccine candidates. These results indicate that use of different primers to construct a DNA library selects new evolution of polyvalent vaccines with desired traits, and polyvalent ompA vaccines elicit high innate immune response. [ABSTRACT FROM AUTHOR]

Vaccines are the most economic, efficient and environment-friendly agents in protecting host against bacterial infection. In aquaculture, polyvalent vaccines targeting more than one bacterial specie are highly demanded due to the presence of various types of bacterial pathogens in farming environment. Here eighteen genes encoding outer membrane proteins of Vibrio parahaemolyticus were cloned and expressed. The expressed recombinant proteins were used for antiserum preparation. Passive and active immune protection of the antiserum and recombinant proteins was investigated in the zebrafish model. Two recombinant proteins, VP1667 and VP2369, showed effective immune protection against at least two genera of bacteria, Vibrio ( V. parahaemolyticus and V. alginolyticus ), Pseudomonas (P. fluorescens) or/and Aeromonas ( A. hydrophila ), and thereby are potential polyvalent vaccine candidates to defend against bacterial infection in fish farming. Furthermore, the mechanisms for the two polyvalent vaccines in triggering immune response were explored. Antiserum to VP1667 or VP2369 was not cross-reacted with P. fluorescens and A. hydrophila, whereas both recombinant proteins induced significant innate immune response. Comparatively, VP1667 stimulates stronger lymphokine and monokine, and VP2369 induces stronger humoral immune response, while both produce similar NF-κB, COX-2, TLR-1 and TLR-3 expression. Our results identify two polyvalent vaccines and demonstrate characteristics features of their cross-protection at the content of the innate immune response. [ABSTRACT FROM AUTHOR]

We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD). The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9). A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the CVCVA5 improved the serum and mucosal antibody levels, cytokine levels of the chickens given the univalent vaccine, and also improved serum antibody titers in bivalent and tetravalent vaccines. This has a potential as an improve vaccine.

The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response. [ABSTRACT FROM AUTHOR]

Molecular breeding via DNA shuffling directs the evolution of vaccines with desired traits. In the present study, polyvalent OmpA vaccines were generated by DNA shuffling of five ompA genes from four species of bacteria Vibrio parahaemolyticus, V. alginolyticus, Edwardsiella tarda and Escherichia coli. First, a new hybrid OmpA was constructed using VA0764 primers and used for construction of a prokaryotic expressing library P ompAs -FV containing 84 ompAs , which were validated by PCR and SDS/PAGE. Then, the 84 ompAs were used to construct a eukaryotic expressing library E ompAs -FV for preparing DNA vaccines. Third, extracellular bacterium V. alginolyticus challenge post active immunization using these DNA vaccines was carried out to identify genes with high immunoprotection. Among the 84 ompAs , 17 showed higher or equal immune protection against infection caused by V. alginolyticus than control VA0764. Finally, immune protection against infection caused by intracellular bacterium Edwardsiella tarda was assessed further using the top seven out of the 17 ompAs. This led to identification of three efficient polyvalent vaccines against infections caused by the extracellular bacterium V. alginolyticus and intracellular bacterium E. tarda. In addition, we sequenced genes for understanding mechanisms of the polyvalent vaccines, but association of immune protection with mutation of gene and amino acids is not determined. These results indicate that DNA shuffling is an efficient way to develop polyvalent vaccines against microbial infections. [ABSTRACT FROM AUTHOR]

Vaccination is one of the most effective and economic way to prevent infectious diseases in aquaculture. The development of effective vaccines, however, is still limited, especially for polyvalent vaccines, which are against multiple species. With this regard, identification of polyvalent protective immunogens, serving as polyvalent vaccines, became a key step in vaccine development. In the current study, 17 outer membrane proteins from Vibrio parahaemolyticus were identified as immunogens. Further, four of the 17 proteins including VP2309, VP0887, VPA0548 and VP1019 were characterized as efficiently protective immunogens against V. parahaemolyticus ' infection through passive and active immunizations in zebrafish. Importantly, these four proteins showed cross-protective capability against infections by Aeromonas hydrophila or/and Pseudomonas fluorescens , which shared similar epitopes with V. parahaemolyticus in homology of these proteins. Further investigation showed that the expression level of the four protective immunogens elevated in response to fish plasma in a dose-dependent manner. These results indicate that the four protective immunogens are polyvalent vaccine candidates in aquaculture. [ABSTRACT FROM AUTHOR]

A wide variety of bacterial infections is a major challenge in aquaculture. Development of polyvalent vaccines that can fight against as many pathogens as possible is especially necessary. The present study uses DNA shuffling to create a new hybrid OmpA with improved cross-protection against Vibrio alginolyticus and Edwardsiella tarda through the recombination of six OmpA genes from Vibrio parahaemolyticus, V. alginolyticus, E. tarda and Escherichia coli . Out of the 43 recombinant chimeras genes constructed using VA0764 primers, E ompAs -19 was demonstrated as an ideal polyvalent vaccine against infections caused V. alginolyticus and E. tarda . Compared with VA0764, OmpAs-19 had three mutations, which may be a molecular basis of E ompAs -19 as an efficient polyvalent vaccine against both V. alginolyticus and E. tarda infections. These results develop a polyvalent vaccine that prevents the infections caused by extracellular and intracellular bacteria. Thus, the present study highlights the way to develop polyvalent vaccines against microbial infections by DNA shuffling. [ABSTRACT FROM AUTHOR]

Keywords: allergic contact dermatitis; case report; chlorhexidine digluconate; meningococcal vaccine; polyvalent vaccine; vaccination EN allergic contact dermatitis case report chlorhexidine digluconate meningococcal vaccine polyvalent vaccine vaccination 354 355 2 08/16/21 20210901 NES 210901 Chlorhexidine is an antiseptic agent frequently used in medicine. Allergic contact dermatitis, case report, chlorhexidine digluconate, meningococcal vaccine, polyvalent vaccine, vaccination. [Extracted from the article]

Group A streptococcal (Streptococcus pyogenes) diseases remain a major public health problem in developing countries as well as in the indigenous populations of developed countries. In view of the large number of Group A streptococcal infections and the potential for sequelae such as rheumatic heart disease, control strategies including the development of an anti-streptococcal vaccine that is able to prevent infection and colonization is important. In this article, we discuss the epidemiology and strain variability of Group A streptococcus and how this is rendering vaccine development more challenging. We discuss vaccine strategies with a focus on the conserved region of the M protein and present a viewpoint for the impediments and the way forward. [ABSTRACT FROM PUBLISHER]

Previous epidemiological study showed that most of the porcine enterotoxin Escherichia coli (ETEC) strains harbor multiple enterotoxins but lack any of the fimbriae or non-fimbrial adhesion genes. Therefore, effective ETEC vaccines need to aim directly at all the enterotoxin antigens. The objective of this study was to evaluate the simultaneous immune effect of two live attenuated E. coli strains expressing LT-STa and LT-STb fusion immunogen, respectively. The results showed that both local mucosal and systemic immune responses against LT, STa, STb, and F41 were induced in BALB/c mice immunized orally with the recombinant E. coli strains ER- A and ER- B simultaneously. In addition, results of cellular immune responses showed that stimulation index (SI) values of immunized mice were significantly higher than control mice ( P < 0.05) and a marked shift toward type-2 helper T lymphocyte (Th 2) immunity. Moreover, the induced antibodies demonstrated neutralizing effects on LT, STa, and STb producing E. coli infection. These data indicated that the use of recombinant E. coli ER- A and ER- B could be a valuable strategy for future polyvalent vaccine development of ETEC. [ABSTRACT FROM AUTHOR]

Live attenuated vaccines are cost effective approach for preventing a broad range of infectious diseases, and thus are of great interest. However, immune-defects can predispose the patient to infections by the vaccine candidate itself. So far, few live vaccine candidates have been designed specifically for immune compromised individuals. Recently, we reported a new Salmonella Typhimurium Z234-vaccine strain (Periaswamy et al., PLoS ONE 2012;7:e45433), which was specifically attenuated in the NADPH-oxidase deficient host. In the present study, the Z234-vaccine strain was further engineered to express heterologous antigen ( Vibrio cholerae toxin antigen subunit-B, i.e. CtxB) with the intention of creating a vector for simultaneous protection against Cholera and Salmonellosis. The primary aim of this study was to ensure the expression of CtxB antigen by the recombinant vaccine strain Z234-pMS101. The antigen CtxB was expressed through Z234 as a fusion protein with N-terminal signal sequence of Salmonella outer protein (SopE), an effector protein from Salmonella under the control of SopE promoter. The CtxB-expressing plasmid construct pMS101 (pM968-pSopE-ctxB) was found to be stable both in vitro and in vivo . In an oral mouse infection model, the vaccine strain Z234-pMS101 efficiently colonized the host gut. The extent of protection was confirmed after challenging the immunized hosts with live V. cholerae . Vaccinated mice showed reduced gut colonization by V. cholerae . Further assessment of immunological parameters supported the possibility of conferring effective immune response by Z234-pMS101 vaccine strain. Overall, the Z234-pMS101 vaccine strain showed potential as a promising polyvalent vaccine candidate to protect against S . Typhimurium and V. cholerae infection simultaneously. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) caused by multiple enterovirus infections is a serious health threat to children in the Asia–Pacific region. This article reviews progresses in the development of vaccines for HFMD and discusses the need for polyvalent HFMD vaccines for conferring broad-spectrum protection. [ABSTRACT FROM AUTHOR]

In order to produce polyvalent vaccines based on single rVSV vector, we investigated the immunogenicity, antibody neutralizing activity, and antigenic determinant domain of Zaire Ebola's fragment MFL (aa 393-556) that contains furin site and internal fusion loop. Both the recombinant protein and the recombinant plasmid of fragment MFL elicited high levels of antibody, similar to those of Zaire Ebola GP (ZGP). The MFL fragment of ZGP also elicited high levels of neutralizing antibody and induced moderate cellular immune response in mice, as revealed by the proliferation and cytokine secretion of splenocytes. Through the analysis of the induction of neutralizing antibody by pVAX1-based recombinant plasmids that expressed truncated fragments of MFL, we found that the domain containing the internal fusion loop and the furin site was the major contributor of fragment MFL's immunogenicity. Furthermore, the rVSV-based bivalent vaccine expressing Sudan Ebola GP (SGP) and MFL fragment elicited efficient cross-immunity against ZGP and SGP with high levels of neutralizing antibody. Our results indicate that fragment MFL is an effective and novel antigen for the production of neutralizing antibody and polyvalent vaccines of Ebola virus. [ABSTRACT FROM AUTHOR]