RESUMO
Picornaviridae are non-enveloped ssRNA viruses that cause diseases such as poliomyelitis, hand-foot-and-mouth disease (HFMD), hepatitis A, encephalitis, myocarditis, and foot-and-mouth disease (FMD). Virus-like particles (VLPs) vaccines mainly comprise particles formed through the self-assembly of viral capsid proteins (for enveloped viruses, envelope proteins are also an option). They do not contain the viral genome. On the other hand, the nanoparticles vaccine (NPs) is mainly composed of self-assembling biological proteins or nanomaterials, with viral antigens displayed on the surface. The presentation of viral antigens on these particles in a repetitive array can elicit a strong immune response in animals. VLPs and NPs can be powerful platforms for multivalent antigen presentation. This review summarises the development of virus-like particle vaccines (VLPs) and nanoparticle vaccines (NPs) against picornaviruses. By detailing the progress made in the fight against various picornaviruses such as poliovirus (PV), foot-and-mouth disease virus (FMDV), enterovirus (EV), Senecavirus A (SVA), and encephalomyocarditis virus (EMCV), we in turn highlight the significant strides made in vaccine technology. These advancements include diverse construction methods, expression systems, elicited immune responses, and the use of various adjuvants. We see promising prospects for the continued development and optimisation of VLPs and NPs vaccines. Future research should focus on enhancing these vaccines' immunogenicity, stability, and delivery methods. Moreover, expanding our understanding of the interplay between these vaccines and the immune system will be crucial. We hope these insights will inspire and guide fellow researchers in the ongoing quest to combat picornavirus infections more effectively.
Assuntos
Nanopartículas , Infecções por Picornaviridae , Picornaviridae , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais , Animais , Vacinas Virais/imunologia , Infecções por Picornaviridae/veterinária , Infecções por Picornaviridae/prevenção & controle , Infecções por Picornaviridae/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Picornaviridae/imunologiaRESUMO
BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.
Assuntos
Hidróxido de Alumínio , Infecções por Caliciviridae , Vírus da Doença Hemorrágica de Coelhos , Vacinas Virais , Animais , Coelhos , Hidróxido de Alumínio/farmacologia , Hidróxido de Alumínio/administração & dosagem , Vírus da Doença Hemorrágica de Coelhos/imunologia , Vacinas Virais/imunologia , Infecções por Caliciviridae/veterinária , Infecções por Caliciviridae/prevenção & controle , Géis , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Ácidos Oleicos/farmacologia , Ácidos Oleicos/administração & dosagemRESUMO
Largemouth bass ranavirus (LMBV) causes disease outbreaks and high mortality at all stages of largemouth bass farming. Therefore, live vaccine development is critical for largemouth bass prevention against LMBV by immersion immunization. Herein, an attenuated LMBV strain with good immunogenicity, designated as LMBV-2007136, was screened from the natural LMBV strains bank through challenge assay and immersion immunization experiment. After determing the safe concentration range of LMBV-2007136, the minimum immunizing dose of immersion immunization was verified. When largemouth bass were vaccinated by immersion at the lowest concentration of 102.0 TCID50/mL, all of fish were survival post virulent LMBV challenge, and the relative percent survival (RPS) was 100 %. And the immune gene expression levels of IL-10, IL-12, IFN-γ, and IgM in the spleen and kidney post-vaccination were significantly up-regulated compared to the control group, but TNF-α expression showed no significant changes. The safety and efficacy of LMBV-2007136 at passages P8, P13, and P18 were futher assessed, and no death of largemouth bass was observed within 21 days post-immunization and RPS of three vaccination groups was 100 %, suggesting that the safety and efficacy of the attenuated strain at different passages was stable. Furthermore, in the virulence reversion test, the attenuated strain was propagated through 5 times in largemouth bass by intraperitoneal injection and no abnormality and mortality were observed, further proving the attenuated vaccine candidate LMBV-2007136 was safe. These results proved that LMBV-2007136 could be a promising candidate for a live vaccine to protect largemouth bass from LMBV disease.
Assuntos
Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Ranavirus , Vacinas Atenuadas , Vacinas Virais , Animais , Bass/imunologia , Ranavirus/imunologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/prevenção & controle , Infecções por Vírus de DNA/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/administração & dosagem , Imunização/veterinária , Imersão , Vacinação/veterináriaRESUMO
Pure, potent and efficacious vaccines could help in the control of Newcastle disease (ND). The present study was designed to evaluate the thermo-stability of a live-attenuated ND virus vaccine containing the Mukteswar strain and to genetically characterize the seed virus. Moreover, the presence of extraneous agents (Fowl adenovirus, Mycoplasma, Salmonella Pullorum, and Salmonella Gallinarum) was assessed using polymerase chain reactions (PCR) optimized for detection in a panel. The vaccine was evaluated for its potency and efficacy after storage at 4°C, 25°C and 37°C for 36, 48, 96 and 144 hours. A total of 100 commercial broiler chickens were randomly divided into six groups and immunized with the vaccine stored at specified temperatures for the given times. Blood samples were collected on days 0, 7, 14, 21 and 28 post-vaccination, sera were separated and antibody titers were assessed using hemagglutination inhibition (HI) assay. The data were analyzed by two-way analysis of variance (ANOVA) and multivariate analysis of variance (MANOVA). Reverse-transcription PCR targeting the F gene of Newcastle disease virus (NDV) and subsequent sequence analysis confirmed the presence of NDV in the vaccine seed (deposited to GenBank Acc. Nos. MK310260 and MK310261). Phylogenetic analysis revealed a close resemblance of the vaccine virus with other Avian Avulaviruses (NDV class II Genotype III viruses and more specifically with NDV Mukteswar vaccine strains), yet it was distinct from NDV class II Pakistani field isolates, which grouped into genotype XIII.2.1. The PCR testing confirmed that the vaccine was free from extraneous agents. The present study's findings propose an alternative rapid PCR-based method to evaluate the purity of NDV live vaccines. Together these data suggest that the tested vaccine is pure, potent and efficacious, yet continuous maintenance of the cold chain for vaccine storage is recommended to maintain its potency and efficacy.
Assuntos
Galinhas , Doença de Newcastle , Vírus da Doença de Newcastle , Doenças das Aves Domésticas , Vacinas Atenuadas , Vacinas Virais , Animais , Vacinas Virais/imunologia , Vírus da Doença de Newcastle/imunologia , Vacinas Atenuadas/imunologia , Doença de Newcastle/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Armazenamento de Medicamentos , Eficácia de VacinasRESUMO
Background: Infectious diseases such as peste des petits ruminants (PPRs), contagious caprine pleuropneumonia (CCPP), sheep and goat pox (SGPX), and pasteurellosis have considerable impacts on the optimal utilization of sheep and goat resources in Ethiopia. Immunization using multiple vaccines administered simultaneously has been suggested as a cost-effective and safe approach to controlling and preventing these diseases. Aim: The aim of this study was to assess the immunogenicity and safety of multiple vaccines administered simultaneously in goats. Methods: Sero-negative PPR, CCPP, SGPX, and Pasteurellosis goats were immunized with multiple vaccines. Goats vaccinated with a single vaccine against each disease served as a positive control. The immune response of the goats was assessed using serological tests, and any adverse effects were monitored. Results: The results of the present study showed that goats vaccinated with multiple vaccines exhibited a remarkable immune response against PPR, CCPP, and pasteurellosis. In contrast, they did not produce a protective immune response against sheep or goat pox. No adverse effects were observed with any of the vaccines. Conclusion: This study suggested that combined vaccines can be effective at inducing a protective immune response in goats. However, further research is needed to fully understand the immune response to combined vaccines.
Assuntos
Vacinas Bacterianas , Doenças das Cabras , Cabras , Peste dos Pequenos Ruminantes , Pleuropneumonia Contagiosa , Vacinas Virais , Animais , Doenças das Cabras/prevenção & controle , Doenças das Cabras/virologia , Doenças das Cabras/imunologia , Peste dos Pequenos Ruminantes/prevenção & controle , Peste dos Pequenos Ruminantes/imunologia , Pleuropneumonia Contagiosa/prevenção & controle , Pleuropneumonia Contagiosa/imunologia , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Vírus da Peste dos Pequenos Ruminantes/imunologia , Infecções por Poxviridae/veterinária , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/imunologia , Ovinos , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/imunologia , Etiópia , Capripoxvirus/imunologia , Feminino , MasculinoRESUMO
Background: Bovine respiratory disease (BRD) is a complex illness that impacts the respiratory system of domestic cattle, resulting in significant financial losses for the agriculture industry. Inactivated or modified live (MLV) pathogen vaccines are often used as a management tool to prevent and control BRD effectively. Aim: The purpose of this study is to assess the cell-mediated immune response (CMI) induced by two commercially available polyvalent vaccines, namely the MLV (cattle master gold FP) and the inactivated (CATTLEWIN-5K) vaccine. Methods: A total of 20 seronegative heifers against 4 BRD viruses, bovine alphaherpisvirus-1 (BoAHV-1), bovine viral diarrhea virus (BVDV BVDV-1: Pesti virus A; BVDV-2: Pesti virus B), bovine respiratory syncytial virus (BRSV) and bovine parainfluenza virus-3 (BPIV3) were chosen for this study. The heifers were divided into three groups. The first group (n = 6) received no vaccination and was kept as a control. The second and third groups (seven heifers each) were vaccinated twice with either an MLV or inactivated vaccine. The gene expression level of interleukin-6 (IL-6) and interferon-gamma (INF-γ) was measured using real-time quantitative polymerase chain reaction on the 7th, 14th, 21st, 28th, and 60th days post-vaccination. The results were compared with the control group to study the effectiveness of the vaccines. Results: There was an upregulation in the expression level of IL-6 and INF-γ in both MLV and inactivated vaccinated groups. The level of IL-6 mRNA expression was statistically increased from the 14th and 28th days post-vaccination in MLV and inactivated vaccine groups, respectively. The expression level of INF-γ increased significantly from the 2nd and 4th weeks post-vaccination in the MLV and inactivated vaccine groups, respectively. The mean expression level of IL-6 and INF-γ mRNAs was significantly higher in the MLV vaccine group than in the inactivated vaccine group at each examination time. Conclusion: Both investigated vaccines are efficient in stimulating CMI, particularly with the MLV vaccine showing a higher preponderance in IL-6 and INF-γ.
Assuntos
Imunidade Celular , Vacinas de Produtos Inativados , Vacinas Virais , Animais , Bovinos , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Feminino , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Complexo Respiratório Bovino/prevenção & controle , Complexo Respiratório Bovino/imunologia , Complexo Respiratório Bovino/virologiaRESUMO
A novel tick-borne orthonairovirus called the Yezo virus (YEZV), primarily transmitted by the Ixodes persulcatus tick, has been recently discovered and poses significant threats to human health. The YEZV is considered endemic in Japan and China. Clinical symptoms associated with this virus include thrombocytopenia, fatigue, headache, leukopenia, fever, depression, and neurological complications ranging from mild febrile illness to severe outcomes like meningitis and encephalitis. At present, there is no treatment or vaccine readily accessible for this pathogenic virus. Therefore, this research employed an immunoinformatics approach to pinpoint potential vaccine targets within the YEZV through an extensive examination of its structural proteins. Three structural proteins were chosen using specific criteria to pinpoint T-cell and B-cell epitopes, which were subsequently validated through interferon-gamma induction. Six overlapping epitopes for cytotoxic T-lymphocytes (CTL), helper T-lymphocytes (HTL), and linear B-lymphocytes (LBL) were selected to construct a multi-epitope vaccine, achieving a 92.29% coverage of the global population. These epitopes were then fused with the 50S ribosomal protein L7/L12 adjuvant to improve protection against international strains. The three-dimensional structure of the designed vaccine construct underwent an extensive evaluation through structural analysis. Following molecular docking studies, the YEZV vaccine construct emerged as a candidate for further investigation, showing the lowest binding energy (-78.7 kcal/mol) along with favorable physiochemical and immunological properties. Immune simulation and molecular dynamics studies demonstrated its stability and potential to induce a strong immune response within the host cells. This comprehensive analysis indicates that the designed vaccine construct could offer protection against the YEZV. It is crucial to conduct additional in vitro and in vivo experiments to verify its safety and effectiveness.
Assuntos
Biologia Computacional , Epitopos de Linfócito B , Epitopos de Linfócito T , Vacinas Virais , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/química , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Animais , Vacinas Virais/imunologia , Vacinas Virais/química , Humanos , Proteínas Estruturais Virais/imunologia , Proteínas Estruturais Virais/química , Camundongos , Linfócitos T Citotóxicos/imunologia , Simulação de Acoplamento Molecular , ImunoinformáticaRESUMO
African swine fever (ASF) is an acute infectious disease with a high mortality rate in both domestic and wild boars. Commercial vaccines or antiviral drugs for ASF were not available due to the complex diversity of the structure and genome of its pathogen African swine fever virus (ASFV). In recent years, there have been many reports on candidate strains of attenuated vaccines for ASFV. In this study, we obtained a recombinant virus named SY18ΔL60LΔCD2v by simultaneously deleting the L60L gene and CD2v gene from highly virulent strain SY18. In vitro, SY18ΔL60LΔCD2v displayed a decreased growth kinetic compared to that of parental SY18. In vivo, high doses (105 TCID50) of SY18ΔL60LΔCD2v can protect pigs (5/5) from attacks by the parental SY18 strain (102 TCID50). Low doses (102 TCID50) of SY18ΔL60LΔCD2v only protected 20% of pigs (1/5) from attacks by the parental SY18 strain (102 TCID50). The results indicated that the absence of these two genes in SY18 could induce protection against the homologous parental strain, and there were no obvious clinical symptoms or viremia. These results indicate that the SY18ΔL60LΔCD2v strain can serve as a new live attenuated vaccine candidate for the prevention and control of ASFV infection.
Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Deleção de Genes , Vacinas Atenuadas , Vacinas Virais , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/imunologia , Vírus da Febre Suína Africana/patogenicidade , Animais , Suínos , Febre Suína Africana/prevenção & controle , Febre Suína Africana/virologia , Febre Suína Africana/imunologia , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Virais/imunologia , Vacinas Virais/genética , Proteínas Virais/genética , Proteínas Virais/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Viremia/prevenção & controleRESUMO
Bovine herpesvirus type 1 (BoHV-1) establishes lifelong latency in trigeminal ganglionic (TG) neurons following intranasal and ocular infection in cattle. Periodically, the latent virus reactivates in the TG due to stress and is transported anterogradely to nerve endings in the nasal epithelium, where the virus replicates and sheds. Consequently, BoHV-1 is transmitted to susceptible animals and maintained in the cattle population. Modified live BoHV-1 vaccine strains (BoHV-1 MLV) also have a similar latency reactivation. Therefore, they circulate and are maintained in cattle herds. Additionally, they can regain virulence and cause vaccine outbreaks because they mutate and recombine with other circulating field wild-type (wt) strains. Recently, we constructed a BoHV-1 quadruple mutant virus (BoHV-1qmv) that lacks immune evasive properties due to UL49.5 and glycoprotein G (gG) deletions. In addition, it also lacks the gE cytoplasmic tail (gE CT) and Us9 gene sequences designed to make it safe, increase its vaccine efficacy against BoHV-1, and restrict its anterograde neuronal transport noted above. Further, we engineered the BoHV-1qmv-vector to serve as a subunit vaccine against the Rift Valley fever virus (BoHV-1qmv Sub-RVFV) (doi: 10.3390/v15112183). In this study, we determined the latency reactivation and nasal virus shedding properties of BoHV-1qmv (vector) and BoHV-1qmv-vectored subunit RVFV (BoHV-1qmv sub-RVFV) vaccine virus in calves in comparison to the BoHV-1 wild-type (wt) following intranasal inoculation. The real-time PCR results showed that BoHV-1 wt- but not the BoHV-1qmv vector- and BoHV-1qmv Sub-RVFV-inoculated calves shed virus in the nose following dexamethasone-induced latency reactivation; however, like the BoHV-1 wt, both the BoHV-1qmv vector and BoHV-1qmv Sub-RVFV viruses established latency, were reactivated, and replicated in the TG neurons. These results are consistent with the anterograde neurotransport function of the gE CT and Us9 sequences, which are deleted in the BoHV-1qmv and BoHV-1qmv Sub-RVFV.
Assuntos
Herpesvirus Bovino 1 , Mucosa Nasal , Neurônios , Gânglio Trigeminal , Ativação Viral , Latência Viral , Eliminação de Partículas Virais , Animais , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/fisiologia , Herpesvirus Bovino 1/imunologia , Bovinos , Mucosa Nasal/virologia , Gânglio Trigeminal/virologia , Neurônios/virologia , Deleção de Genes , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/genética , Vacinas Atenuadas/administração & dosagem , Replicação Viral , Doenças dos Bovinos/virologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/genética , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Vetores Genéticos/genética , Rinotraqueíte Infecciosa Bovina/virologia , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Rinotraqueíte Infecciosa Bovina/imunologia , Vacinas contra Herpesvirus/genética , Vacinas contra Herpesvirus/imunologiaRESUMO
Heartland virus (HRTV) is a single-stranded negative-sense RNA virus that infects human beings. Because there are no antiviral medications available to treat HRTV infection, supportive care management is used in cases of severe disease. Therefore, it has spurred research into developing a multi-epitope vaccine capable of providing effective protection against HRTV infection. A multi-epitope vaccine was created using a combination of immuno-informatics, molecular docking and molecular dynamics simulation in this investigation. The HRTV proteome was utilized to predict B-cell, T-cell (HTL and CTL), and IFN-epitopes. Following prediction, highly antigenic, non-allergenic and immunogenic epitopes were chosen, including 6 CTL, 8 HTL, and 5 LBL epitopes that were connected to the final peptide by AAY, GPGPG, and KK linkers, respectively. An adjuvant was introduced to the vaccine's N-terminal through the EAAAK linker to increase its immunogenicity. Following the inclusion of linkers and adjuvant, the final construct has 359 amino acids. The presence of B-cell and IFN-γ-epitopes validates the construct's acquired humoral and cell-mediated immune responses. To ensure the vaccine's safety and immunogenicity profile, its allergenicity, antigenicity, and various physicochemical characteristics were assessed. Docking was used to assess the binding affinity and molecular interaction between the vaccination and TLR-3. In silico cloning was used to confirm the construct's validity and expression efficiency. The results of these computer assays demonstrated that the designed vaccine is highly promising in terms of developing protective immunity against HRTV; nevertheless, additional in vivo and in vitro investigations are required to validate its true immune-protective efficiency.
Assuntos
Epitopos de Linfócito T , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Vacinas Virais , Humanos , Vacinas Virais/imunologia , Vacinas Virais/química , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/química , Biologia Computacional , Epitopos/imunologia , Epitopos/química , BunyaviridaeRESUMO
Limited knowledge exists on the quality of polyclonal antibody responses generated following Marburg virus (MARV) infection and its evolution in survivors. In this study, we evaluate MARV proteome-wide antibody repertoire longitudinally in convalescent phase approximately every six months for five years following MARV infection in ten human survivors. Differential kinetics were observed for IgM vs IgG vs IgA epitope diversity, antibody binding, antibody affinity maturation and Fc-receptor interaction to MARV proteins. Durability of MARV-neutralizing antibodies is low in survivors. MARV infection induces a diverse epitope repertoire with predominance against GP, VP40, VP30 and VP24 that persisted up to 5 years post-exposure. However, the IgM and IgA repertoire declines over time. Within MARV-GP, IgG recognize antigenic sites predominantly in the amino-terminus, wing domain and GP2-heptad repeat. Interestingly, MARV infection generates robust durable FcɣRI, FcɣRIIA and FcɣRIIIA IgG-Fc receptor interactions. Immunization with immunodominant MARV epitopes reveals conserved wing region between GP1 and GP2, induces neutralizing antibodies against MARV. These findings demonstrate that MARV infection generates a diverse, long-lasting, non-neutralizing, IgG antibody repertoire that perturbs disease by FcɣR activity. This information, along with discovery of neutralizing immunogen in wing domain, could aid in development of effective therapeutics and vaccines against Marburg virus.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Doença do Vírus de Marburg , Marburgvirus , Proteoma , Marburgvirus/imunologia , Humanos , Doença do Vírus de Marburg/imunologia , Doença do Vírus de Marburg/virologia , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/imunologia , Proteoma/imunologia , Feminino , Vacinas Virais/imunologia , Imunoglobulina G/imunologia , Masculino , Epitopos/imunologia , Adulto , Imunoglobulina M/imunologia , Pessoa de Meia-Idade , Estudos Longitudinais , Imunoglobulina A/imunologia , Desenvolvimento de Vacinas , Proteínas do Envelope Viral/imunologiaRESUMO
Introduction: Epstein-Barr virus (EBV) is an oncogenic human herpesvirus associated with ~350,000 cases of lymphoid and epithelial malignancies every year, and is etiologically linked to infectious mononucleosis and multiple sclerosis. Despite four decades of research, no EBV vaccine candidate has yet reached licensure. Most previous vaccine attempts focused on a single viral entry glycoprotein, gp350, but recent data from clinical and pre-clinical studies, and the elucidation of viral entry mechanisms, support the inclusion of multiple entry glycoproteins in EBV vaccine design. Methods: Here we generated a modified vaccinia Ankara (MVA)-vectored EBV vaccine, MVA-EBV5-2, that targets five EBV entry glycoproteins, gp350, gB, and the gp42gHgL complex. We characterized the genetic and translational stability of the vaccine, followed by immunogenicity assessment in BALB/c mice and rhesus lymphocryptovirus-negative rhesus macaques as compared to a gp350-based MVA vaccine. Finally, we assessed the efficacy of MVA-EBV5-2-immune rhesus serum at preventing EBV infection in human CD34+ hematopoietic stem cell-reconstituted NSG mice, under two EBV challenge doses. Results: The MVA-EBV5-2 vaccine was genetically and translationally stable over 10 viral passages as shown by genetic and protein expression analysis, and when administered to female and male BALB/c mice, elicited serum EBV-specific IgG of both IgG1 and IgG2a subtypes with neutralizing activity in vitro. In Raji B cells, this neutralizing activity outperformed that of serum from mice immunized with a monovalent MVA-vectored gp350 vaccine. Similarly, MVA-EBV5-2 elicited EBV-specific IgG in rhesus macaques that were detected in both serum and saliva of immunized animals, with serum antibodies demonstrating neutralizing activity in vitro that outperformed serum from MVA-gp350-immunized macaques. Finally, pre-treatment with serum from MVA-EBV5-2-immunized macaques resulted in fewer EBV-infected mice in the two challenge experiments than pretreatment with serum from pre-immune macaques or macaques immunized with the monovalent gp350-based vaccine. Discussion: These results support the inclusion of multiple entry glycoproteins in EBV vaccine design and position our vaccine as a strong candidate for clinical translation.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Macaca mulatta , Animais , Humanos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/prevenção & controle , Camundongos , Herpesvirus Humano 4/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Camundongos Endogâmicos BALB C , Vacinas de DNA/imunologia , Feminino , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vetores Genéticos/genética , Vaccinia virus/imunologia , Vaccinia virus/genéticaRESUMO
This study aimed to determine the effects of spray dried plasma (SDP) on growth performance, carcass traits, tibia quality, and hemagglutination inhibition titers in broilers fed two nutritional strategies with high or low nutrient density. In the study, 816 one-day-old Ross 308 male broiler chickens were divided into a 2 × 2 factorial arrangements consisting of four treatment groups with 12 replicates (17 birds/replicate) based on diets with high nutrient density (HND) or low nutrient density (LND) from d 0 to 42 and receiving either control or 1% SDP diets during d 0 to 10. The results showed that feed intake (FI) and body weight gain (BWG) were increased (P < 0.05) and feed conversion ratio (FCR) was significantly reduced (P = 0.003) for broilers fed HND diets from d 0 to 42. The inclusion of SDP increased the BWG (P < 0.001), FI (P < 0.001), and FCR (P < 0.05) during d 0 to 10 of broiler life but not effect of SDP was observed for the whole 0-42 d period. Carcass yield increased with HND (P < 0.001) and dietary SDP (P = 0.002). However, HND feeding significantly decreased liver (P < 0.001), bursa of Fabricius (P = 0.002), abdominal fat (P < 0.001), proventriculus (P < 0.001) and gizzard weight (P < 0.001), but increased heart weight (P = 0.013), although spleen weight remained unaffected (P > 0.05) on d 42. Tibial bone morphometric and mechanical properties improved (P < 0.05) with SDP supplementation, and bone ash, Ca, and P remained unaffected (P > 0.05) on d 14. With the exception at d 28 (P = 0.037), the antibody titer to ND virus was similar among all treatment groups (P > 0.05) at d 0, 14, and 42. In conclusion, HND diets improve performance of broilers during the whole period and SDP supplementation during starter phase improve performance at this period, but also increased carcass yield, and tibial quality. Therefore, inclusion of SDP in the starter diet could be a beneficial nutritional strategy to improve the health and production of broilers provided feeding strategies using various nutrient densities.
Assuntos
Ração Animal , Galinhas , Tíbia , Zea mays , Animais , Galinhas/imunologia , Galinhas/crescimento & desenvolvimento , Ração Animal/análise , Tíbia/metabolismo , Masculino , Aminoácidos/metabolismo , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Dieta/veterinária , Doença de Newcastle/prevenção & controle , Doença de Newcastle/imunologia , Glycine max , Plasma/metabolismo , Vírus da Doença de Newcastle/imunologia , Fenômenos Fisiológicos da Nutrição Animal , Suplementos Nutricionais , Aumento de Peso/efeitos dos fármacosRESUMO
As the most prevalent companion animal, cats are threatened by numerous infectious diseases and carry zoonotic pathogens such as Toxoplasma gondii and Bartonella henselae, which are the primary causes of human toxoplasmosis and cat-scratch disease. Vaccines play a crucial role in preventing and controlling the spread of diseases in both humans and animals. Currently, there are only three core vaccines available to prevent feline panleukopenia, feline herpesvirus, and feline calicivirus infections, with few vaccines available for other significant feline infectious and zoonotic diseases. Feline herpesvirus, a major component of the core vaccine, offers several advantages and a stable genetic manipulation platform, making it an ideal model for vaccine vector development to prevent and control feline infectious diseases. This paper reviews the technologies involved in the research and development of the feline herpesvirus vaccine vector, including homologous recombination, CRISPR/Cas9, and bacterial artificial chromosomes. It also examines the design and effectiveness of expressing antigens of other pathogens using the feline herpesvirus as a vaccine vector. Additionally, the paper analyzes existing technical bottlenecks and challenges, providing an outlook on its application prospects. The aim of this review is to provide a scientific basis for the research and development of feline herpesvirus as a vaccine vector and to offer new ideas for the prevention and control of significant feline infectious and zoonotic diseases.
Assuntos
Doenças do Gato , Vetores Genéticos , Animais , Gatos , Doenças do Gato/prevenção & controle , Doenças do Gato/imunologia , Doenças do Gato/virologia , Infecções por Herpesviridae/prevenção & controle , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Vacinas Virais/imunologia , Desenvolvimento de Vacinas , Humanos , Sistemas CRISPR-Cas , VaricellovirusRESUMO
Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Febre Lassa , Vírus Lassa , Vírus Lassa/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Coelhos , Anticorpos Antivirais/imunologia , Febre Lassa/imunologia , Febre Lassa/prevenção & controle , Epitopos/imunologia , Vacinas Virais/imunologia , Humanos , Mapeamento de Epitopos , Formação de Anticorpos/imunologiaRESUMO
The resurgence of the Nipah virus (NiV) in 2023 has raised concerns for another potentially severe pandemic, given its history of high mortality from previous outbreaks. Unfortunately, no therapeutics and vaccines have been available for the virus. This study used immunoinformatics and molecular modeling to design and evaluate a multi-epitope subunit vaccine targeting NiV. The designed vaccine construct aims to stimulate immune responses in humans and two other intermediate animal hosts of the virus-swine and equine. Using several epitope prediction tools, ten peptides that induced B-lymphocyte responses, 17 peptides that induced cytotoxic T-lymphocyte (CTL) responses, and 12 peptides that induced helper T-lymphocyte (HTL) responses were mapped from nine NiV protein sequences. However, the CTL and HTL-inducing peptides were reduced to ten and eight, respectively, following molecular docking and dynamics. These screened peptides exhibited stability with 30 common major histocompatibility complex (MHC) receptors found in humans, swine, and equine. All peptides were linked using peptide linkers to form the multi-epitope construct and various adjuvants were tested to enhance its immunogenicity. The vaccine construct with resuscitation-promoting factor E (RpfE) adjuvant was selected as the final design based on its favorable physicochemical properties and superior immune response profile. Molecular docking was used to visualize the interaction of the vaccine to toll-like receptor 4 (TLR4), while molecular dynamics confirmed the structural stability of this interaction. Physicochemical property evaluation and computational simulations showed that the designed vaccine construct exhibited favorable properties and elicited higher antibody titers than the six multi-epitope NiV vaccine designs available in the literature. Further in vivo and in vitro experiments are necessary to validate the immunogenicity conferred by the designed vaccine construct and its epitope components. This study demonstrates the capability of computational methodologies in rational vaccine design and highlights the potential of cross-species vaccination strategies for mitigating potential NiV threats.
Assuntos
Biologia Computacional , Infecções por Henipavirus , Vírus Nipah , Vacinas de Subunidades Antigênicas , Vacinas Virais , Vírus Nipah/imunologia , Animais , Vacinas de Subunidades Antigênicas/imunologia , Humanos , Infecções por Henipavirus/prevenção & controle , Infecções por Henipavirus/imunologia , Vacinas Virais/imunologia , Cavalos/imunologia , Simulação de Acoplamento Molecular , Suínos , Simulação por Computador , Vacinação , Epitopos de Linfócito T/imunologia , Modelos Moleculares , Linfócitos T Citotóxicos/imunologia , Receptor 4 Toll-Like/imunologia , Camundongos , Epitopos de Linfócito B/imunologia , Epitopos/imunologia , Epitopos/química , ImunoinformáticaRESUMO
Largemouth bass ranavirus (LMBV) seriously affects the development of largemouth bass (Micropterus salmoides) industry and causes huge economic losses. Oral vaccine can be a promising method for viral disease precaution. In this study, MCP2α was identified as a valuable epitope region superior to MCP and MCP2 of LMBV by neutralizing antibody experiments. Then, recombinant Lactobacillus casei expressing the fusion protein MCP2αC (MCP2α as antigen, C represents flagellin C from Aeromonas hydrophila as adjuvant) on surface was constructed and verified. Further, PLA microsphere vaccine loading recombinant MCP2αC L. casei was prepared. The PLA microspheres vaccine were observed by scanning electron microscopy and showed a smooth, regular spherical surface with a particle size distribution between 100 and 200 µm. Furthermore, we evaluated the tolerance of PLA-MCP2αC vaccine in simulated gastric fluid and simulated intestinal fluid, and the results showed that PLA-MCP2αC can effectively resist the gastrointestinal environment. Moreover, the protective effect of PLA-MCP2αC against LMBV was evaluated after oral immunization and LMBV challenge. The results showed that PLA-MCP2αC effectively up-regulated the activity of serum biochemical enzymes (T-SOD, T-AOC, LZM, complement C3) and induced the mRNA expression of representative immune genes (IL-1ß, TNF-α, IFN-γ, MHC-IIα, Mx, IgM) in spleen and head kidney tissues. The survival rate of largemouth bass vaccinated with PLA-MCP2αC increased from 24 % to 68 %. Meanwhile, PLA-MCP2αC inhibited the LMBV burden in spleen, head kidney and liver tissues and attenuated tissue damage in spleen. These results suggested that PLA-MCP2αC can be used as a candidate oral vaccine against LMBV infection in aquaculture.
Assuntos
Bass , Infecções por Vírus de DNA , Doenças dos Peixes , Lacticaseibacillus casei , Microesferas , Animais , Bass/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Lacticaseibacillus casei/imunologia , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/prevenção & controle , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Poliésteres/administração & dosagem , IridoviridaeRESUMO
Orf virus (ORFV) is an acute contact, epitheliotropic, zoonotic, and double-stranded DNA virus that causes significant economic losses in the livestock industry. The objective of this study is to design an immunoinformatics-based multi-epitope subunit vaccine against ORFV. Various immunodominant cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), and B-cell epitopes from the B2L, F1L, and 080 protein of ORFV were selected and linked by short connectors to construct a multi-epitope subunit vaccine. Immunogenicity was enhanced by adding an adjuvant ß-defensin to the N-terminal of the vaccine using the EAAAK linker. The vaccine exhibited a significant degree of antigenicity and solubility, without allergenicity or toxicity. The 3D formation of the vaccine was subsequently anticipated, improved, and verified. The optimized model exhibited a lower Z-score of -4.33, indicating higher quality. Molecular docking results demonstrated that the vaccine strongly binds to TLR2 and TLR4. Molecular dynamics results indicated that the docked vaccine-TLR complexes were stable. Immune simulation analyses further confirmed that the vaccine can induce a marked increase in IgG and IgM antibody titers, and elevated levels of IFN-γ and IL-2. Finally, the optimized DNA sequence of the vaccine was cloned into the vector pET28a (+) for high expression in the E.coli expression system. Overall, the designed multi-epitope subunit vaccine is highly stable and can induce robust humoral and cellular immunity, making it a promising vaccine candidate against ORFV.
Assuntos
Epitopos de Linfócito B , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Vírus do Orf , Vacinas de Subunidades Antigênicas , Vacinas Virais , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/genética , Vacinas de Subunidades Antigênicas/química , Animais , Vírus do Orf/imunologia , Vírus do Orf/genética , Vacinas Virais/imunologia , Vacinas Virais/química , Vacinas Virais/genética , Camundongos , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/química , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/química , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/química , Ectima Contagioso/prevenção & controle , Ectima Contagioso/imunologia , Ectima Contagioso/virologia , Camundongos Endogâmicos BALB C , Feminino , Linfócitos T Citotóxicos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologiaRESUMO
The chicken immune system and microbiota play vital roles in maintaining gut homeostasis and protecting against pathogens. In mammals, XCR1+ conventional dendritic cells (cDCs) are located in the gut-draining lymph nodes and play a major role in gut homeostasis. These cDCs sample antigens in the gut luminal contents and limit the inflammatory response to gut commensal microbes by generating appropriate regulatory and effector T-cell responses. We hypothesized that these cells play similar roles in sustaining gut homeostasis in chickens, and that chickens lacking XCR1 were likely to contain a dysbiotic caecal microbiota. Here we compare the caecal microbiota of chickens that were either heterozygous or homozygous XCR1 knockouts, that had or had not been vaccinated for infectious bronchitis virus (IBV). We used short-read (Illumina) and long-read (PacBio HiFi) metagenomic sequencing to reconstruct 670 high-quality, strain-level metagenome assembled genomes. We found no significant differences between alpha diversity or the abundance of specific microbial taxa between genotypes. However, IBV vaccination was found to correlate with significant differences in the richness and beta diversity of the microbiota, and to the abundance of 40 bacterial genera. In conclusion, we found that a lack of XCR1 was not correlated with significant changes in the chicken microbiota, but IBV vaccination was.
Assuntos
Ceco , Galinhas , Microbioma Gastrointestinal , Vírus da Bronquite Infecciosa , Animais , Galinhas/microbiologia , Vírus da Bronquite Infecciosa/imunologia , Vírus da Bronquite Infecciosa/genética , Ceco/microbiologia , Vacinação , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Receptores Acoplados a Proteínas G/genética , Metagenoma , Células Dendríticas/imunologia , Bactérias/classificação , Bactérias/genética , MetagenômicaRESUMO
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic disease affecting camels and humans. The live attenuated vaccine represents a candidate human vaccine because it can induce strong immune responses in immunized hosts. The attenuated vaccine strain of the highly pathogenic virus can also be used to produce a cell-based vaccine in the BSL2 GMP facility. In this study, we evaluated the reversion potential of pathogenicity to pathogenic wild-type virus to ensure the safety of the live attenuated vaccine strain. We passaged our previously developed cold-adapted live attenuated MERS-CoV vaccine strain at 22 °C (EMC2012-CA22°C) in Vero cells at 37 °C as often as 15 times to determine the potential of pathogenicity reversion in hDPP4 (human dipeptidyl peptidase 4)-transgenic mice, K18-hDPP4. The serial passage of EMC2012-CA22°C in Vero cells at 37 °C up to 15 times did not result in pathogenicity reversion to wild-type MERS-CoV. In K18-hDPP4 mice infected with this virus, no weight loss or mortality was observed, and no virus was detected in tissues such as the lung, kidney, brain, and nasal turbinate. In addition, mice immunized with this virus produced a robust neutralizing antibody response and were fully protected from lethal challenge with wild-type MERS-CoV. The cold-adapted attenuated MERS-CoV vaccine strain (EMC2012-CA22°C) was not reverted to wild-type pathogenic virus after 15 passages in Vero cells at 37 °C.