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1.
Front Immunol ; 12: 718895, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512642

RESUMO

Background: Efficacy of vaccines and disease activity linked to immunization are major concerns among people with multiple sclerosis (pwMS). Objective: To assess antibody responses to seasonal influenza antigens and vaccine-associated neuroaxonal damage utilizing serum neurofilament light chain (sNfL) in pwMS receiving dimethyl fumarate (DMF). Methods: In this prospective study, the 2020/2021 seasonal tetravalent influenza vaccine was administered to 20 pwMS treated with DMF and 15 healthy controls (HCs). The primary endpoints were responder rate of strain-specific antibody production (seroconversion or significant (4-fold) increase in influenza-antibody titers for ≥2/4 strains) at 30 days post-vaccination and changes in sNfL levels. Results: All patients treated with DMF fulfilled the responder criteria for immunization compared with 53% of the controls. However, higher proportions of HCs already had influenza-antibody titers ≥1:40 at baseline (53% vs. 41%, p = 0.174). sNfL levels were comparable among both groups at baseline and did not increase 34 days after vaccination. In addition, no clinical or radiological disease reactivation was found. Conclusion: DMF-treated patients mount an adequate humoral immune response to influenza vaccines. Within the limits of the small cohort investigated, our data suggest that influenza immunization is not associated with clinical or subclinical disease reactivation.


Assuntos
Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Esclerose Múltipla Recidivante-Remitente , Vacinas Combinadas/imunologia , Adulto , Anticorpos Antivirais/sangue , Fumarato de Dimetilo/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Soroconversão/fisiologia
2.
Front Immunol ; 12: 692937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497604

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) kills thousands of people worldwide every day, thus necessitating rapid development of countermeasures. Immunoinformatics analyses carried out here in search of immunodominant regions in recently identified SARS-CoV-2 unannotated open reading frames (uORFs) have identified eight linear B-cell, one conformational B-cell, 10 CD4+ T-cell, and 12 CD8+ T-cell promising epitopes. Among them, ORF9b B-cell and T-cell epitopes are the most promising followed by M.ext and ORF3c epitopes. ORF9b40-48 (CD8+ T-cell epitope) is found to be highly immunogenic and antigenic with the highest allele coverage. Furthermore, it has overlap with four potent CD4+ T-cell epitopes. Structure-based B-cell epitope prediction has identified ORF9b61-68 to be immunodominant, which partially overlaps with one of the linear B-cell epitopes (ORF9b65-69). ORF3c CD4+ T-cell epitopes (ORF3c2-16, ORF3c3-17, and ORF3c4-18) and linear B-cell epitope (ORF3c14-22) have also been identified as the candidate epitopes. Similarly, M.ext and 7a.iORF1 (overlap with M and ORF7a) proteins have promising immunogenic regions. By considering the level of antigen expression, four ORF9b and five M.ext epitopes are finally shortlisted as potent epitopes. Mutation analysis has further revealed that the shortlisted potent uORF epitopes are resistant to recurrent mutations. Additionally, four N-protein (expressed by canonical ORF) epitopes are found to be potent. Thus, SARS-CoV-2 uORF B-cell and T-cell epitopes identified here along with canonical ORF epitopes may aid in the design of a promising epitope-based polyvalent vaccine (when connected through appropriate linkers) against SARS-CoV-2. Such a vaccine can act as a bulwark against SARS-CoV-2, especially in the scenario of emergence of variants with recurring mutations in the spike protein.


Assuntos
Antígenos Virais/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , SARS-CoV-2/imunologia , Sequência de Aminoácidos/genética , Antígenos Virais/genética , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/uso terapêutico , Biologia Computacional , Proteínas do Nucleocapsídeo de Coronavírus/genética , Desenho de Fármacos , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Humanos , Fases de Leitura Aberta/genética , Fases de Leitura Aberta/imunologia , SARS-CoV-2/genética , Análise de Sequência de Proteína , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
3.
BMC Infect Dis ; 21(1): 650, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225650

RESUMO

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common illness in young children. A monovalent vaccine has been developed in China protecting against enterovirus-71, bivalent vaccines preventing HFMD caused by two viruses are under development. OBJECTIVE: To predict and compare the incidence of HFMD under different vaccination scenarios in China. METHODS: We developed a compartmental model to capture enterovirus transmission and the natural history of HFMD in children aged 0-5, and calibrated to reported cases in the same age-group from 2015 to 2018. We compared the following vaccination scenarios: different combinations of monovalent and bivalent vaccine; a program of constant vaccination to that of pulse vaccination prior to seasonal outbreaks. RESULTS: We estimate 1,982,819, 2,258,846, 1,948,522 and 2,398,566 cases from 2015 to 2018. Increased coverage of monovalent vaccine from 0 to 80% is predicted to decrease the cases by 797,262 (49.1%). Use of bivalent vaccine at an 80% coverage level would decrease the cases by 828,560. Use of a 2.0× pulse vaccination for the bivalent vaccine in addition to 80% coverage would reduce cases by over one million. The estimated R0 for HFMD in 2015-2018 was 1.08, 1.10, 1.35 and 1.17. CONCLUSIONS: Our results point to the benefit of bivalent vaccine and using a pulse vaccination in specific months over routine vaccination. Other ways to control HFMD include isolation of patients in the early stage of dissemination, more frequent hand-washing and ventilation, and better treatment options for patients.


Assuntos
Enterovirus/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Pré-Escolar , China/epidemiologia , Feminino , Doença de Mão, Pé e Boca/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos , Vacinas Combinadas/imunologia
4.
BMC Vet Res ; 17(1): 186, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952269

RESUMO

BACKGROUND: Foot-and-mouth disease (FMD) and Haemorrhagic septicemia (HS) are two important diseases that are known to have caused significant economic losses to the cattle industry. Accordingly, vaccinations have been recognized as an efficient method to control and prevent both of the above-mentioned diseases. This study aimed to determine the immune response to FMD virus antigens and the recombinant outer membrane protein of HS (rOmpH) of Pasteurella multocida in cattle administered as a combination vaccine and compare antibody titers with the two vaccines given independently, under field conditions. Dairy cattle were divided into three groups. Each group was immunized with different vaccine types according to the vaccination program employed in this study. Antibody responses were determined by indirect ELISA, liquid phase blocking ELISA (LPB-ELISA) and viral neutralization test (VNT). Furthermore, the cellular immune responses were measured by lymphocyte proliferation assay (LPA). RESULTS: The overall antibody titers to HS and FMDV were above cut-off values for the combined FMD-HS vaccine in this study.The mean antibody titer against HS after the first immunization in the combined FMD-HS vaccine groups was higher than in the HS vaccine groups. However, no statistically significant differences (p > 0.05) were observed between groups. Likewise, the antibody titer to the FMDV serotypes O/TAI/189/87 and Asia 1/TAI/85 determined by LPB-ELISA in the combined vaccine were not statistically significantly different when compared to the FMD vaccine groups. However, the mean VNT antibody titer of combined vaccine against serotype O was significantly higher than the VN titer of FMD vaccine groups (p < 0.05). Moreover, the LPA results showed that all vaccinated groups displayed significantly higher than the negative control (p < 0.05). Nevertheless, no differences in the lymphocyte responses were observed in comparisons between the groups (p > 0.05). CONCLUSIONS: The combined FMD-HS vaccine formulated in this study could result in high both antibody and cellular immune responses without antigenic competition. Therefore, the combined FMD-HS vaccine can serve as an alternative vaccine against both HS and FMD in dairy cattle under field conditions.


Assuntos
Doenças dos Bovinos/imunologia , Febre Aftosa/imunologia , Septicemia Hemorrágica/imunologia , Vacinas Combinadas/imunologia , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Indústria de Laticínios/métodos , Feminino , Febre Aftosa/prevenção & controle , Vírus da Febre Aftosa , Septicemia Hemorrágica/prevenção & controle , Pasteurella multocida , Tailândia , Vacinação/veterinária
5.
Front Immunol ; 12: 592731, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33968011

RESUMO

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.


Assuntos
Antígenos/imunologia , Idade Gestacional , Imunidade , Recém-Nascido Prematuro/imunologia , Vacinas Combinadas/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Biomarcadores , Citocinas/sangue , Feminino , Humanos , Memória Imunológica , Imunofenotipagem , Índia/epidemiologia , Lactente , Recém-Nascido , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Vigilância em Saúde Pública , Vacinação
6.
Infect Immun ; 89(8): e0011521, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33941580

RESUMO

Comparative genomics of bacterial pathogens has been useful for revealing potential virulence factors. Escherichia coli is a significant cause of human morbidity and mortality worldwide but can also exist as a commensal in the human gastrointestinal tract. With many sequenced genomes, it has served as a model organism for comparative genomic studies to understand the link between genetic content and potential for virulence. To date, however, no comprehensive analysis of its complete "virulome" has been performed for the purpose of identifying universal or pathotype-specific targets for vaccine development. Here, we describe the construction of a pathotype database of 107 well-characterized completely sequenced pathogenic and nonpathogenic E. coli strains, which we annotated for major virulence factors (VFs). The data are cross referenced for patterns against pathotype, phylogroup, and sequence type, and the results were verified against all 1,348 complete E. coli chromosomes in the NCBI RefSeq database. Our results demonstrate that phylogroup drives many of the "pathotype-associated" VFs, and ExPEC-associated VFs are found predominantly within the B2/D/F/G phylogenetic clade, suggesting that these phylogroups are better adapted to infect human hosts. Finally, we used this information to propose polyvalent vaccine targets with specificity toward extraintestinal strains, targeting key invasive strategies, including immune evasion (group 2 capsule), iron acquisition (FyuA, IutA, and Sit), adherence (SinH, Afa, Pap, Sfa, and Iha), and toxins (Usp, Sat, Vat, Cdt, Cnf1, and HlyA). While many of these targets have been proposed before, this work is the first to examine their pathotype and phylogroup distribution and how they may be targeted together to prevent disease.


Assuntos
Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Genoma Bacteriano , Genômica , Animais , Vacinas Bacterianas/imunologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli/genética , Escherichia coli Extraintestinal Patogênica/genética , Genes Bacterianos , Humanos , Vacinas Combinadas/imunologia , Virulência/genética , Fatores de Virulência/genética
7.
Vet Microbiol ; 257: 109076, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33957572

RESUMO

The Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic zoonotic disease, which is potentially fatal in human with mortality rates ranging from 16.2%-32%. The rabies virus (RABV) LBNSE vector expressing foreign antigens have shown considerable promise as vaccines against viral diseases, which is effective and safe. In the present study, we generated a recombinant RABV rLBNSE-Gn expressing a SFTSV glycoprotein Gn by reverse genetic technology to control rabies and SFTS in animals. An extra insertion of Gn gene did not impact replication of the recombinant virus rLBNSE-Gn in NA and BHK-21 cells compared to the parent rLBNSE strain. The SFTSV Gn gene together with RABV N and G genes were efficiently expressed in rLBNSE-infected Vero cells by immunostaining and immune blots. A single dose of 107 FFU of the rLBNSE-Gn intramuscularly inoculated in BALB/c mice induced rapid and robust humoral responses against both RABV and SFTSV without any signs of disease or weight loss. Compared to the rLBNSE and DMEM groups, the extra Gn expression contributed to the recruitments and/or activations of the dendritic cells and B cells from inguinal lymph nodes of BALB/c mice vaccinated with rLBNSE-Gn. The protective efficacy of rLBNSE-Gn against SFTSV in C57BL/6 mice was evaluated, and the virus loading in the spleens reduced to 10 TCID50/mg at 7 days post SFTSV infections, which indicated that the rLBNSE-Gn conferred efficacious protective immune responses from SFTSV in C57BL/6 mice. All the mice immunization with rLBNSE-Gn and rLBNSE survived after a lethal RABV challenge, suggesting a 100 % protection from RABV. Therefore, the rLBNSE-Gn would be a promising bivalent candidate vaccine against SFTS and rabies in animals.


Assuntos
Anticorpos Antivirais/sangue , Vetores Genéticos , Phlebovirus/imunologia , Vírus da Raiva/genética , Raiva/prevenção & controle , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Vacinas Virais/imunologia , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Phlebovirus/genética , Vacinas Antirrábicas/administração & dosagem , Vacinas Antirrábicas/imunologia , Vírus da Raiva/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética
8.
Vet Immunol Immunopathol ; 237: 110256, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33971523

RESUMO

Lawsonia intracellularis is an economically important bacterium that causes ileitis in pigs. Current vaccines for L. intracellularis do not allow for differentiation between infected and vaccinated animals (DIVA), which is beneficial for disease tracking and surveillance. Previously, we identified five putative surface L. intracellularis proteins that were targeted by antibodies from pigs infected with L. intracellularis which could serve as antigens in a subunit vaccine. We conducted two trials to determine whether these antigens were immunogenic and provided protection against infectious challenge and whether truncated glycoprotein D could be used as a DIVA antigen. For Trial 1, 5 week-old piglets were administered intramuscular monovalent vaccines comprised of a recombinant (r) flagella subunit protein (rFliC,) and DIVA antigen (truncated glycoprotein D (TgD), a herpes virus antigen) both formulated with a combination adjuvant consisting of polyinosinic:polycytidylic acid(poly I:C), host defense peptide 1002 and polyphosphazene, referred to as Triple Adjuvant (TriAdj). Relative to control animals, animals vaccinated with rFliC and rTgD had significantly elevated antigen-specific humoral immunity in sera suggesting that rFliC and TgD are immunogenic. Control animals had negligible anti-TgD titres suggesting that TgD may be a suitable DIVA antigen for pigs. For Trial 2, piglets were immunized with a trivalent vaccine (FOG vaccine consisting of rFLiC, rOppA protein (a ABC Type dipeptide transport system) and rGroEL (a stress response protein)) and a divalent vaccine (CM vaccine consisting of rClpP (an ATP-dependent Clp protease proteolytic subunit) and rMetK (a S-adenosyl methionine synthase)) formulated with Emulsigen®. Relative to the control pigs, pigs immunized with the FOG vaccine produced robust and significantly higher serum IgG antibodies against rFliC and rGroEL, and significantly higher anti-FliC and anti-GroEL IgA antibodies in jejunal (GroEL only) and ileal intestinal mucosa. Pigs immunized with CM vaccine produced significantly higher serum antibodies against rClpP and rMetK and significantly higher anti-rClpP IgA antibodies in the ileum relative to the control pigs. Quantitative polymerase chain reaction (qPCR) analysis showed that 18 days after challenge with infectious L. intracellularis, challenged/control pigs and pigs that received the CM vaccine, but not the pigs vaccinated with the FOG vaccine, shed significantly more bacteria in feces than the unchallenged controls pigs. These data suggest that the FOG vaccinated pigs showed limited protection. While promising, more work is needed to enhance the efficiency of the intramuscular vaccine to show significant disease protection.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Desulfovibrionaceae/prevenção & controle , Imunogenicidade da Vacina , Lawsonia (Bactéria)/imunologia , Doenças dos Suínos/prevenção & controle , Animais , Animais Recém-Nascidos , Anticorpos Antibacterianos/imunologia , Infecções por Desulfovibrionaceae/imunologia , Feminino , Gravidez , Suínos , Doenças dos Suínos/microbiologia , Vacinas Combinadas/imunologia , Vacinas de Subunidades/imunologia
9.
Parasit Vectors ; 14(1): 241, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962671

RESUMO

BACKGROUND: Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually. METHODS: A chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays. RESULTS: When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens. CONCLUSIONS: There was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.


Assuntos
Vacinas Antimaláricas/administração & dosagem , Malária/prevenção & controle , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium berghei/imunologia , Proteínas de Protozoários/administração & dosagem , Vacinas Combinadas/administração & dosagem , Animais , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imunização , Malária/sangue , Malária/parasitologia , Malária/transmissão , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
10.
Commun Biol ; 4(1): 597, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011948

RESUMO

The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns. Here, we engineered the coat protein of the MS2 bacteriophage and generated nanoparticles displaying multiple copies of the SARS-CoV-2 spike (S) protein. The use of these nanoparticles as vaccines generated high neutralizing antibody titers and protected Syrian hamsters from a challenge with SARS-CoV-2 after a single immunization with no infectious virus detected in the lungs. This nanoparticle-based vaccine platform thus provides protection after a single immunization and may be broadly applicable for protecting against SARS-CoV-2 and future pathogens with pandemic potential.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Vacinas contra COVID-19/genética , Vacinas contra COVID-19/imunologia , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Imunização/métodos , Levivirus/genética , Levivirus/imunologia , Mesocricetus , Microscopia Eletrônica de Transmissão , Modelos Animais , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Nanotecnologia , Pandemias/prevenção & controle , Engenharia de Proteínas , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/administração & dosagem , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia
11.
Epidemiol Infect ; 149: e90, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33814028

RESUMO

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.


Assuntos
Infecções Meningocócicas/prevenção & controle , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antivirais/sangue , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/imunologia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/imunologia , Humanos , Imunogenicidade da Vacina , Lactente , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Segurança , Sorogrupo , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
12.
Helicobacter ; 26(3): e12807, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33847026

RESUMO

BACKGROUND: As the resistance of Helicobacter pylori to traditional triple therapy is gradually revealed, an increasing number of people are focusing on vaccine treatments for H. pylori infection. Epitope vaccines are a promising strategy for the treatment of H. pylori infection, and multivalent vaccines will be more effective than monovalent vaccines. MATERIALS AND METHODS: In this study, we designed a multivalent vaccine named LHUC, which consists of the adjuvant LTB as well as three Th cell epitopes (HpaA154-171 , UreB237-251, and UreB546-561 ) and five B-cell epitopes (UreB349-363 , UreB327-334 , CAT394-405 , CAT387-397, and HpaA132-141 ) from UreB, HpaA, and catalase. In BALB/c mice, the specificity and immunogenicity of the fusion peptide LHUC and the neutralization of H. pylori urease and catalase by the specific IgG elicited by LHUC were evaluated. The preventive and therapeutic effects of LHUC were evaluated in C57BL/6 mice infected with H. pylori. RESULTS: The results showed that compared with LTB and PBS, LHUC induced specific IgG and IgA antibody production in mice, and IgG antibodies significantly inhibited the H. pylori urease and catalase activities in vitro. Additionally, by detecting the levels of IFN-γ, IL-4, and IL-17 in lymphocyte supernatants, we proved that LHUC could activate Th1, Th2, and Th17 mixed T-cell immune responses in vivo. Finally, a C57BL/6 mouse model of gastric infection with H. pylori was established. The results showed that compared with the effects of LTB and PBS, the prevention and treatment effects of oral inoculation with LHUC significantly inhibited bacterial colonization. CONCLUSIONS: In conclusion, LHUC, a multivalent vaccine based on multiple H. pylori antigens, is a promising and safe vaccine that can effectively reduce the colonization of H. pylori in the stomach.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Helicobacter , Animais , Anticorpos Antibacterianos/imunologia , Epitopos de Linfócito T/imunologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Urease , Vacinas Combinadas/imunologia
13.
Infect Immun ; 89(7): e0010621, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-33875477

RESUMO

There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrhea for children in developing countries and international travelers. Virulence heterogeneity among strains and difficulties identifying safe antigens for protective antibodies against STa, a potent but poorly immunogenic heat-stable toxin which plays a key role in ETEC diarrhea, are challenges in ETEC vaccine development. To overcome these challenges, we applied a toxoid fusion strategy and a novel epitope- and structure-based multiepitope fusion antigen (MEFA) vaccinology platform to construct two chimeric multivalent proteins, toxoid fusion 3xSTaN12S-mnLTR192G/L211A and adhesin CFA/I/II/IV MEFA, and demonstrated that the proteins induced protective antibodies against STa and heat-labile toxin (LT) produced by all ETEC strains or the seven most important ETEC adhesins (CFA/I and CS1 to CS6) expressed by the ETEC strains causing 60 to 70% of diarrheal cases and moderate to severe cases. Combining two proteins, we prepared a protein-based multivalent ETEC vaccine, MecVax. MecVax was broadly immunogenic; mice and pigs intramuscularly immunized with MecVax developed no apparent adverse effects but had robust antibody responses to the target toxins and adhesins. Importantly, MecVax-induced antibodies were broadly protective, demonstrated by significant adherence inhibition against E. coli bacteria producing any of the seven adhesins and neutralization of STa and cholera toxin (CT) enterotoxicity. Moreover, MecVax protected against watery diarrhea and provided over 70% and 90% protection against any diarrhea from an STa-positive or an LT-positive ETEC strain in a pig challenge model. These results indicated that MecVax induces broadly protective antibodies and prevents diarrhea preclinically, signifying that MecVax is potentially an effective injectable vaccine for ETEC. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) bacteria are a top cause of children's diarrhea and travelers' diarrhea and are responsible for over 220 million diarrheal cases and more than 100,000 deaths annually. A safe and effective ETEC vaccine can significantly improve public health, particularly in developing countries. Data from this preclinical study showed that MecVax induces broadly protective antiadhesin and antitoxin antibodies, becoming the first ETEC vaccine candidate to induce protective antibodies inhibiting adherence of the seven most important ETEC adhesins and neutralizing the enterotoxicity of not only LT but also STa toxin. More importantly, MecVax is shown to protect against clinical diarrhea from STa-positive or LT-positive ETEC infection in a pig challenge model, recording protection from antibodies induced by the protein-based, injectable, subunit vaccine MecVax against ETEC diarrhea and perhaps the possibility of intramuscularly administered protein vaccines for protection against intestinal mucosal infection.


Assuntos
Diarreia/microbiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/imunologia , Antígenos de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Diarreia/imunologia , Modelos Animais de Doenças , Epitopos/imunologia , Proteínas de Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/efeitos adversos , Camundongos , Proteínas Recombinantes de Fusão/imunologia , Suínos , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
14.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33807097

RESUMO

Enteric fever is a major global healthcare issue caused largely by Salmonella enterica serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically engineering the attenuated S. Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two S. Paratyphi A immunogenic elements: flagellin H:a and lipopolysaccharide (LPS) O:2. We first replaced the native S. Typhi fliC gene encoding flagellin with the highly homologous fliC gene from S. Paratyphi A using Xer-cise technology. Next, we replaced the S. Typhi rfbE gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O:2 LPS and prevent its conversion to O:9 through tyvelose epimerase activity. The resulting new strain, ZH9PA, incorporated these two genetic changes and exhibited comparable growth kinetics to the parental ZH9 strain. A formulation containing both ZH9 and ZH9PA strains together constitutes a new bivalent vaccine candidate that targets both S. Typhi and S. Paratyphi A antigens to address a major global healthcare gap for enteric fever prophylaxis. This vaccine is now being tested in a Phase I clinical trial (NCT04349553).


Assuntos
Bioengenharia , Vacinas contra Salmonella/imunologia , Salmonella typhi/imunologia , Febre Tifoide/prevenção & controle , Vacinas Combinadas/imunologia , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Flagelina/imunologia , Vetores Genéticos/genética , Humanos , Imunogenicidade da Vacina , Lipopolissacarídeos/imunologia , Camundongos , Vacinas contra Salmonella/administração & dosagem , Vacinas contra Salmonella/genética , Salmonella typhi/genética , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/genética
15.
Biomed Res Int ; 2021: 4923852, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816612

RESUMO

Background: Haemophilus influenzae (H. influenzae) strains, which commonly reside as commensals within the human pharynx and can remain as an asymptomatic carrier, but become invasive leading to pneumonia, septic arthritis, or meningitis. The Pentavac (pentavalent vaccine, manufactured by India, SII (DTwP-HepB-Hib)) was introduced to the Iranian National Immunization Plan in November 2014. The aim of this study is to investigate H. influenzae type b (Hib) carrier rate among children under 6 years old in Tehran. Methods: This cross-sectional study was performed on 902 children including vaccinated/unvaccinated in the age of 6 months to 6 years, in Tehran. Sampling was performed from July 2019 to September 2019. Nasopharyngeal samples were taken from children by sterile swab. The PCR method was used to extract DNA. Then, all H. influenzae isolates were initially confirmed by molecular tests. BexA was used to distinguish typeable H. influenzae strains from nontypeable Haemophilus influenzae (NTHi). Results: A total of 902 children were enrolled in the study: 452 were female (51%). H. influenzae carriage rate was 267 (29%), of that 150 samples (16.6%) were typeable. The nasopharyngeal Hib carrier rate in the children was 2.6% (24/902). 262 cases did not receive Hib vaccine. Analysis in nonnursery's children aged 4 to 6 (unvaccinated) years showed that the lower educational level of father, mother, and family number correlated with increased odds of colonization of children with Hib. Conclusion: Our findings showed a significant decrease (60%) in the overall Hib nasopharyngeal carriage in healthy children under six years after 5 years after the start of Hib vaccination.


Assuntos
Portador Sadio , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Infecções por Haemophilus , Vacinas Anti-Haemophilus/administração & dosagem , Haemophilus influenzae tipo b/imunologia , Nasofaringe , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacinação , Portador Sadio/imunologia , Portador Sadio/microbiologia , Portador Sadio/patologia , Portador Sadio/prevenção & controle , Criança , Pré-Escolar , Estudos Transversais , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/patologia , Infecções por Haemophilus/prevenção & controle , Vacinas Anti-Haemophilus/imunologia , Humanos , Lactente , Irã (Geográfico) , Masculino , Nasofaringe/imunologia , Nasofaringe/microbiologia , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia
16.
Fish Shellfish Immunol ; 113: 162-175, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33857622

RESUMO

Streptococcosis and motile aeromonad septicemia (MAS) are well-known diseases in tilapia culture, which cause mass mortality with significant economic losses. The development of feed-based bivalent vaccines in controlling these diseases has been initiated, however, the mechanisms of immunities and cross-protection in fish remain unclear. This study was conducted to assess the immuno-protective as well as the cross-protective efficacy of a newly developed feed-based bivalent vaccine against Streptococcus and Aeromonas infections in red hybrid tilapia. A total of five groups of fish were vaccinated orally through two different techniques; bivalent vaccine (inactivated Streptococcus iniae and Aeromonas hydrophila) sprayed on feed pellets (BS group); bivalent vaccine (inactivated S. iniae and A. hydrophila) incorporated in feed (BI group); monovalent inactivated S. iniae and A. hydrophila vaccine separately incorporated into feed as monovalent S. iniae (MS group) and monovalent A. hydrophila (MA group); and control group (without vaccine). The feed-based vaccine was delivered orally at 5% of body weight for five consecutive days. The booster doses were given in the same manner on weeks 2 and 6. Serum and skin mucus samples were collected to assess the IgM responses using indirect ELISA. The first administration of the feed-based vaccine stimulated the IgM levels that lasted until week 3, while the second booster ensured that the IgM levels remained high for a period of 16 weeks in the BI, MS and MA groups. The BI group developed a strong and significantly (P < 0.05) higher systemic and mucosal IgM responses against both S. iniae and A. hydrophila and also cross-protective antigen S. agalactiae and A. veronii compared to the BS and control groups. Quantitative real-time PCR results also showed that the relative expressions of IL-8, INF-γ and IgM in the BI immunized fish spleen, head kidney and hindgut exhibited various significant (P < 0.05) rising trends following both the vaccination and the challenge phase. On weeks 10, all fish were challenged through the intraperitoneal route, where relative percent survivals (RPS) of 82.22 ± 3.85% when challenged with S. iniae, 77.78 ± 3.85% when challenged with A. hydrophila and 77.78 ± 3.85% when co-challenged with both S. iniae and A. hydrophila were observed in the BI group, which were significantly higher (P < 0.05) compared to the other groups. The BI group also showed significantly (P < 0.05) higher partial cross-protections following challenges with S. agalactiae (RPS at 60.00 ± 6.67%) and A. veronii (RPS at 57.78 ± 7.70%). This study demonstrated that immunization with feed-based BI vaccine elicited immune responses that were capable of protecting red hybrid tilapia against streptococcosis and MAS.


Assuntos
Vacinas Bacterianas/imunologia , Ciclídeos/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Vacinas Combinadas/imunologia , Animais , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/veterinária , Vacinas Estreptocócicas/imunologia , Vacinas de Produtos Inativados/imunologia
17.
Viruses ; 13(3)2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673603

RESUMO

The emergence of multiple concurrent infectious diseases localized in the world creates a complex burden on global public health systems. Outbreaks of Ebola, Lassa, and Marburg viruses in overlapping regions of central and West Africa and the co-circulation of Zika, Dengue, and Chikungunya viruses in areas with A. aegypti mosquitos highlight the need for a rapidly deployable, safe, and versatile vaccine platform readily available to respond. The DNA vaccine platform stands out as such an application. Here, we present proof-of-concept studies from mice, guinea pigs, and nonhuman primates for two multivalent DNA vaccines delivered using in vivo electroporation (EP) targeting mosquito-borne (MMBV) and hemorrhagic fever (MHFV) viruses. Immunization with MMBV or MHFV vaccines via intradermal EP delivery generated robust cellular and humoral immune responses against all target viral antigens in all species. MMBV vaccine generated antigen-specific binding antibodies and IFNγ-secreting lymphocytes detected in NHPs up to six months post final immunization, suggesting induction of long-term immune memory. Serum from MHFV vaccinated NHPs demonstrated neutralizing activity in Ebola, Lassa, and Marburg pseudovirus assays indicating the potential to offer protection. Together, these data strongly support and demonstrate the versatility of DNA vaccines as a multivalent vaccine development platform for emerging infectious diseases.


Assuntos
Culicidae/virologia , Ebolavirus/imunologia , Vacinas Combinadas/imunologia , Vacinas de DNA/imunologia , África Ocidental , Animais , Anticorpos Antivirais/imunologia , Arenavirus do Novo Mundo/imunologia , Vírus da Dengue/imunologia , Epidemias , Feminino , Cobaias , Doença pelo Vírus Ebola/imunologia , Imunidade Humoral/imunologia , Imunização/métodos , Febre Lassa/imunologia , Marburgvirus/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Vacinação/métodos , Vacinas Virais/imunologia , Zika virus/imunologia , Infecção por Zika virus/imunologia
18.
Vet Microbiol ; 256: 109046, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33780805

RESUMO

Lumpy Skin Disease (LSD) and Bluetongue (BT) are the main ruminants viral vector-borne diseases. LSD is endemic in Africa and has recently emerged in Europe and central Asia as a major threat to cattle industry. BT caused great economic damage in Europe during the last decade with a continuous spread to other countries. To control these diseases, vaccination is the only economically viable tool. For LSD, only live-attenuated vaccines (LAVs) are commercially available, whilst for BT both LAVs and inactivated vaccines are available with a limited number of serotypes. In this study, we developed an inactivated, oil adjuvanted bivalent vaccine against both diseases based on LSDV Neethling strain and BTV4. The vaccine was tested for safety and immunogenicity on cattle during a one-year period. Post-vaccination monitoring was carried out by VNT and ELISA. The vaccine was completely safe and elicited high neutralizing antibodies starting from the first week following the second injection up to one year. Furthermore, a significant correlation (R = 0.9040) was observed when comparing VNT and competitive ELISA in BTV4 serological response. Following BTV4 challenge, none of vaccinated and unvaccinated cattle were registered clinical signs, however vaccinated cattle showed full protection from viraemia. In summary, this study highlights the effectiveness of this combined vaccine as a promising solution for both LSD and BT control. It also puts an emphasis on the need for the development of other multivalent inactivated vaccines, which could be greatly beneficial for improving vaccination coverage in endemic countries and prophylaxis of vector-borne diseases.


Assuntos
Vírus Bluetongue/imunologia , Bluetongue/prevenção & controle , Doença Nodular Cutânea/prevenção & controle , Vírus da Doença Nodular Cutânea/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Animais , Bluetongue/virologia , Bovinos , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Doença Nodular Cutânea/virologia , Masculino , Ovinos , Vacinação/veterinária , Vacinas Atenuadas/imunologia , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/imunologia , Viremia/veterinária
19.
J Virol ; 95(6)2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33408178

RESUMO

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.


Assuntos
Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinação/métodos , Vacinas Virais/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Chlorocebus aethiops , Modelos Animais de Doenças , Doença de Mão, Pé e Boca/virologia , Camundongos , Sorogrupo , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Células Vero , Carga Viral , Vacinas Virais/imunologia , Vírion/imunologia
20.
Int J Biol Macromol ; 173: 244-250, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33485888

RESUMO

Influenza A virus (IAV) occasionally cross-species transmission among humans, swine and avian. The ectodomain of matrix protein 2 (M2e) is highly conserved in IAV, and multi-copy M2e from different species are usually displayed on the surface of nanoparticles to improve immunogenicity and constitute universal IAV nanovaccines. In our previous study, three M2e were inserted into the C-terminal of Cap protein of porcine circovirus type 2 (PCV2) to form a universal nanovaccine that provides protection against PCV2 and different subtypes of IAV. However, M2e adopts at least two converted conformations, and the intermolecular linker of M2e enhances the conformational instability, which limits the recognition by B cell receptors and production of high-level antibodies. Here, we report that the permutation of M2e affects effectiveness of nanovaccines. Three M2e derived from humans, swine and avian IAV were inserted into the C-terminal of Cap protein to form nanovaccines. Immunoprotective effects of different M2e arrangements were explored in mice. Results showed that the M2e closest to the surface of nanoparticle induced the most efficient protection against IAV derived from corresponding species. The results will contribute to develop more effective PCV2 and universal IAV bivalent nanovaccines for pigs, as well as species-specific universal IAV vaccines.


Assuntos
Proteínas do Capsídeo/metabolismo , Circovirus/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Receptores de Antígenos de Linfócitos B/metabolismo , Proteínas da Matriz Viral/metabolismo , Animais , Aves , Proteínas do Capsídeo/química , Proteínas do Capsídeo/imunologia , Feminino , Humanos , Imunização , Vacinas contra Influenza/imunologia , Camundongos , Nanopartículas , Conformação Proteica , Domínios Proteicos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/imunologia , Suínos , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/imunologia , Proteínas da Matriz Viral/química , Proteínas da Matriz Viral/imunologia
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