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1.
Mol Immunol ; 116: 106-116, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31634814

RESUMO

Shigellosis is a severe diarrheal disease with high mortality and morbidity rate. Until now, there is no approved vaccine against the disease. Therefore, the present study was planned to design a novel multi-epitope vaccine against Shigella spp., the causative agents of the disease based on the immunoinformatic tools. For this end, firstly seven conserved antigens of the bacteria, including IpaA, IpaB, IpaC, IpaD, OmpC, OmpF and VirG were selected. Then, linear B-cell epitope mapping of these proteins was carried out and top-ranked and shared epitopes were selected based on antigenicity, allergenicity, stability, toxicity and physicochemical properties for further analysis. In next step, B-cell derived T-cell epitopes were determined and appropriate epitopes were selected for incorporation into the final construct. Moreover, the selected epitopes and two mucosal adjuvants including ctxB and LT-IIc were joined using appropriate linkers. The three dimensional structure of the final construct was modeled and evaluated in term of structural quality and presence of conformational B-cell epitopes. Furthermore, binding affinity of the proposed vaccine to MHC I and II molecules were evaluated through molecular docking method using Hex 8.0. as well as the stability of the vaccine-MHC complexes was monitored by molecular dynamics method using the NAMD graphical user interface embedded in visual molecular dynamics. Finally, to evaluate the immunogenicity of the designed protein, the protein was administered to BALB/c mice and the serum IgG was determined by ELISA. The results indicated that the proposed vaccine has high structural quality and binding affinity to both MHC I and II molecules. Moreover, molecular dynamics studies confirmed that the vaccine-MHC docked complexes were stable during simulation time. Animal study showed that the proposed protein is able to evoke mice's humoral immune response. In sum, the results suggested that the proposed candidate vaccine could be considered as a promising anti-shigellosis vaccine.


Assuntos
Vacinas Bacterianas/imunologia , Proteção Cruzada/imunologia , Shigella/imunologia , Adjuvantes Imunológicos , Animais , Linfócitos B/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Imunidade Humoral/imunologia , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular/métodos , Vacinologia/métodos
2.
PLoS Negl Trop Dis ; 13(8): e0007601, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31374086

RESUMO

Genotype III (GIII) Japanese encephalitis virus (JEV) predominance has gradually been replaced by genotype I (GI) over the last 20 years in many Asian countries. This genotype shift raises concerns about the protective efficacy of Japanese encephalitis (JE) vaccines, as all of the currently licensed JE vaccines are derived from GIII strains. In this study, we conducted vaccination-challenge protection assays to evaluate the cross-protective efficacy of GI- or GIII-derived vaccines against the challenge of a heterologous genotype using a mouse challenge model. Titration of the neutralizing antibodies elicited by SA14-14-2 live-attenuated JE vaccine (SA14-14-2 vaccine), a GIII-derived vaccine, indicated that the titer of neutralizing antibodies specific to heterologous genotype GI stain was significantly lower than that specific to homologous genotype GIII strain in both pigs and mice immunized with the SA14-14-2 vaccine. Vaccination of mice with SA14-14-2 vaccine or a GIII-inactivated vaccine at high and medium doses completely protected vaccinated mice against challenge with the homologous genotype GIII strains, but failed to provide the vaccinated mice complete protection against the challenge of heterologous genotype GI strains. The protection rates against GI strain challenge were 60%-80%, showing that these vaccines were partially protective against GI strain challenge. Additionally, vaccination of mice with a GI-inactivated vaccine conferred 100% protection against the challenge of homologous genotype GI strains, but 50%-90% protection against the challenge of heterologous genotype GIII strains, showing a reduced protective efficacy of a GI-derived vaccine against GIII strain challenge. Overall, these observations demonstrated a partial cross-protection between GI and GIII strains and suggested a potential need for new JE vaccine strategies, including options like a bivalent vaccine, to control both genotype infection.


Assuntos
Proteção Cruzada/imunologia , Vírus da Encefalite Japonesa (Espécie)/genética , Vírus da Encefalite Japonesa (Espécie)/imunologia , Encefalite Japonesa/prevenção & controle , Genótipo , Vacinas contra Encefalite Japonesa/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Ásia , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência de Proteína , Suínos , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados
3.
Emerg Infect Dis ; 25(8): 1485-1493, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31075077

RESUMO

The Zika virus outbreak in Latin America resulted in congenital malformations, called congenital Zika syndrome (CZS). For unknown reasons, CZS incidence was highest in northeastern Brazil; one potential explanation is that dengue virus (DENV)-mediated immune enhancement may promote CZS development. In contrast, our analyses of historical DENV genomic data refuted the hypothesis that unique genome signatures for northeastern Brazil explain the uneven dispersion of CZS cases. To confirm our findings, we performed serotype-specific DENV neutralization tests in a case-control framework in northeastern Brazil among 29 Zika virus-seropositive mothers of neonates with CZS and 108 Zika virus-seropositive control mothers. Neutralization titers did not differ significantly between groups. In contrast, DENV seroprevalence and median number of neutralized serotypes were significantly lower among the mothers of neonates with CZS. Supported by model analyses, our results suggest that multitypic DENV infection may protect from, rather than enhance, development of CZS.


Assuntos
Proteção Cruzada/imunologia , Vírus da Dengue/imunologia , Dengue/imunologia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Brasil/epidemiologia , Dengue/epidemiologia , Dengue/história , Vírus da Dengue/classificação , Vírus da Dengue/genética , Feminino , História do Século XX , História do Século XXI , Humanos , Recém-Nascido , Filogenia , Gravidez , Prevalência , Vigilância em Saúde Pública , Sorogrupo , Fatores de Tempo , Infecção por Zika virus/história , Infecção por Zika virus/transmissão
4.
Nat Commun ; 10(1): 1660, 2019 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-30971703

RESUMO

Influenza A viruses evolve rapidly to escape host immunity, causing reinfection. The form and duration of protection after each influenza virus infection are poorly understood. We quantify the dynamics of protective immunity by fitting individual-level mechanistic models to longitudinal serology from children and adults. We find that most protection in children but not adults correlates with antibody titers to the hemagglutinin surface protein. Protection against circulating strains wanes to half of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that influenza antibody responses shift focus with age from the mutable hemagglutinin head to other epitopes, consistent with the theory of original antigenic sin, and might affect protection. Imprinting, or primary infection with a subtype, has modest to no effect on the risk of non-medically attended infections in adults.


Assuntos
Anticorpos Antivirais/sangue , Proteção Cruzada/imunologia , Memória Imunológica/imunologia , Influenza Humana/imunologia , Modelos Biológicos , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Antígenos Virais/isolamento & purificação , Criança , Pré-Escolar , Feminino , Seguimentos , Hemaglutininas/imunologia , Hong Kong/epidemiologia , Humanos , Incidência , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
5.
PLoS One ; 14(3): e0212927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30830913

RESUMO

BACKGROUND: HPV vaccination with the bivalent vaccine is efficacious against HPV16 and 18 infections and cross-protection against non-vaccine HPV types has been demonstrated. Here, we assessed (cross-) protective effects of the bivalent HPV16/18 vaccine on incident and persistent infections and viral load (VL) of fifteen HPV types in an observational cohort study monitoring HPV vaccine effects. METHODS: Vaginal samples were obtained annually. Type-specific VL assays were developed for HPV6,11,31 33,35,39,45,51,52,56,58,59 and 66 and used in addition to existing HPV16 and 18 assays. Rate differences of incident clearing and persistent infections were correlated with differences in VL and vaccination status. RESULTS: HPV16/18 vaccination resulted in significantly lower incidence of HPV16/18 infections and significantly lower VL in breakthrough HPV16 (p<0.01) and 18 infections (p<0.01). The effects of vaccination on non-vaccine type VL were ambiguous. Incidence and/or persistence rates of HPV31, 33, 35 and 45 were reduced in the vaccinated group. However, no significant type specific VL effects were found against HPV31, 33, 45, 52 in the vaccinated group. For HPV 6, 59 and 66 no significant reductions in numbers of incident and persistent infections were found, however borderline) VL reductions following vaccination were observed for HPV6 (p = 0.01), 59 (p = 0.10) and 66 (p = 0.03), suggesting a minor effect of the vaccine on the VL level of these HPV types. Overall, vaccination resulted in infections with slightly lower VL, irrespective of HPV type. CONCLUSIONS: In conclusion, vaccination with the bivalent HPV16/18 vaccine results in significantly reduced numbers of HPV16 and 18 incidence rates and reduced VL in breakthrough infections. Significant reductions in incident and/or persistent HPV31, 33, 35 and 45 infections were found, but no significant effect was observed on the VL for infections with these types. For the other non-vaccine HPV types no reduction in incident and/or persistent infections were found, but overall the VL tended to be somewhat lower in vaccinated women.


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinação/métodos , Carga Viral , Adolescente , Proteção Cruzada/imunologia , Feminino , Humanos , Países Baixos , Papillomaviridae/imunologia , Infecções por Papillomavirus/sangue , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Sorotipagem , Vagina/virologia
6.
Microbes Infect ; 21(8-9): 368-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30853357

RESUMO

Multiple diarrheagenic enteric bacterial infections cause global morbidity and mortality. A combination vaccine is needed to combat different diarrhea-causing organisms. In our present work, we formulated a combination of antigens from three different diarrheagenic Escherichia coli strains and three different Vibrio cholerae strains. We demonstrated that our newly formulated combination immunogen was able to raise species-specific immunogenicity. This formulation also gave protection against different diarrheagenic E. coli strains in the removable intestinal tie-adult rabbit diarrhea model. However, protective efficacy was not found against the V. cholerae El Tor Ogawa Haitian variant, but challenged with V. cholerae El Tor Inaba or O139 showed protection in rabbits. This is the first report of a single formulated nonliving heat-killed combination immunogen from different diarrheagenic E. coli and V. cholerae that could bestow protection against different bacteria in an animal model.


Assuntos
Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Diarreia/prevenção & controle , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/imunologia , Escherichia coli/imunologia , Vibrio cholerae/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Vacinas contra Cólera/administração & dosagem , Proteção Cruzada/imunologia , Diarreia/microbiologia , Modelos Animais de Doenças , Escherichia coli/genética , Vacinas contra Escherichia coli/administração & dosagem , Imunização , Imunoglobulinas/sangue , Coelhos , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/imunologia , Vibrio cholerae/genética
7.
Vet Microbiol ; 230: 278-282, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30827401

RESUMO

Although highly virulent GII-genotype PEDV strains have become pandemic in the swine population worldwide, little is known about the differences in immunogenicity and cross-protective efficacy between the GIIa and GIIb subgenotypes. Hence, in the present study, we vaccinated suckling piglets with GIIa (CH/HBXT/2018) and GIIb (CH/HNPJ/2017) PEDV strain-based inactivated vaccine candidates and compared their immunogenicity and cross-protective efficacy. The results showed that both vaccine candidates induced high levels of PEDV-specific IgG antibodies and IFN-γ and reduced the levels of neutralizing antibodies at 21 dpv in suckling piglets. The GIIa-based inactivated vaccine protected all piglets (8/8) against virulent homologous and heterologous virus challenge, while the GIIb strain-based inactivated vaccine protected only 2/4 and 1/4 piglets against virulent homologous and heterologous virus challenge, respectively. Furthermore, antibodies against the GIIa and GIIb strains cross-reacted and cross-neutralized both strains in vitro. Taken together, the data presented in this study indicate that GIIa strain-based inactivated vaccine candidates are more promising than GIIb-based candidates for the development of an effective vaccine against the current highly virulent pandemic PEDV strains.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Coronavirus/veterinária , Proteção Cruzada/imunologia , Imunogenicidade da Vacina , Doenças dos Suínos/prevenção & controle , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Técnicas de Cultura de Células , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Genótipo , Imunoglobulina G/sangue , Interferon gama/imunologia , Vírus da Diarreia Epidêmica Suína/genética , Vírus da Diarreia Epidêmica Suína/patogenicidade , Suínos , Doenças dos Suínos/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem , Eliminação de Partículas Virais
8.
J Infect Dis ; 219(12): 1913-1923, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-30722024

RESUMO

BACKGROUND: Few studies have evaluated the relative cross-protection conferred by infection with different groups of viruses through studies of sequential infections in humans. We investigated the presence of short-lived relative cross-protection conferred by specific prior viral infections against subsequent febrile respiratory illness (FRI). METHODS: Men enlisted in basic military training between December 2009 and December 2014 were recruited, with the first FRI as the study entry point. ResPlex II assays and real-time polymerase chain reaction assays were used to detect viral pathogens in nasal wash samples, and survival analyses were performed to determine whether infection with particular viruses conferred short-lived relative cross-protection against FRI. RESULTS: Prior infection with adenovirus (hazard ratio [HR], 0.24; 95% confidence interval [CI], .14-.44) or influenza virus (HR, 0.52; 95% CI, .38-.73) conferred relative protection against subsequent FRI episode. Results were statistically significant even after adjustment for the interval between enlistment and FRI (P < .001). Adenovirus-positive participants with FRI episodes tended to be protected against subsequent infection with adenovirus, coronavirus, enterovirus/rhinovirus, and influenza virus (P = .062-.093), while men with influenza virus-positive FRI episodes tended be protected against subsequent infection with adenovirus (P = .044) and influenza virus (P = .081). CONCLUSION: Prior adenovirus or influenza virus infection conferred cross-protection against subsequent FRI episodes relative to prior infection due to other circulating viruses.


Assuntos
Proteção Cruzada/imunologia , Infecções Respiratórias/imunologia , Viroses/imunologia , Vírus/imunologia , Feminino , Humanos , Masculino , Militares , Infecções Respiratórias/virologia , Singapura , Análise de Sobrevida , Viroses/virologia
9.
J Infect Dis ; 219(3): 448-458, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30165645

RESUMO

Background: Streptococcus suis is an encapsulated zoonotic pathogen. Increasing antimicrobial resistance invokes the need for effective vaccines. Despite many attempts to develop an effective vaccine, none is currently available. Methods: A capsular polysaccharide (CPS)-expressing attenuated mutant 2015033 was constructed by deleting 5 virulence-associated factors (sly, scpA, ssnA, fhb, and ssads) in an infective S. suis strain SC19. The safety and immune effect of 2015033 were determined both in vitro and in vivo. Results: Deletion of 5 genes did not impact the growth ability and CPS generation of 2015033, and the mutant exhibited no cytotoxicity in different cell models. 2015033 was more easily eliminated by innate immunity both in vitro and in vivo. In addition, 2015033 showed a diminished invasive ability in different mouse organs (brain, lung, and liver) and avirulent properties in mice associated with weak inflammation-inducing ability. Immunization with 2015033 triggered T cell-dependent immunity, suppressed streptococcal toxic shock-like syndrome, and conferred sequence type-independent protection to mice during infection. Conclusions: This study presents the feasibility of the strategy of multigene deletion for the development of promising live vaccines against invasive encapsulated pathogens.


Assuntos
Choque Séptico/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus suis/imunologia , Vacinas Atenuadas/imunologia , Animais , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/imunologia , Encéfalo/patologia , Células CACO-2 , Proteção Cruzada/imunologia , Modelos Animais de Doenças , Feminino , Deleção de Genes , Genes Bacterianos/genética , Humanos , Imunidade Inata , Imunização , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Choque Séptico/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Streptococcus suis/genética , Linfócitos T/imunologia , Vacinação , Virulência/genética , Fatores de Virulência/genética
10.
Poult Sci ; 98(1): 199-208, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30184142

RESUMO

Vaccines against avian influenza are mostly based on hemagglutinin (HA), which is the main antigen of this virus and a target for neutralizing antibodies. Traditional vaccines are known to be poorly efficient against newly emerging strains, which is an increasing worldwide problem for human health and for the poultry industry. As demonstrated by research and clinical data, sequential exposure to divergent influenza HAs can boost induction of universal antibodies which recognize conserved epitopes. In this work, we have performed sequential immunization of laying hens using monovalent or bivalent compositions of DNA vaccines encoding HAs from distant groups 1 and 2 (H5, H1, and H3 subtypes, respectively). This strategy gave promising results, as it led to induction of polyclonal antibodies against HAs from both groups. These polyclonal antibodies showed cross-reactivity between different HA strains in ELISA, especially when bivalent formulations were used for immunization of birds. However, cross-reactivity of antibodies induced against H3 and H5 HA subtypes was rather limited against each other after homologous immunization. Using a cocktail of HA sequences and/or sequential DNA vaccination with different strains presents a good strategy to overcome the limited effectiveness of vaccines and induce broader immunity against avian influenza. Such a strategy could be adapted for vaccinating laying hens or parental flocks of different groups of poultry.


Assuntos
Proteção Cruzada/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A/imunologia , Influenza Aviária/imunologia , Vacinas de DNA/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais , Galinhas , Feminino , Hemaglutininas , Influenza Aviária/prevenção & controle , Influenza Aviária/virologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Vacinação/veterinária
11.
J Infect Dis ; 219(3): 382-390, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30299519

RESUMO

Background: Proactive recommendations for human papillomavirus (HPV) vaccines in Japan have been suspended for 5 years because of safety concerns. While no scientific evidence exists to substantiate these concerns, one reason given for not reinstating recommendations is the lack of reliable vaccine effectiveness (VE) data in a Japanese population. This study reports the VE of the bivalent HPV vaccine in Japanese women aged 20-22 years. Methods: During cervical screening between 2014 and 2016, women had Papanicolaou smears and HPV tests performed and provided data about their sexual history. Estimates of VE for vaccine-targeted HPV type 16 (HPV16) and 18 and cross-protection against other types were calculated. Results: Overall, 2197 women were tested, and 1814 were included in the analysis. Of these, 1355 (74.6%) were vaccinated, and 1295 (95.5%) completed the 3-dose schedule. In women sexually naive at vaccination, the pooled VEs against HPV16 and 18 and for HPV31, 45, and 52 were 95.5% (P < .01) and 71.9% (P < .01), respectively. When adjusted for number of sex partners and birth year, pooled VEs were 93.9% (P = .01) and 67.7% (P = .01) for HPV16 and 18 and HPV31, 45, and 52, respectively. Conclusions: The bivalent HPV vaccine is highly effective against HPV16 and 18. Furthermore, significant cross-protection against HPV31, 45, and 52 was demonstrated and sustained up to 6 years after vaccination. These findings should reassure politicians about the VE of bivalent HPV vaccine in a Japanese population.


Assuntos
Proteção Cruzada/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Adulto , Colo do Útero/imunologia , Detecção Precoce de Câncer , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 31/imunologia , Humanos , Imunização , Programas de Imunização , Japão , Infecções por Papillomavirus/diagnóstico , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação , Adulto Jovem
12.
Fish Shellfish Immunol ; 85: 85-89, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29056488

RESUMO

Viral encephalopathy and retinopathy (VER) is a severe infective disease characterized by neuropathological changes in several fish species associated with high mortality. The etiological agent is a virus belonging to the Nodaviridae family, genus Betanodavirus. To date, four different betanodavirus species have been officially recognized by International Committee on Taxonomy of Viruses (ICTV), namely the red-spotted grouper- (RGNNV), the striped jack- (SJNNV), the barfin flounder- (BFNNV) and the tiger puffer nervous necrosis virus (TPNNV). Moreover, two reassortants RGNNV/SJNNV and SJNNV/RGNNV have been described. Betanodaviruses can be classified into three different serotypes (A, B and C) that are antigenically different, so none (between serotype A and C) or partial (between serotype B and C) cross-immunoreactivity has been detected in vitro. In this study we investigated the in vivo cross-protection of the two main betanodavirus species (RGNNV and SJNNV), which belong to distinct serotype, by immunizing intraperitoneally (IP) juvenile sea bass with formalin inactivated RGNNV and SJNNV vaccines, followed by a challenge with RGNNV. Fish IP vaccinated with inactivated RGNNV showed a high protection value (85%). Serological analyses highlighted a great specific anti-NNV immunoglobulin M (IgM) production against the homologous virus, while a good seroconversion with low neutralization property was highlighted against the heterologous virus. In fish IP vaccinated with inactivated SJNNV the protection recorded was equal to 25%, significantly lower respect to the one provided by RGNNV IP vaccine. ELISA test detected good IgM production against the homologous virus, and a lower, but still detectable IgM production against the heterologous one. By contrast, serum neutralization test highlighted a poorly detectable antibody production unable to neutralize either the homologous or the heterologous virus. These results confirm that the two serotypes are not cross-protective in vivo. According to these findings, the production of multivalent formulation, or at least the provision of different types of vaccines based on both fish and virus species requirement, should be recommended in order to broaden the range of protection.


Assuntos
Bass , Proteção Cruzada/imunologia , Doenças dos Peixes/prevenção & controle , Nodaviridae/imunologia , Infecções por Vírus de RNA/veterinária , Vacinação/veterinária , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Injeções Intraperitoneais/veterinária , Nodaviridae/classificação , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/prevenção & controle , Infecções por Vírus de RNA/virologia
13.
Immunobiology ; 224(2): 223-230, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30558842

RESUMO

Previously we reported that recombinant Chlamydia muridarum macrophage infectivity potentiator (MIP) provided partial protection against C. muridarum genital tract infection in mice. On the other hand, Chlamydia trachomatis plasmid encoded Pgp3could induce the protection against C. muridarum air way infection. This study aimed to evaluate the immunogenicity of MIP and Pgp3 from C. trachomatis serovar D and further investigate whether MIP and Pgp3 provide cross-serovar protection against C. muridarum genital tract infection in mice. Our results showed that vaccination by any regimen, including MIP alone, Pgp3 alone or MIP plus Pgp3, induced specific serum antibody production and Th1-dominant cellular responses in mice. Live chlamydial shedding from the vaginal and inflammatory pathologies in the oviduct markedly reduced. However, MIP + Pgp3 vaccination did not provide better protection than the single immunization. In conclusion, this study demonstrated that both MIP and Pgp3 can induce cross-serovar protective against chlamydial genital tract infection, and provided the guide for the development of optimal multisubunit vaccines against C. trachomatis infection.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Chlamydia/prevenção & controle , Proteção Cruzada/imunologia , Peptidilprolil Isomerase/imunologia , Doenças Bacterianas Sexualmente Transmissíveis/prevenção & controle , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Linhagem Celular , Infecções por Chlamydia/metabolismo , Infecções por Chlamydia/patologia , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Humanos , Imunidade Humoral , Imunização , Imunoglobulina G/imunologia , Camundongos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Infecções do Sistema Genital/imunologia , Doenças Bacterianas Sexualmente Transmissíveis/metabolismo , Doenças Bacterianas Sexualmente Transmissíveis/patologia
14.
PLoS One ; 13(12): e0208028, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30507951

RESUMO

BACKGROUND AND AIM: The majority of seasonal influenza vaccines are trivalent, containing two A virus strains (H1N1 and H3N2) and one B virus strain. The co-circulation of two distinct lineages of B viruses can lead to mismatch between the influenza B virus strain recommended for the trivalent seasonal vaccine and the circulating B virus. This has led some manufacturers to produce quadrivalent influenza vaccines containing one strain from each B lineage in addition to H1N1 and H3N2 strains. However, it is also important to know whether vaccines containing a single influenza B strain can provide cross-protectivity against viruses of the antigenically distinct lineage. The aim of this study was to assess in naïve ferrets the potential cross-protective activity of trivalent live attenuated influenza vaccine (T-LAIV) against challenge with a heterologous wild-type influenza B virus belonging to the genetically different lineage and to compare this activity with effectiveness of quadrivalent LAIV (Q-LAIV) in the ferret model. METHODS AND RESULTS: Ferrets were vaccinated with either one dose of trivalent LAIV containing B/Victoria or B/Yamagata lineage virus, or quadrivalent LAIV (containing both B lineages), or placebo. They were then challenged with B/Victoria or B/Yamagata lineage wild-type virus 28 days after vaccination. The ferrets were monitored for clinical signs and morbidity. Nasal swabs and lung tissue samples were analyzed for the presence of challenge virus. Antibody response to vaccination was assessed by routine hemagglutination inhibition assay. All LAIVs tested were found to be safe and effective against wild-type influenza B viruses based on clinical signs, and virological and histological data. The absence of interference between vaccine strains in trivalent and quadrivalent vaccine formulations was confirmed. Trivalent LAIVs were shown to have the potential to be cross-protective against infection with genetically different influenza B/Victoria and B/Yamagata lineages. CONCLUSIONS: In this ferret model, quadrivalent vaccine provided higher protection to challenge against both B/Victoria and B/Yamagata lineage viruses. However, T-LAIV provided some cross-protection in the case of a mismatch between circulating and vaccine type B strains. Notably, B/Victoria-based T-LAIV was more protective compared to B/Yamagata-based T-LAIV.


Assuntos
Proteção Cruzada/imunologia , Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Vacinação/métodos , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Proteção Cruzada/genética , Modelos Animais de Doenças , Feminino , Furões , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza B/genética , Vírus da Influenza B/imunologia , Vírus da Influenza B/patogenicidade , Vacinas contra Influenza/administração & dosagem , Influenza Humana/sangue , Influenza Humana/imunologia , Influenza Humana/virologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
15.
Expert Rev Vaccines ; 17(11): 967-976, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30365905

RESUMO

INTRODUCTION: The current seasonal influenza vaccine confers only limited protection due to waning antibodies or the antigenic shift and drift of major influenza surface antigens. A universal influenza vaccine which induces broad cross-protection against divergent influenza viruses with a comparable or better efficacy to seasonal influenza vaccines against matched strains will negate the need for an annual update of vaccine strains and protect against possible influenza pandemics. AREAS COVERED: In this review, we summarize the recent progress in nanoparticle-based universal influenza vaccine development. We compared the most potent nanoparticle categories, focusing on how they encapsulate conserved influenza epitopes, stimulate the innate and adaptive immune systems, exhibit antigen depot effect, extend the period for antigen-processing and presentation, and exert an intrinsic adjuvant effect on inducing robust immune responses. EXPERT COMMENTARY: The development of an effective universal influenza vaccine is an urgent task. Traditional influenza vaccine approaches are not sufficient for preventing recurrent epidemics or occasional pandemics. Nanoparticles are compatible with different immunogens and immune stimulators and can overcome the intrinsically low immunogenicity of conserved influenza virus antigens. We foresee that an affordable universal influenza vaccine will be available within ten years by integrating nanoparticles with other targeted delivery and controlled release technology.


Assuntos
Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Nanopartículas , Imunidade Adaptativa/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos Virais/imunologia , Proteção Cruzada/imunologia , Humanos , Imunidade Inata/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Influenza Humana/virologia
16.
Front Immunol ; 9: 2255, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30337924

RESUMO

Intranasally administered live-attenuated influenza virus (LAIV) vaccines provide significant protection against heterologous influenza A virus (IAV) challenge. However, LAIV administration can modify the bacterial microbiota in the upper respiratory tract, including alterations in species that cause pneumonia. We sought to evaluate the effect of Bordetella bronchiseptica colonization on LAIV immunogenicity and efficacy in swine, and the impact of LAIV and IAV challenge on B. bronchiseptica colonization and disease. LAIV immunogenicity was not significantly impacted by B. bronchiseptica colonization, but protective efficacy against heterologous IAV challenge in the upper respiratory tract was impaired. Titers of IAV in the nose and trachea of pigs that received LAIV were significantly reduced when compared to non-vaccinated, challenged controls, regardless of B. bronchiseptica infection. Pneumonia scores were higher in pigs colonized with B. bronchiseptica and challenged with IAV, but this was regardless of LAIV vaccination status. While LAIV vaccination provided significant protection against heterologous IAV challenge, the protection was not sterilizing and IAV replicated in the respiratory tract of all LAIV vaccinated pig. The interaction between IAV, B. bronchiseptica, and host led to development of acute-type B. bronchiseptica lesions in the lung. Thus, the data presented do not negate the efficacy of LAIV vaccination, but instead indicate that controlling B. bronchiseptica colonization in swine could limit the negative interaction between IAV and Bordetella on swine health.


Assuntos
Bordetella bronchiseptica/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Infecções por Orthomyxoviridae/imunologia , Administração Intranasal , Animais , Proteção Cruzada/imunologia , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/fisiologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Influenza Humana/virologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/virologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Suínos , Vacinação/métodos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
17.
J Virol ; 92(22)2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30185589

RESUMO

Influenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266-8280, 2016, https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses.IMPORTANCE Due to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.


Assuntos
Hemaglutininas Virais/genética , Hemaglutininas Virais/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia , Animais , Proteção Cruzada/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Sistema Respiratório/imunologia , Sistema Respiratório/virologia , Suínos , Replicação Viral/imunologia
18.
Future Microbiol ; 13: 1193-1208, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30117744

RESUMO

The current antituberculosis vaccine, BCG, was derived in the 1920s, yet the mechanisms of BCG-induced protective immunity and the variability of protective efficacy among populations are still not fully understood. BCG challenges the concept of vaccine specificity, as there is evidence that BCG may protect immunized infants from pathogens other than Mycobacterium tuberculosis - resulting in heterologous or nonspecific protection. This review summarizes the up-to-date evidence for this phenomenon, potential immunological mechanisms and implications for improved childhood vaccine design. BCG induces functional changes in infant innate and adaptive immune compartments, encouraging their collaboration in the first year of life. Understanding biological mechanisms beyond heterologous BCG effects is crucial to improve infant protection from infectious diseases.


Assuntos
Vacina BCG/imunologia , Imunidade Heteróloga/imunologia , Vacina BCG/administração & dosagem , Proteção Cruzada/imunologia , Humanos , Modelos Imunológicos , Mycobacterium tuberculosis/imunologia , Tuberculose/prevenção & controle , Vacinação/estatística & dados numéricos
19.
Am J Epidemiol ; 187(12): 2603-2614, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30084906

RESUMO

Despite all we have learned since 1918 about influenza virus and immunity, available influenza vaccines remain inadequate to control outbreaks of unexpected strains. Universal vaccines not requiring strain matching would be a major improvement. Their composition would be independent of predicting circulating viruses and thus potentially effective against unexpected drift or pandemic strains. This commentary explores progress with candidate universal vaccines based on various target antigens. Candidates include vaccines based on conserved viral proteins such as nucleoprotein and matrix, on the conserved hemagglutinin (HA) stem, and various combinations. Discussion covers the differing evidence for each candidate vaccine demonstrating protection in animals against influenza viruses of widely divergent HA subtypes and groups; durability of protection; routes of administration, including mucosal, providing local immunity; and reduction of transmission. Human trials of some candidate universal vaccines have been completed or are underway. Interestingly, the HA stem, like nucleoprotein and matrix, induces immunity that permits some virus replication and emergence of escape mutants fit enough to cause disease. Vaccination with multiple target antigens will thus have advantages over use of single antigens. Ultimately, a universal vaccine providing long-term protection against all influenza virus strains might contribute to pandemic control and routine vaccination.


Assuntos
Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Anticorpos Antivirais/imunologia , Proteção Cruzada/imunologia , Vias de Administração de Medicamentos , Epitopos de Linfócito T/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Vacinas contra Influenza/administração & dosagem , Neuraminidase/imunologia , Nucleoproteínas/imunologia , Proteínas da Matriz Viral/imunologia
20.
Front Immunol ; 9: 1705, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30105019

RESUMO

Skin vaccination using biodegradable microneedle patch (MNP) technology in vaccine delivery is a promising strategy showing significant advantages over conventional flu shots. In this study, we developed an MNP encapsulating a 4M2e-tFliC fusion protein and two types of whole inactivated influenza virus vaccines (H1N1 and H3N2) as a universal vaccine candidate. We demonstrated that mice receiving this tri-component influenza vaccine via MNP acquired improved IgG1 antibody responses with more balanced IgG1/IgG2a antibody responses and enhanced cellular immune responses, including increased populations of IL-4 and IFN-γ producing cells and higher frequencies of antigen-specific plasma cells compared with intramuscular injection. In addition, stronger germinal center reactions, increased numbers of Langerin-positive migratory dendritic cells, and increased cytokine secretion were observed in the skin-draining lymph nodes after immunization with the tri-component influenza MNP vaccine. The MNP-immunized group also possessed enhanced protection against a heterologous reassortant A/Shanghai/2013 H7N9 (rSH) influenza virus infection. Furthermore, the sera collected from 4M2e-tFliC MNP-immunized mice were demonstrated to have antiviral efficacy against reassortant A/Vietnam/1203/2004 H5N1 (rVet) and A/Shanghai/2013 H7N9 (rSH) virus challenges. The immunological advantages of skin vaccination with this tri-component MNP vaccine could offer a promising approach to develop an easily applicable and broadly protective universal influenza vaccine.


Assuntos
Proteção Cruzada/imunologia , Imunidade , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Administração Cutânea , Animais , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Humanos , Soros Imunes/imunologia , Imunidade Celular , Imunização , Injeções Intradérmicas , Células Madin Darby de Rim Canino , Camundongos , Agulhas , Vacinação/métodos
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