Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 796
Filtrar
1.
PLoS Negl Trop Dis ; 13(5): e0007417, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31150386

RESUMO

Oral cholera vaccines (OCVs) are being increasingly employed, but current killed formulations generally require multiple doses and lack efficacy in young children. We recently developed a new live-attenuated OCV candidate (HaitiV) derived from a Vibrio cholerae strain isolated during the 2010 Haiti cholera epidemic. HaitiV exhibited an unexpected probiotic-like activity in infant rabbits, preventing intestinal colonization and disease by wild-type V. cholerae before the onset of adaptive immunity. However, it remained unknown whether HaitiV would behave similarly to other OCVs to stimulate adaptive immunity against V. cholerae. Here, we orally immunized adult germ-free female mice to test HaitiV's immunogenicity. HaitiV safely and stably colonized vaccinated mice and induced known adaptive immune correlates of cholera protection within 14 days of administration. Pups born to immunized mice were protected against lethal challenges of both homologous and heterologous V. cholerae strains. Cross-fostering experiments revealed that protection was not dependent on vaccine colonization in or transmission to the pups. These findings demonstrate the protective immunogenicity of HaitiV and support its development as a new tool for limiting cholera.


Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/imunologia , Cólera/prevenção & controle , Probióticos/administração & dosagem , Vibrio cholerae/crescimento & desenvolvimento , Vibrio cholerae/imunologia , Imunidade Adaptativa , Administração Oral , Animais , Anticorpos Antibacterianos , Cólera/microbiologia , Vacinas contra Cólera/imunologia , Feminino , Humanos , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Coelhos , Vacinas Atenuadas/genética , Vacinas Atenuadas/imunologia , Vibrio cholerae/genética
2.
Org Biomol Chem ; 17(16): 4049-4060, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30950473

RESUMO

Glycoclusters displaying synthetic fragments of the O-specific polysaccharide (OSP) of Vibrio cholerae O1 serotype Inaba on a carbohydrate platform were prepared by Cu(i)-catalysed azide alkyne cycloaddition (CuAAC, click chemistry). The clusters were subsequently conjugated to BSA via squaric acid chemistry. Their immunoreactivity was compared with those of similar conventional conjugates, i.e. made from single oligosaccharides presented in non cluster form, using plasma of patients recovering from cholera. The results showed that the conjugates were displayed in immunologically relevant manners and that the immunoreactivity of hexasaccharide-cluster conjugates was similar to that of a conjugate displaying OSP isolated from wild type V. cholerae, further supporting the immunologic relevance of antigens made from synthetic oligosaccharides.


Assuntos
Cólera/imunologia , Antígenos O/imunologia , Vacinas/imunologia , Configuração de Carboidratos , Humanos , Antígenos O/química , Vibrio cholerae O1/química , Vibrio cholerae O1/imunologia
3.
PLoS One ; 14(3): e0213507, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845262

RESUMO

Serum vibriocidal antibody assays have long been used to evaluate the immunogenicity of cholera vaccines formulated with killed whole-cell Vibrio cholerae. However, the antibody isotypes responsible for the serum vibriocidal activity are not fully characterized. In this study, we examined 20 clinical serum samples obtained from human subjects who had been vaccinated with a killed, whole-cell cholera vaccine and a positive control, human convalescent sera with high vibriocidal activity, to determine which isotype antibody is associated with the vibriocidal activity. Antibody isotypes from pooled convalescent sera were fractionated by size-exclusion column chromatography, and the major vibriocidal activity was detected in the IgM fraction. Depletion of IgM antibodies in the convalescent sera produced a significant (P<0.05) decrease in vibriocidal activity (16-fold decrease), whereas only a small change was observed with depletion of IgG or IgA. In addition, anti-LPS IgM antibody showed the highest correlation with vibriocidal activity (Spearman correlation coefficient r = 0.846) among antibody isotypes against heat-killed V. cholerae, lipopolysaccharide (LPS), or major outer membrane protein (Omp U), while total IgG, IgA, or IgM antibody level was not correlated with vibriocidal activity in the 20 human clinical serum samples. Furthermore, human convalescent sera significantly (P<0.001) inhibited the attachment of V. cholerae to HT-29, a human intestinal epithelial cell in vitro. Interestingly, IgM-depleted convalescent sera could not effectively inhibit bacterial adherence compared with non-depleted sera (P<0.05). Finally, bacterial adhesion was significantly inhibited by sera with high vibriocidal titer compared with low-titer sera (P = 0.014). Collectively, we demonstrated that anti-V. cholerae LPS IgM is highly correlated with serum vibriocidal activity and it could be a surrogate antibody isotype representing protective antibodies against V. cholerae.


Assuntos
Anticorpos Antibacterianos/imunologia , Atividade Bactericida do Sangue/imunologia , Cólera/imunologia , Imunoglobulina M/imunologia , Lipopolissacarídeos/imunologia , Vibrio cholerae/imunologia , Cólera/patologia , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Feminino , Células HT29 , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino
4.
Avian Pathol ; 48(3): 221-229, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30640510

RESUMO

Pasteurella multocida (P. multocida), a causative agent of fowl cholera, is an important pathogen in the poultry industry. In the present study, we found that the inactivated vaccine of P. multocida grown in an iron-restricted medium provided better protection than that grown in normal medium. Thus, we adopted a comparative proteomics approach, by using two-dimensional gel electrophoresis (2-DE), coupled with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF MS), to profile the supernatant proteins associated with P. multocida under both conditions. Eleven upregulated proteins were identified, including aspartate ammonia-lyase (AspA), diacylglycerol kinase (DgK), 30S ribosomal protein S6 (RpsF), and eight outer membrane proteins (OMPs). To further characterize the three novel supernatant proteins identified under iron-restricted conditions, the AspA, DgK and RpsF proteins were expressed and purified, and used as immunogens to vaccinate chickens. The results showed that AspA, DgK and RpsF proteins induced 80.0%, 66.7%, and 80.0% immunity, respectively. These data indicate that the three novel proteins identified in the supernatant of the culture media might play important roles in the survival of bacteria under iron-restricted conditions, and thus protect chickens against P. multocida. These findings also suggest that the proteins identified can be used as subunit vaccines.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Galinhas/imunologia , Cólera/prevenção & controle , Pasteurella multocida/metabolismo , Doenças das Aves Domésticas/prevenção & controle , Animais , Aspartato Amônia-Liase/imunologia , Cólera/imunologia , Diacilglicerol Quinase/imunologia , Ferro/metabolismo , Pasteurella multocida/genética , Pasteurella multocida/imunologia , Doenças das Aves Domésticas/imunologia , Proteômica , Proteínas Ribossômicas/imunologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/veterinária , Vacinação/veterinária , Vacinas de Produtos Inativados/imunologia
5.
J Biol Dyn ; 13(1): 69-102, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30696390

RESUMO

In this paper, an age-structured cholera model with multiple transmissions, saturation incidence and imperfect vaccination is proposed. In the model, we consider both the infection age of infected individuals and the biological age of Vibrio cholerae in the aquatic environment. Asymptotic smoothness is verified as a necessary argument. By analysing the characteristic equations, the local stability of disease-free and endemic steady states is established. By using Lyapunov functionals and LaSalle's invariance principle, it is proved that the global dynamics of the model can be completely determined by basic reproduction number. The study of optimal control helps us seek cost-effective solutions of time-dependent vaccination strategy against cholera outbreaks. Numerical simulations are carried out to illustrate the corresponding theoretical results.


Assuntos
Cólera/epidemiologia , Cólera/transmissão , Modelos Biológicos , Vacinação , Fatores Etários , Cólera/imunologia , Simulação por Computador , Humanos , Incidência , Análise Numérica Assistida por Computador
6.
Vaccine ; 36(45): 6606-6614, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30314912

RESUMO

Cholera, a diarrheal disease primarily affecting vulnerable populations in developing countries, is estimated to cause disease in more than 2.5 million people and kill almost 100,000 annually. An oral cholera vaccine (OCV) has been available globally since 2001; the demand for this vaccine from affected countries has however been very low, due to various factors including vaccine price and mode of administration. The low demand for the vaccine and limited commercial incentives to invest in research and development of vaccines for developing country markets has kept the global supply of OCVs down. Since 1999, the International Vaccine Institute has been committed to make safe, effective and affordable OCVs accessible. Through a variety of partnerships with collaborators in Sweden, Vietnam, India and South Korea, and with public and private funding, IVI facilitated development and production of two affordable and WHO-prequalified OCVs and together with other stakeholders accelerated the introduction of these vaccines for the global public-sector market.


Assuntos
Vacinas contra Cólera/provisão & distribução , Cólera/imunologia , Cólera/prevenção & controle , Parcerias Público-Privadas , Administração Oral , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/uso terapêutico , Índia , República da Coreia , Suécia , Vietnã
7.
J Infect Dis ; 218(suppl_3): S165-S166, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30239901

RESUMO

The use of oral cholera vaccine (OCV) has increased since 2011, when Shanchol, the first OCV suitable for large-scale use, became available. Médecins Sans Frontières considers OCVs an essential cholera outbreak control tool and has contributed to generating new evidence on OCV use in outbreaks. We showed that large-scale mass campaigns are feasible during outbreaks, documented high short-term effectiveness and showed that vaccines are likely safe in pregnancy. We found that a single-dose regimen has high short-term effectiveness, making rapid delivery of vaccine during outbreaks easier, especially given the on-going global vaccine shortage. Despite progress, OCV has still not been used widely in some of the largest recent outbreaks and thousands of cholera deaths are reported every year. While working towards improving our tools to protect those most at-risk of cholera, we must strive to use all available effective interventions in efficient ways, including OCV, to prevent avoidable deaths today.


Assuntos
Vacinas contra Cólera/imunologia , Cólera/imunologia , Surtos de Doenças/prevenção & controle , Administração Oral , Humanos , Vacinação/métodos
9.
Iran J Immunol ; 15(3): 207-220, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30246696

RESUMO

BACKGROUND: Cholera disease caused by Vibrio cholerae remains a major cause of morbidity and mortality throughout the world. Various strategies with different proteins as immunogens have been tried for vaccine development, none of which have been sufficiently effective to preclude cholera. Chimeric proteins, with their ability to present multiple antigens at the same time, can play important roles in immunization. OBJECTIVE: To evaluate the immunogenicity of a chimeric construct, comprised of OmpW and CtxB as immunogenic proteins of Vibrio cholera, in BALB/c mice. METHODS: The construct was designed after bioinformatics assessments and then expressed in E.coli. Chimeric protein, OmpW, and CtxB were purified with Ni-NTA chromatography and confirmed by Western blotting. Mice were immunized with purified recombinant proteins. The antibody titers and specificity of the immune sera were then analyzed by ELISA and challenged on the pups of immunized mice with 1, 5 and 10 LD50. Mice ileal loop assay was also performed. RESULTS: Significant differences were observed in antibody titers in immunized mice compared to the control groups. Infant mouse challenge was performed so as to compare the protective efficacies of the selected immunogen regimens. Of the Pups from dams immunized with chimeric protein which received 1 LD50, 75% survived. Pups belonging to PBS-immunized dams, experienced 100% mortality. The serum raised toward immunogenic construct, inhibited cholera toxin activity in ileal loop test up to 68%. CONCLUSION: Chimeric construct is able to induce the immune system and provide up to 75% inhibition of toxin activity against 1 LD50 of Vibrio cholerae.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Toxina da Cólera/genética , Vacinas contra Cólera/imunologia , Cólera/imunologia , Proteínas Recombinantes de Fusão/genética , Vibrio cholerae/genética , Animais , Anticorpos Antibacterianos/sangue , Biologia Computacional , Escherichia coli/genética , Feminino , Engenharia Genética , Humanos , Imunidade Humoral , Imunização , Camundongos , Camundongos Endogâmicos BALB C
10.
J Infect Dis ; 218(suppl_3): S141-S146, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30184117

RESUMO

Vibrio cholerae is a prototypical noninvasive mucosal pathogen, yet infection generates long-lasting protection against subsequent disease. Vibriocidal antibody responses are an imperfect but established correlate of protection against cholera following both infection and vaccination. However, vibriocidal antibody responses are likely a surrogate marker for longer-lasting functional immune responses that target the O-polysaccharide antigen at the mucosal surface. While the current bivalent inactivated oral whole cell vaccine is being increasingly used to prevent cholera in areas where the disease is a threat, the most significant limitation of this vaccine is it offers relatively limited direct protection in young children. Future strategies for cholera vaccination include the development of cholera conjugate vaccines and the further development of live attenuated vaccines. Ultimately, the goal of a multivalent vaccine for cholera and other childhood enteric infections that can be incorporated into a standard immunization schedule should be realized.


Assuntos
Vacinas contra Cólera/imunologia , Cólera/imunologia , Imunidade/imunologia , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos/imunologia , Toxina da Cólera/imunologia , Humanos , Esquemas de Imunização , Antígenos O/imunologia , Vacinação/métodos , Vacinas Atenuadas/imunologia , Vacinas Conjugadas/imunologia , Vacinas de Produtos Inativados/imunologia , Vibrio cholerae/imunologia
12.
Expert Opin Biol Ther ; 18(9): 983-988, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30107757

RESUMO

INTRODUCTION: Cholera remains a public health threat. The development of safe, effective, easy-to-administer, heat-stable, and cheap killed whole cell oral cholera vaccines (OCVs) has provided an additional tool to counter cholera. In this meta-opinion, we review the challenges of delivering OCVs through the existing public health infrastructure in vulnerable areas. AREAS COVERED: We provide an overview of the available vaccines against cholera, the existing evidence about the effectiveness of a two-dose as well as a single-dose OCV strategy. We also highlight the experience from the public health campaigns for OCV deployment. EXPERT OPINION: Several public health experiences have shown the feasibility of incorporating OCVs into the public health response against cholera. Combined with a comprehensive water, sanitation, and hygiene (WaSH) improvement plan, OCVs need to be deployed in identified vulnerable areas, targeting the highest risk groups first. Vaccination programs should not be deployed in lieu of investments in WaSH services, but as a complimentary service in a comprehensive, cholera control intervention package. It has been a challenge to have high two-dose coverage across all eligible recipients, necessitating the adoption of innovative strategies to boost coverage. Longer intervals between doses may help to overcome resource and logistical limitations enabling higher coverage.


Assuntos
Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Implementação de Plano de Saúde , Programas de Imunização , Vacinas de Produtos Inativados/administração & dosagem , Administração Oral , Conscientização , Cólera/imunologia , Conhecimentos, Atitudes e Prática em Saúde , Implementação de Plano de Saúde/métodos , Implementação de Plano de Saúde/organização & administração , Implementação de Plano de Saúde/normas , Humanos , Programas de Imunização/organização & administração , Programas de Imunização/normas , Controle de Infecções/métodos , Controle de Infecções/organização & administração , Controle de Infecções/normas , Cobertura Vacinal/organização & administração , Cobertura Vacinal/normas
13.
Vet Microbiol ; 222: 114-123, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30080666

RESUMO

Pasteurella multocida is the causative agent of avian cholera, an important economic and ecological disease that can present as a peracute, acute, chronic, or asymptomatic infection. Acute avian cholera is associated with encapsulated P. multocida, while chronic and asymptomatic cases of avian cholera may be associated with capsule-deficient P. multocida isolates. We hypothesize that biofilm formation is also associated with chronic and asymptomatic avian cholera. Experimental infections of chickens with encapsulated, biofilm-deficient P. multocida strain X73, proficient biofilm forming P. multocida strain X73ΔhyaD, and proficient biofilm forming clinical strains 775 and 756 showed that virulence was inversely correlated with biofilm formation. Biofilm-proficient isolates induced chronic avian cholera in the chicken host. Histopathological analysis was used to show that biofilm-proficient isolates induced little inflammation in the lungs, heart, and liver, while biofilm-deficient isolates induced greater inflammation and induced the recruitment of heterophil granulocytes. Putative biofilm matrix material and exopolysaccharide was detected in pulmonary tissue of chickens diagnosed with chronic avian cholera using scanning electron microscopy and a fluorescently-tagged lectin, respectively, supporting a role for biofilm in chronic avian cholera. P. multocida induced Th1 and Th17 immune responses during acute and chronic avian cholera, as determined by quantitative real-time PCR of splenic cytokine genes. Chickens that succumbed to acute avian cholera after experimental challenge with strain X73 had high levels of INF-γ, IL-1ß, IL-6, IL-12A, IL-22, IL-17A, and IL-17RA expressed in the spleen compared to all other experimental groups. Birds infected with capsule-deficient strains had chronic infections lasting 7 days or longer, and had increased levels of IL-17RA, CCR6, and IL-16 compared to non-infected control chickens. However, specific antibody titers increased only transiently to capsule-deficient strains and were low, indicating that antibodies are less important in managing and clearing P. multocida infections.


Assuntos
Biofilmes/crescimento & desenvolvimento , Galinhas/imunologia , Cólera/veterinária , Infecções por Pasteurella/veterinária , Pasteurella multocida/imunologia , Pasteurella multocida/patogenicidade , Doença Aguda , Animais , Quimiocinas/imunologia , Cólera/imunologia , Cólera/microbiologia , Cólera/mortalidade , Doença Crônica , Citocinas/imunologia , Infecções por Pasteurella/imunologia , Infecções por Pasteurella/microbiologia , Infecções por Pasteurella/mortalidade , Pasteurella multocida/isolamento & purificação , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/mortalidade , Células Th1/imunologia , Células Th17/imunologia , Virulência
14.
Microb Pathog ; 124: 170-177, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30138759

RESUMO

Vibrio cholera is a Gram-negative pathogen that causes diarrheal disease. The B subunit of Chlora toxin (CtxB) is one of the most important antigens of Vibrio cholera in which mediates the attachment of the bacteria to target cells. The aim of this study was to prepare chitosan nanoparticles containing CtxB and evaluate the effect of the antigen entrapment on the immunogenicity of this antigen. For this, the pET28a vector was induced using IPTG. Recombinant CtxB protein was expressed and purified using Ni-NTA column and finally was confirmed by western blotting. Following the confirmation of the protein entrapment onto the chitosan nanoparticles, the formulation was prescribed to BALB/c mice in three groups, including oral, oral-injection and injection groups. Serum and fecal IgA and IgG were evaluated by ELISA test. Finally, challenge of immunized mice was performed using Ctx toxin and rabbit ileal loop test. Using SDS-PAGE and western blotting, the 17.5 kDa recombinant CtxB was confirmed. Size electrical charge and of nanoparticles were determined and approved by Zetasizer. Nanoparticles prescription showed 1/102400 IgG endpoint titers for injection groups and 1/1600, 1/6400 for oral, oral-injection groups respectively and Serum and fecal IgA endpoint titers showed above 1/160 in all groups. Furthermore, immunized mice were able to neutralize Ctx toxin by ileal loop test. The CtxB is a suitable immunogen of V. cholera to be incorporated in both protective and preventive vaccines. Chitosan nanoparticles improve the immune responses and it may be used as a carrier for vaccine delivery.


Assuntos
Antígenos de Bactérias/imunologia , Toxina da Cólera/imunologia , Cólera/prevenção & controle , Nanopartículas/química , Vibrio cholerae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/genética , Quitosana/administração & dosagem , Quitosana/química , Cólera/imunologia , Cólera/microbiologia , Toxina da Cólera/administração & dosagem , Toxina da Cólera/química , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Coelhos , Vibrio cholerae/química , Vibrio cholerae/genética
15.
Curr Opin Infect Dis ; 31(5): 455-461, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30048254

RESUMO

PURPOSE OF REVIEW: In this review, we will examine updates in cholera epidemiology, advances in our understanding of pathogenesis and protective immunity, and changes to prevention strategies. RECENT FINDINGS: New modeling techniques and molecular epidemiology have led to advancements in our understanding of how Vibrio cholerae has persisted and re-emerged in new areas during the seventh pandemic. Use of next-generation sequencing has shed new light on immune responses to disease and vaccination, and the role of the gut microbiome in cholera. Increased efficacy and availability of vaccines have made long-term goals of global control of cholera more achievable. SUMMARY: Advancements in our understanding of immunity and susceptibility to V. cholerae, in addition to an increased global commitment to disease prevention, have led to optimism for the future of cholera prevention.


Assuntos
Vacinas contra Cólera/imunologia , Cólera/epidemiologia , Cólera/prevenção & controle , Controle de Doenças Transmissíveis/métodos , Transmissão de Doença Infecciosa/prevenção & controle , Pandemias , Vibrio cholerae/imunologia , Antibiose , Pesquisa Biomédica/tendências , Cólera/imunologia , Cólera/fisiopatologia , Vacinas contra Cólera/administração & dosagem , Microbioma Gastrointestinal , Saúde Global , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Humanos , Epidemiologia Molecular/métodos , Vibrio cholerae/classificação , Vibrio cholerae/genética
16.
Hum Vaccin Immunother ; 14(9): 2323-2328, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29852089

RESUMO

The aim of this study was to assess the cumulative immunogenicity properties of rZot and rAce combination and their potential ability to increase the clearance rate of pathogenic standard Vibrio cholerae strain in challenge experiments in mice model. The recombinant Zot and Ace proteins were produced and used to raise polyclonal antibodies of anti-Zot and anti-Ace recombinant proteins in rabbit. Six-week female BALB/c mice were immunized with different antigens via oral route. Blood samples were collected, and the total amount of IgG and IgA antibodies against rZot and rAce were measured in blood and stool samples of each immunized mouse. Challenge experiments were done with toxigenic V. cholerae strain. The anti-Zot and anti-Ace IgG titers were significantly higher in immunized mice in comparison with control group. The IgG and IgA titers were higher in the sera of mice immunized by recombinant Ace than in group immunized by rZot, indicating the higher immunogenicity of rAce than rZot. The use of rAce and rZot mixture led to synergistic activities in increasing the level of IgG and IgA in comparison with the use of each protein separately. The clearance rate was significantly higher in different challenge groups than in the control group, and the coherence between rZot and rAce reduced the bacterial shedding significantly. In conclusion, the use of recombinant Zot and Ace mixture can produce the proper amount of IgA and IgG against to toxigenic V. cholerae, reduce bacterial shedding in immunized mice significantly, and be used as a potent candidate in cholera vaccine research.


Assuntos
Antígenos de Bactérias/imunologia , Vacinas contra Cólera/imunologia , Cólera/imunologia , Cólera/prevenção & controle , Vibrio cholerae/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/genética , Modelos Animais de Doenças , Fezes/química , Feminino , Imunoglobulina A/análise , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Vibrio cholerae/genética
17.
Sci Transl Med ; 10(445)2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29899024

RESUMO

Outbreaks of cholera, a rapidly fatal diarrheal disease, often spread explosively. The efficacy of reactive vaccination campaigns-deploying Vibrio cholerae vaccines during epidemics-is partially limited by the time required for vaccine recipients to develop adaptive immunity. We created HaitiV, a live attenuated cholera vaccine candidate, by deleting diarrheagenic factors from a recent clinical isolate of V. cholerae and incorporating safeguards against vaccine reversion. We demonstrate that administration of HaitiV 24 hours before lethal challenge with wild-type V. cholerae reduced intestinal colonization by the wild-type strain, slowed disease progression, and reduced mortality in an infant rabbit model of cholera. HaitiV-mediated protection required viable vaccine, and rapid protection kinetics are not consistent with development of adaptive immunity. These features suggest that HaitiV mediates probiotic-like protection from cholera, a mechanism that is not known to be elicited by traditional vaccines. Mathematical modeling indicates that an intervention that works at the speed of HaitiV-mediated protection could improve the public health impact of reactive vaccination.


Assuntos
Cólera/prevenção & controle , Vacinas Atenuadas/uso terapêutico , Imunidade Adaptativa/fisiologia , Animais , Cólera/imunologia , Progressão da Doença , Cinética , Modelos Teóricos , Coelhos
18.
PLoS Negl Trop Dis ; 12(4): e0006399, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29684006

RESUMO

BACKGROUND: The mediators of protection against cholera, a severe dehydrating illness of humans caused by Vibrio cholerae, are unknown. We have previously shown that plasma IgA as well as memory B IgG cells targeting lipopolysaccharide (LPS) of Vibrio cholerae O1 correlate with protection against V. cholerae O1 infection among household contacts of cholera patients. Protection against cholera is serogroup specific, and serogroup specificity is defined by the O-specific polysaccharide (OSP) component of LPS. Therefore, we prospectively followed household contacts of cholera patients to determine whether OSP-specific immune responses present at the time of enrollment are associated with protection against V. cholerae infection. METHODOLOGY: In this study, we enrolled two hundred forty two household contacts of one hundred fifty index patients who were infected with Vibrio cholerae. We determined OSP-specific memory B cells and plasma IgA, IgG and IgM antibody responses on study entry (day 2). PRINCIPLE FINDINGS: The presence of OSP-specific plasma IgA, IgM, and IgG antibody responses on study entry were associated with a decrease in the risk of infection in household contacts (IgA, p = 0.015; IgM, p = 0.01, and IgG, p = 0.024). In addition, the presence of OSP-specific IgG memory B cell responses in peripheral blood on study entry was also associated with a decreased risk of infection (44% reduction; 95% CI: 31.1 to 99.8) in contacts. No protection was associated with cholera toxin B subunit (CtxB)-specific memory B cell responses. CONCLUSION: These results suggest that immune responses that target OSP, both in plasma and memory responses, may be important in mediating protection against infection with V. cholerae O1.


Assuntos
Linfócitos B/imunologia , Cólera/prevenção & controle , Memória Imunológica , Antígenos O/imunologia , Plasma/imunologia , Vibrio cholerae O1/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Bangladesh , Criança , Pré-Escolar , Cólera/imunologia , Cólera/microbiologia , Características da Família , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Vibrio cholerae O1/genética , Adulto Jovem
19.
PLoS Negl Trop Dis ; 12(4): e0006376, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29624592

RESUMO

BACKGROUND: Cholera is an acute voluminous dehydrating diarrheal disease caused by toxigenic strains of Vibrio cholerae O1 and occasionally O139. A growing body of evidence indicates that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae are involved in mediating protection against cholera. We therefore assessed whether antibody responses against OSP occur after vaccination with live attenuated oral cholera vaccine CVD 103-HgR, and whether such responses correlate with protection against cholera. METHODOLOGY: We assessed adult North American volunteers (n = 46) who were vaccinated with 5 × 108 colony-forming units (CFU) of oral cholera vaccine CVD 103-HgR and then orally challenged with approximately 1 × 105 CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961, either 10 or 90 days post-vaccination. PRINCIPAL FINDINGS: Vaccination was associated with induction of significant serum IgM and IgA anti-OSP and vibriocidal antibody responses within 10 days of vaccination. There was significant correlation between anti-OSP and vibriocidal antibody responses. IgM and IgA anti-OSP responses on day 10 following vaccination were associated with lower post-challenge stool volume (r = -0.44, P = 0.002; r = -0.36, P = 0.01; respectively), and none of 27 vaccinees who developed a ≥1.5 fold increase in any antibody isotype targeting OSP on day 10 following vaccination compared to baseline developed moderate or severe cholera following experimental challenge, while 5 of 19 who did not develop such anti-OSP responses did (P = 0.01). CONCLUSION: Oral vaccination with live attenuated cholera vaccine CVD 103-HgR induces antibodies that target V. cholerae OSP, and these anti-OSP responses correlate with protection against diarrhea following experimental challenge with V. cholerae O1. TRIAL REGISTRATION: ClinicalTrials.gov NCT01895855.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Antígenos O/imunologia , Administração Oral , Adulto , Formação de Anticorpos , Cólera/imunologia , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Estados Unidos , Vacinação/métodos , Vibrio cholerae O1/imunologia , Voluntários
20.
J Infect Dis ; 218(4): 645-653, 2018 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-29659916

RESUMO

Background: Cholera is a public health problem worldwide, and the risk factors for infection are only partially understood. Methods: We prospectively studied household contacts of patients with cholera to compare those who were infected to those who were not. We constructed predictive machine learning models of susceptibility, using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. Results: We found that machine learning models based on gut microbiota, as well as models based on known clinical and epidemiological risk factors, predicted V. cholerae infection. A predictive gut microbiota of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. Conclusion: These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.


Assuntos
Cólera/epidemiologia , Cólera/imunologia , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Microbiota , Vibrio cholerae/crescimento & desenvolvimento , Vibrio cholerae/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Simulação por Computador , Métodos Epidemiológicos , Características da Família , Saúde da Família , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA