scholarly journals Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice

2012 ◽  
Vol 19 (4) ◽  
pp. 594-602 ◽  
Author(s):  
A. A. Tarique ◽  
A. Kalsy ◽  
M. Arifuzzaman ◽  
S. M. Rollins ◽  
R. C. Charles ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vibrio Cholerae ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Immune Serum ◽  
Whole Cell ◽  
Content Type ◽  
Specific Polysaccharide ◽  
Subcutaneous Immunization ◽  
Cholera Vaccination

ABSTRACTA shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide ofVibrio choleraeO1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) orEscherichia coliheat-labile toxin (LT) following oral priming with attenuatedV. choleraeO1 vaccine strain O395-NT resulted in significant increases in serum anti-V. choleraeLPS IgG, IgM, and IgA (P< 0.01) responses as well as in anti-Ogawa (P< 0.01) and anti-Inaba (P< 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P< 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses againstV. cholerae.

scholarly journals Posttranslational Regulation of IL-23 Production Distinguishes the Innate Immune Responses to Live Toxigenic versus Heat-Inactivated Vibrio cholerae

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Ana A. Weil ◽  
Crystal N. Ellis ◽  
Meti D. Debela ◽  
Taufiqur R. Bhuiyan ◽  
Rasheduzzaman Rashu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Protective Immunity ◽  
Innate Immune ◽  
Posttranslational Regulation ◽  
Content Type ◽  
In Cells ◽  
Cholera Vaccines

ABSTRACT Vibrio cholerae infection provides long-lasting protective immunity, while oral, inactivated cholera vaccines (OCV) result in more-limited protection. To identify characteristics of the innate immune response that may distinguish natural V. cholerae infection from OCV, we stimulated differentiated, macrophage-like THP-1 cells with live versus heat-inactivated V. cholerae with and without endogenous or exogenous cholera holotoxin (CT). Interleukin 23A gene (IL23A) expression was higher in cells exposed to live V. cholerae than in cells exposed to inactivated organisms (mean change, 38-fold; 95% confidence interval [95% CI], 4.0 to 42; P < 0.01). IL-23 secretion was also higher in cells exposed to live V. cholerae than in cells exposed to inactivated V. cholerae (mean change, 5.6-fold; 95% CI, 4.4 to 11; P < 0.001). This increase in IL-23 secretion was more marked than for other key innate immune cytokines (e.g., IL-1β and IL-6) and dependent on exposure to the combination of both live V. cholerae and CT. While IL-23 secretion was reduced following stimulation with either heat-inactivated wild-type V. cholerae or a live isogenic ctxAB mutant of V. cholerae, the addition of exogenous CT restored IL-23 secretion in combination with the live isogenic ctxAB mutant V. cholerae, but not when it was paired with stimulation by heat-inactivated V. cholerae. The posttranslational regulation of IL-23 under these conditions was dependent on the activity of the cysteine protease cathepsin B. In humans, IL-23 promotes the differentiation of Th17 cells to T follicular helper cells, which maintain and support long-term memory B cell generation after infection. Based on these findings, the stimulation of IL-23 production may be a determinant of protective immunity following V. cholerae infection. IMPORTANCE An episode of cholera provides better protection against reinfection than oral cholera vaccines, and the reasons for this are still under study. To better understand this, we compared the immune responses of human cells exposed to live Vibrio cholerae with those of cells exposed to heat-killed V. cholerae (similar to the contents of oral cholera vaccines). We also compared the effects of active cholera toxin and the inactive cholera toxin B subunit (which is included in some cholera vaccines). One key immune signaling molecule, IL-23, was uniquely produced in response to the combination of live bacteria and active cholera holotoxin. Stimulation with V. cholerae that did not produce the active toxin or was killed did not produce an IL-23 response. The stimulation of IL-23 production by cholera toxin-producing V. cholerae may be important in conferring long-term immunity after cholera.

scholarly journals Memory B Cell and Other Immune Responses in Children Receiving Two Doses of an Oral Killed Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

2012 ◽  
Vol 19 (5) ◽  
pp. 690-698 ◽  
Author(s):  
Daniel T. Leung ◽  
Mohammad Arif Rahman ◽  
M. Mohasin ◽  
Sweta M. Patel ◽  
Amena Aktar ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
B Cell ◽  
Protective Efficacy ◽  
Cholera Toxin B Subunit ◽  
Cholera Vaccine ◽  
Wild Type ◽  
Memory B Cell ◽  
Content Type ◽  
Cholera Vaccination

ABSTRACTCurrent oral cholera vaccines induce lower protective efficacy and shorter duration of protection against cholera than wild-type infection provides, and this difference is most pronounced in young children. Despite this, there are limited data comparing immune responses in children following wild-type disease versus vaccination, especially with regard to memory responses associated with long-term immunity. Here, we report a comparison of immune responses in young children (2 to 5 years of age;n= 20) and older children (6 to 17 years of age;n= 20) given two doses of an oral killed cholera vaccine containing recombinant cholera toxin B subunit (CtxB) 14 days apart and compare these responses to those induced in similarly aged children recovering from infection withVibrio choleraeO1 Ogawa in Bangladesh. We found that the two vaccine groups had comparable vibriocidal and lipopolysaccharide (LPS)-specific plasma antibody responses. Vaccinees developed lower levels of IgG memory B cell (MBC) responses against CtxB but no significant MBC responses against LPS. In contrast, children recovering from natural cholera infection developed prominent LPS IgG and IgA MBC responses, as well as CtxB IgG MBC responses. Plasma LPS IgG, IgA, and IgM responses, as well as vibriocidal responses, were also significantly higher in children following disease than after vaccination. Our findings suggest that acute and memory immune responses following oral cholera vaccination in children are significantly lower than those observed following wild-type disease, especially responses targeting LPS. These findings may explain, in part, the lower efficacy of oral cholera vaccination in children.

scholarly journals Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

2013 ◽  
Vol 20 (6) ◽  
pp. 780-788 ◽  
Author(s):  
Daniel T. Leung ◽  
Taher Uddin ◽  
Peng Xu ◽  
Amena Aktar ◽  
Russell A. Johnson ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Cholera Vaccine ◽  
Wild Type ◽  
Older Children ◽  
Content Type ◽  
Oral Cholera Vaccine ◽  
Specific Polysaccharide

ABSTRACTCurrent oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses toVibrio choleraelipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses againstV. choleraeO-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months,n= 15), young children (24 to 59 months,n= 14), and older children (5 to 15 years,n= 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response toV. choleraeOSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-typeV. choleraeO1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group.

scholarly journals Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera

2012 ◽  
Vol 19 (11) ◽  
pp. 1712-1721 ◽  
Author(s):  
Russell A. Johnson ◽  
Taher Uddin ◽  
Amena Aktar ◽  
M. Mohasin ◽  
Mohammad Murshid Alam ◽  
...  
Keyword(s):  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Vibrio Cholerae ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Content Type ◽  
Specific Polysaccharide ◽  
Vibrio Cholerae O1 ◽  
Human Immune ◽  
El Tor

ABSTRACTImmunity againstVibrio choleraeO1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses toV. choleraeOSP have not previously been characterized. We assessed immune responses againstV. choleraeOSP in adults with cholera caused byV. choleraeO1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core–bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R= 0.86, 0.73, and 0.91, respectively;P< 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R= 0.60, 0.60, and 0.92, respectively;P< 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R= 0.80 and 0.66, respectively;P< 0.001). Addition of either OSPc:BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targetingV. choleraeLPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targetingV. choleraeOSP.

scholarly journals Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

2013 ◽  
Vol 81 (12) ◽  
pp. 4626-4634 ◽  
Author(s):  
Ediane B. Silva ◽  
Andrew Goodyear ◽  
Marjorie D. Sutherland ◽  
Nicole L. Podnecky ◽  
Mercedes Gonzalez-Juarrero ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Protective Immunity ◽  
Burkholderia Pseudomallei ◽  
Partial Protection ◽  
Content Type ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Immune Correlates ◽  
Draining Lymph Nodes

ABSTRACTInfections with the Gram-negative bacteriumBurkholderia pseudomallei(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections withB. pseudomallei. At present, our understanding of what constitutes effective protective immunity againstB. pseudomalleiinfection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acuteB. pseudomalleiinfection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excludedpurMdeletion mutant ofB. pseudomallei(strain Bp82) and then subjected to intranasal challenge with virulentB. pseudomalleistrain 1026b. Immunization with Bp82 generated significant protection from challenge withB. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuatedBurkholderiavaccine strain was dependent primarily on generation of effective humoral immune responses.

scholarly journals Protective Efficacy of an Inactive Vaccine Based on the LY02 Isolate against AcuteHaemophilus parasuisInfection in Piglets

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Hua Li ◽  
Guo-Zhen Zhao ◽  
Long-Xin Qiu ◽  
Ai-Ling Dai ◽  
Wang-Wei Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Haemophilus Parasuis ◽  
Fujian Province ◽  
Cellular Immune Responses ◽  
Glässer’S Disease ◽  
Potential Vaccine ◽  
Cellular Immune ◽  
Glasser's Disease

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.

scholarly journals A Self-Assembling Whole-Cell Vaccine Antigen Presentation Platform

2018 ◽  
Vol 200 (15) ◽  
Author(s):  
Julie Liao ◽  
Daniel R. Smith ◽  
Jóhanna Brynjarsdóttir ◽  
Paula I. Watnick
Keyword(s):  
Vibrio Cholerae ◽  
Bacterial Biofilm ◽  
Cell Vaccine ◽  
Secreted Protein ◽  
Proof Of Concept ◽  
Whole Cell ◽  
Content Type ◽  
Self Assembling ◽  
Whole Cell Vaccine ◽  
Common Infection

ABSTRACTDiarrhea is the most common infection in children under the age of 5 years worldwide. In spite of this, only a few vaccines to treat infectious diarrhea exist, and many of the available vaccines are sparingly and sporadically administered. Major obstacles to the development and widespread implementation of vaccination include the ease and cost of production, distribution, and delivery. Here we present a novel, customizable, and self-assembling vaccine platform that exploits theVibrio choleraebacterial biofilm matrix for antigen presentation. We use this technology to create a proof-of-concept, live-attenuated whole-cell vaccine that is boosted by spontaneous association of a secreted protein antigen with the cell surface. Sublingual administration of this live-attenuated vaccine to mice confers protection againstV. choleraechallenge and elicits the production of antigen-specific IgA in stool. The platform presented here enables the development of antigen-boosted vaccines that are simple to produce and deliver, addressing many of the obstacles to vaccination against diarrheal diseases. This may also serve as a paradigm for the development of broadly protective biofilm-based vaccines against other mucosal infections.IMPORTANCEDiarrheal disease is the most common infection afflicting children worldwide. In resource-poor settings, these infections are correlated with cognitive delay, stunted growth, and premature death. With the development of efficacious, affordable, and easily administered vaccines, such infections could be prevented. While a major focus of research on biofilms has been their elimination, here we harness the bacterial biofilm to create a customizable platform for cost-effective, whole-cell mucosal vaccines that self-incorporate secreted protein antigens. We use this platform to develop a sublingually administered live-attenuated prototype vaccine based onVibrio cholerae. This serves not only as a proof of concept for a multivalent vaccine against common bacterial enteric pathogens but also as a paradigm for vaccines utilizing other bacterial biofilms to target mucosal infections.

scholarly journals Vaccination with Secreted Aspartyl Proteinase 2 Protein from Candida parapsilosis Can Enhance Survival of Mice during C. tropicalis-Mediated Systemic Candidiasis

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Manisha Shukla ◽  
Soma Rohatgi
Keyword(s):  
B Cells ◽  
Plasma Cells ◽  
Protective Efficacy ◽  
Immune Serum ◽  
Systemic Candidiasis ◽  
Biofilm Inhibition ◽  
Content Type ◽  
Humoral And Cellular Immunity ◽  
Secreted Aspartyl Proteinase

ABSTRACT The rising incidence of non-albicans Candida species globally, along with the emergence of drug resistance, is a cause for concern. This study investigated the protective efficacy of secreted aspartyl proteinase 2 (Sap2) in systemic C. tropicalis infection. Vaccination with recombinant Sap2 (rSap2) protein from C. parapsilosis enhanced survival of mice compared to rSap2 vaccinations from C. albicans (P = 0.02), C. tropicalis (P = 0.06), and sham immunization (P = 0.04). Compared to sham-immunized mice, the fungal CFU number was significantly reduced in organs of Sap2-parapsilosis-immunized mice. Histopathologically, increased neutrophilic recruitment was observed in Sap2-parapsilosis- and Sap2-tropicalis-immunized mice. Among different rSap2 proteins, Sap2-parapsilosis vaccination induced increased titers of Sap2-specific Ig, IgG, and IgM antibodies, which could bind whole fungus. Between different groups, sera from Sap2-parapsilosis-vaccinated mice exhibited increased C. tropicalis biofilm inhibition ability in vitro and enhanced neutrophil-mediated fungal killing. Passive transfer of anti-Sap2-parapsilosis immune serum in naive mice significantly reduced fungal burdens compared to those in mice receiving anti-sham immune serum. Higher numbers of plasma cells and Candida-binding B cells in Sap2-vaccinated mice suggest a role of B cells during early stages of Sap2-mediated immune response. Additionally, increased levels of Th1/Th2/Th17 cytokines observed in Sap2-parapsilosis-vaccinated mice indicate immunomodulatory properties of Sap2. Epitope analysis performed using identified B-cell epitopes provides a basis to understand differences in immunogenicity observed among Sap2-antigens and can aid the development of a multivalent or multiepitope anti-Candida vaccine(s). In summary, our results suggest that Sap2-parapsilosis vaccination can improve mouse survival during C. tropicalis infection by inducing both humoral and cellular immunity, and higher titers of Sap2-induced antibodies are beneficial during systemic candidiasis.

scholarly journals Enumeration of Gut-Homing β7-Positive, Pathogen-Specific Antibody-Secreting Cells in Whole Blood from Enterotoxigenic Escherichia coli- and Vibrio cholerae-Infected Patients, Determined Using an Enzyme-Linked Immunosorbent Spot Assay Technique

2015 ◽  
Vol 23 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Taufiqur Rahman Bhuiyan ◽  
Mohammad Rubel Hoq ◽  
Naoshin Sharmin Nishat ◽  
Deena Al Mahbuba ◽  
Rasheduzzaman Rashu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Vibrio Cholerae ◽  
Elispot Assay ◽  
Enterotoxigenic Escherichia Coli ◽  
Watery Diarrhea ◽  
Content Type ◽  
A Cell ◽  
Mucosal Immune Responses ◽  
Antibody Secreting Cells

ABSTRACTVibrio choleraeand enterotoxigenicEscherichia coli(ETEC) are noninvasive mucosal pathogens that cause acute watery diarrhea in people in developing countries. Direct assessment of the mucosal immune responses to these pathogens is problematic. Surrogate markers of local mucosal responses in blood are increasingly being studied to determine the mucosal immune responses after infection. However, the volume of blood available in children and infants has limited this approach. We assessed whether an approach that first isolates β7-positive cells from a small volume of blood would allow measurement of the antigen-specific immune responses in patients with cholera and ETEC infection. β7 is a cell surface marker associated with mucosal homing. We isolated β7-expressing cells from blood on days 2, 7, and 30 and used an enzyme-linked immunosorbent spot (ELISPOT) assay to assess the gut-homing antibody-secreting cells (ASCs) specific to pathogen antigens. Patients with ETEC diarrhea showed a significant increase in toxin-specific gut-homing ASCs at day 7 compared to the levels at days 2 and 30 after onset of illness and to the levels in healthy controls. Similar elevations of responses to the ETEC colonization factors (CFs) CS6 and CFA/I were observed in patients infected with CS6- and CFA/I-positive ETEC strains. Antigen-specific gut-homing ASCs to the B subunit of cholera toxin and cholera-specific lipopolysaccharides (LPS) were also observed on day 7 after the onset of cholera using this approach. This study demonstrates that a simple ELISPOT assay can be used to study the mucosal immunity to specific antigens using a cell-sorting protocol to isolate mucosal homing cells, facilitating measurement of mucosal responses in children following infection or vaccination.

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