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Ann-mari Svennerholm - One of the best experts on this subject based on the ideXlab platform.
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assessing antigen specific hla dr Antibody Secreting Cell dr asc responses in whole blood in enteric infections using an elispot technique
Microbes and Infection, 2017Co-Authors: Taufiqur Rahman Bhuiyan, Edward T Ryan, Stephen B Calderwood, Rasheduzzaman Rashu, Kamrul Islam, Naoshin Sharmin Nishat, Deena Al Mahbuba, Lazina Hossain, Jason B Harris, Ann-mari SvennerholmAbstract:Abstract Antibody Secreting Cells (ASCs) generate antibodies in an antigen-specific manner as part of the adaptive immune response to infections, and these Cells increase their surface expression of HLA-DR. We have studied this parameter (HLA-DR+ ASC) in patients with recent diarrheal infection using immuno-magnetic Cell sorting and an enzyme linked immunospot (ELISPOT) technique that requires only one milliliter of blood. We validated this approach in adult patients with cholera (n = 15) or ETEC diarrhea (n = 30) on days 2, 7 and 30 after showing clinical symptom at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) hospital in Dhaka, and we compared responses to age-matched healthy controls (n = 7). We found that HLA-DR+ ASC (DR+ASC) responses specific both for T Cell-dependent (cholera toxin B subunit), and T Cell-independent (lipopolysaccharide) antigens were elevated at day 7 after showing clinical cholera symptom. Similarly, DR+ASCs were elevated against both heat-labile toxin and colonization factors following ETEC infection. We observed significant correlations between antigen-specific DR+ASC responses and antigen-specific, gut homing ASC and plasma Antibody responses. This study demonstrates that a simple ELISPOT procedure allows determination of antigen-specific ASC responses using a small volume of whole blood following diarrhea. This technique may be particularly useful in studying DR+ASC responses in young children and infants, either following infection or vaccination.
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kinetics of Antibody Secreting Cell and fecal iga responses after oral cholera vaccination in different age groups in a cholera endemic country
Vaccine, 2017Co-Authors: Marjahan Akhtar, Ann-mari Svennerholm, Firdausi Qadri, Taufiqur Rahman Bhuiyan, Sarmin Akter, Tanzeem Ahmed Rafique, Arifuzzaman Khan, Laila N Islam, Amit Saha, Anna LundgrenAbstract:Immune responses to oral enteric vaccines in children and infants may be influenced by factors such as age, previous priming with related microorganisms and breast feeding. In this study, we aimed to determine optimal time points to assess immune responses to oral enteric vaccines in different clinical specimens. This was done by investigating Antibody Secreting Cell (ASC) and fecal Antibody responses on different days after vaccination using the licensed oral cholera vaccine Dukoral, containing cholera toxin B-subunit (rCTB) and inactivated Vibrio cholerae bacteria, as a model vaccine. Two vaccine doses were given 2weeks apart to infants (6-11months), young children (12-18months), toddlers (19months-5years) and adults in a cholera endemic country (Bangladesh). IgA ASC responses, as determined by the antibodies in lymphocyte supernatant (ALS) assay, plasma IgA and IgG responses and secretory IgA (SIgA) responses in extracts of fecal samples were evaluated 4/5 and 7days after each vaccination. After the first vaccine dose, anti-CTB ALS IgA responses in adults and toddlers were high and comparable on day 5 and 7, while responses were low and infrequent in young children. After the second dose, highest ALS responses were detected on day 5 among the time points studied in all age groups and the responses declined until day 7. In contrast, plasma IgA and IgG anti-CTB responses were high both on day 5 and 7 after the second dose. Fecal SIgA responses in young children and infants were highest on day 7 after the second dose. Our results suggest that ASC/ALS responses to two doses of the oral cholera vaccine Dukoral and related oral vaccines should be analyzed earlier than previously recommended (day 7) at all ages. Fecal Antibody responses should preferably be analyzed later than ASC/ALS responses to detect the highest Antibody responses.
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induction of long term mucosal immunological memory in humans by an oral inactivated multivalent enterotoxigenic escherichia coli vaccine
Vaccine, 2016Co-Authors: Anna Lundgren, Marianne Jertborn, Ann-mari SvennerholmAbstract:Abstract We have evaluated the capacity of an oral multivalent enterotoxigenic Escherichia coli (ETEC) vaccine (MEV) to induce mucosal immunological memory. MEV consists of four inactivated E. coli strains over-expressing the major colonization factors (CFs) CFA/I, CS3, CS5 and CS6 and the LTB-related toxoid LCTB A . Memory responses were analyzed by comparing the magnitudes and kinetics of intestine-derived Antibody-Secreting Cell responses to a single dose of MEV in three groups of adult Swedish volunteers ( n = 16–19 subjects per group) in a Phase I trial: non-immunized controls (I) and subjects who in a previous Phase I trial 13–23 months earlier had received two biweekly doses of MEV (II) or MEV + double mutant LT (dmLT) adjuvant (III). Responses against CFs and LTB were analyzed in antibodies in lymphocyte secretions (ALS) of blood mononuclear Cells collected before (day 0) and 4/5 and 7 days after immunization. Specific circulating memory B Cells present at the time of the single dose vaccination were also studied to determine if such Cells may reflect mucosal memory. Considerably higher and significantly more frequent IgA ALS responses against all CFs and LTB were induced by the single vaccine dose in the previously immunized than in non-immunized volunteers. Furthermore, peak IgA ALS responses against all antigens were observed on days 4/5 in most of the previously immunized subjects whereas only a few previously non-vaccinated individuals responded before day 7. Priming with adjuvant did not influence memory responses. Circulating vaccine specific IgA memory B Cells were not detected, whereas anti-toxin IgG memory B Cells were identified 13–23 months after priming vaccination. We conclude that MEV induces functional mucosal immunological memory which remains at least 1–2 years. Furthermore, our results support that analysis of Antibody-Secreting Cell responses after booster vaccination may be a useful approach to evaluate longstanding mucosal immunological memory in humans. Clinical trials registration: ISRCTN27096290.
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different kinetics of circulating Antibody Secreting Cell responses after primary and booster oral immunizations a tool for assessing immunological memory
Vaccine, 2013Co-Authors: Susannah Leach, Anna Lundgren, Ann-mari SvennerholmAbstract:Abstract We show that the kinetics of circulating IgA as well as IgG Antibody-Secreting Cell (ASC) responses differs considerably after primary and booster vaccination with the oral cholera vaccine Dukoral®, as determined by the Antibody in lymphocyte supernatant (ALS) as well as ELISPOT methods. Thus, whereas the antitoxin ASC responses did not peak until 7–9 days after primary vaccination, peak responses to a second dose given after two weeks, or a single booster dose given 6 months to 14 years later, were recorded already after 4–5 days and then rapidly declined. Our results indicate that many previous studies reporting ASC results 7–10 days after repeated immunization may have substantially underestimated the magnitudes of the responses. The results also suggest that detection of peak ASC responses at an early time point after booster immunization can be used as a simple tool to assess immunological memory.
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robust gut associated vaccine specific Antibody Secreting Cell responses are detected at the mucosal surface of bangladeshi subjects after immunization with an oral killed bivalent v cholerae o1 o139 whole Cell cholera vaccine comparison with other m
Vaccine, 2009Co-Authors: Sohel Shamsuzzaman, Ann-mari Svennerholm, Tanvir Ahmed, Kaiissar Mannoor, Yasmin Ara Begum, Pradip Kumar Bardhan, Bradley R Sack, David A Sack, Jan HolmgrenAbstract:Abstract The emergence of V. cholerae O139 serogroup of V. cholerae capable of causing severe dehydrating cholera has over the decade led to efforts in formulation of vaccines to protect against this pathogen. Although the prevalence of diarrhea due to V. cholerae O139 has recorded a decrease, efforts on vaccine development continues to formulate an oral vaccine capable of stimulating the gut mucosal system. We have studied the mucosal immunogenicity in Bangladeshi adults to a killed whole Cell (WC) bivalent cholera vaccine composed of V. cholerae O139 as well as V. cholerae O1 strains together with the recombinant cholera toxin B subunit (CTB) (WC-O1/O139/CTB) and compared the immune responses to that obtained with the licensed monovalent cholera vaccine, Dukoral (WC-O1/CTB). Direct estimation of the WC-O1/O139/CTB vaccine-specific mucosal responses were carried out using lymphocytes isolated from duodenal biopsies, intestinal lavage fluid and feces. The vaccine induced robust Antibody-Secreting Cell responses in the duodenum specific to CTB as well as the O1 and O139 lipopolysaccharide (LPS). Magnitude of response was higher in the gut than in the circulation in all three Antibody isotypes. The CTB and LPS-specific mucosal Antibody responses were also seen in intestinal lavage fluid and fecal extracts. Vibriocidal Antibody responses in plasma were observed to both the V. cholerae O1 and O139 serogroups (76% and 57% response rates, respectively). Plasma IgA and IgG responses to CTB and IgA responses to both O1 and O139 LPS were elevated. The immune responses were comparable to that seen to the monovalent WC-O1/CTB recipients in all components studied. Overall, the bivalent cholera vaccine induces strong mucosal responses and the addition of the O139 component does not interfere with the responses to the licensed vaccine Dukoral. This sets the ground for testing such vaccines in large field trials in Bangladesh and also demonstrates that addition of other vibrio components to the existing cholera vaccine does not alter the responses to the O1 vaccine components.
Jan Holmgren - One of the best experts on this subject based on the ideXlab platform.
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robust gut associated vaccine specific Antibody Secreting Cell responses are detected at the mucosal surface of bangladeshi subjects after immunization with an oral killed bivalent v cholerae o1 o139 whole Cell cholera vaccine comparison with other m
Vaccine, 2009Co-Authors: Sohel Shamsuzzaman, Ann-mari Svennerholm, Tanvir Ahmed, Kaiissar Mannoor, Yasmin Ara Begum, Pradip Kumar Bardhan, Bradley R Sack, David A Sack, Jan HolmgrenAbstract:Abstract The emergence of V. cholerae O139 serogroup of V. cholerae capable of causing severe dehydrating cholera has over the decade led to efforts in formulation of vaccines to protect against this pathogen. Although the prevalence of diarrhea due to V. cholerae O139 has recorded a decrease, efforts on vaccine development continues to formulate an oral vaccine capable of stimulating the gut mucosal system. We have studied the mucosal immunogenicity in Bangladeshi adults to a killed whole Cell (WC) bivalent cholera vaccine composed of V. cholerae O139 as well as V. cholerae O1 strains together with the recombinant cholera toxin B subunit (CTB) (WC-O1/O139/CTB) and compared the immune responses to that obtained with the licensed monovalent cholera vaccine, Dukoral (WC-O1/CTB). Direct estimation of the WC-O1/O139/CTB vaccine-specific mucosal responses were carried out using lymphocytes isolated from duodenal biopsies, intestinal lavage fluid and feces. The vaccine induced robust Antibody-Secreting Cell responses in the duodenum specific to CTB as well as the O1 and O139 lipopolysaccharide (LPS). Magnitude of response was higher in the gut than in the circulation in all three Antibody isotypes. The CTB and LPS-specific mucosal Antibody responses were also seen in intestinal lavage fluid and fecal extracts. Vibriocidal Antibody responses in plasma were observed to both the V. cholerae O1 and O139 serogroups (76% and 57% response rates, respectively). Plasma IgA and IgG responses to CTB and IgA responses to both O1 and O139 LPS were elevated. The immune responses were comparable to that seen to the monovalent WC-O1/CTB recipients in all components studied. Overall, the bivalent cholera vaccine induces strong mucosal responses and the addition of the O139 component does not interfere with the responses to the licensed vaccine Dukoral. This sets the ground for testing such vaccines in large field trials in Bangladesh and also demonstrates that addition of other vibrio components to the existing cholera vaccine does not alter the responses to the O1 vaccine components.
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Enteric Infections in an Endemic Area Induce a Circulating Antibody-Secreting Cell Response with Homing Potentials to Both Mucosal and Systemic Tissues
The Journal of infectious diseases, 1998Co-Authors: Firdausi Qadri, Jan Holmgren, Kaiissar Mannoor, P. Helena Mäkelä, M. John Albert, Anu Kantele, Debasish Saha, M. A. Salam, Jussi M. KanteleAbstract:Enteric infections induce a response of circulating pathogen-specific Antibody-Secreting Cells (ASC). The expression of homing receptors (HRs) on these Cells was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an area in which cholera is endemic. The gut HR, alpha4beta7, was expressed by approximately 80% of the ASC, indicating mucosal homing of these Cells. However, the peripheral lymph node HR, L-selectin, was also expressed by approximately 80% of the ASC specific to either cholera toxin or O antigen. In earlier findings after oral immunization in nonendemic areas, alpha4beta7 has been expressed by approximately 100% and L-selectin by approximately 50% of the ASC. In comparison, the present data speak for a more systemic targeting of the immune response associated with long-lasting immunity in an endemic area. The results thus provide insight for the continued development and evaluation of vaccines.
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Immunological memory after immunization with oral cholera B subunit-whole-Cell vaccine in Swedish volunteers
Vaccine, 1994Co-Authors: Marianne Jertborn, Ann-mari Svennerholm, Jan HolmgrenAbstract:Abstract The capacity of peroral immunization with either two or three doses of B subunit-whole Cell (B-WC) cholera vaccine to induce immunological memory was examined in Swedish volunteers by testing the immune responses to a single dose of B-WC vaccine given 10 months after the initial immunization. Antibody responses in serum and Antibody-Secreting Cell (ASC) responses in peripheral blood were studied, since these responses seem to reflect the gut mucosal IgA immune responses after oral immunization with B-WC vaccine. Previously immunized volunteers responded to a single dose of B-WC vaccine more frequently and with higher levels of IgA and IgG antitoxin antibodies as well as vibriocidal antibodies in serum than did previously unvaccinated controls. The IgA-ASC responses to cholera toxin B subunit were also higher in primed volunteers than in controls. Two doses of B-WC vaccine were as effective as three doses in inducing immunological memory for cholera immunity. A new B-WC cholera vaccine based on recombinant B subunit had the same capacity as the first generation of B-WC vaccine to induce immunological memory for cholera antitoxin immunity.
Ashraful Islam Khan - One of the best experts on this subject based on the ideXlab platform.
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Antibody Secreting Cell responses after vibrio cholerae o1 infection and oral cholera vaccination in adults in bangladesh
Clinical and Vaccine Immunology, 2013Co-Authors: Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Fahima Chowdhury, Atiqur Rahman, Rasheduzzaman Rashu, Kamrul Islam, Regina C Larocque, Jens WrammertAbstract:Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (CruCell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the Cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.
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comparison of memory b Cell Antibody Secreting Cell and plasma Antibody responses in young children older children and adults with infection caused by vibrio cholerae o1 el tor ogawa in bangladesh
Clinical and Vaccine Immunology, 2011Co-Authors: Daniel T Leung, Mohammad Arif Rahman, M Mohasin, Asrafuzzaman M Riyadh, Sweta M Patel, Mohammad Murshid Alam, Fahima Chowdhury, Ashraful Islam KhanAbstract:Children bear a large component of the global burden of cholera. Despite this, little is known about immune responses to cholera in children, especially those under 5 years of age. Cholera vaccine studies have demonstrated lower long-term protective efficacy in young children than in older children and adults. Memory B Cell (MBC) responses may correlate with duration of protection following infection and vaccination. Here we report a comparison of immune responses in young children (3 to 5 years of age; n 17), older children (6 to 17 years of age; n 17), and adults (18 to 60 years of age; n 68) hospitalized with cholera in Dhaka, Bangladesh. We found that young children had lower baseline vibriocidal Antibody titers and higher fold increases in titer between day 2 and day 7 than adults. Young children had higher baseline IgG plasma Antibody levels to Vibrio cholerae antigens, although the magnitudes of responses at days 7 and 30 were similar across age groups. As a surrogate marker for mucosal immune responses, we assessed day 7 Antibody-Secreting Cell (ASC) responses. These were comparable across age groups, although there was a trend for older age groups to have higher levels of lipopolysaccharide-specific IgA ASC responses. All age groups developed comparable MBC responses to V. cholerae lipopolysaccharide and cholera toxin B subunit at day 30. These findings suggest that young children are able to mount robust vibriocidal, plasma Antibody, ASC, and MBC responses against V. cholerae O1, suggesting that under an optimal vaccination strategy, young children could achieve protective efficacy comparable to that induced in adults. Cholera is an acute dehydrating diarrheal disease caused predominantly by the Vibrio cholerae O1 or O139 serogroup. Globally, the vast majority of cholera is caused by V. cholerae O1. Cholera is endemic in over 50 countries and affects 3 to 5 million people each year, causing more than 100,000 deaths (2, 41). In areas of the world in which cholera is endemic, children under 5 years of age have the highest burden of disease (12, 31), and during cholera epidemics, children and adults are both at risk of dehydrating illness (21, 24, 34). In a rural area of Bangladesh in which cholera is endemic, 80% of the population had detectable vibriocidal antibodies by the age of 15 years (26). Similarly, in a recent observational study in urban Bangladesh, household contacts of patients with V. cholerae O1 infection who were 5 years of age had a significantly higher risk of developing infection than older family members in a 21-day observational period following identification of the index household case (15).
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development of immunoglobulin m memory to both a t Cell independent and a t Cell dependent antigen following infection with vibrio cholerae o1 in bangladesh
Infection and Immunity, 2010Co-Authors: Emily A Kendall, Ashraful Islam Khan, Mohammad Murshid Alam, Fahima Chowdhury, Regina C Larocque, Abdullah A Tarique, Azim Hossain, Mohammad Arifuzzaman, Nayeema Akhtar, Jason B HarrisAbstract:Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B Cells of the immunoglobulin G (IgG) and IgA isotypes to V. cholerae O1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B Cells of the IgM isotype may play a role in long-term protection, particularly against T-Cell-independent antigens, but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we assayed acute- and convalescent-phase blood samples from cholera patients for the presence of memory B Cells that produce cholera antigen-specific IgM Antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and Antibody-Secreting Cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-Cell-independent antigen LPS and to the T-Cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM Antibody-Secreting Cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma Antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma Antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.
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antigen specific immunoglobulin a antibodies secreted from circulating b Cells are an effective marker for recent local immune responses in patients with cholera comparison to Antibody Secreting Cell responses and other immunological markers
Infection and Immunity, 2003Co-Authors: Firdausi Qadri, David A Sack, Edward T Ryan, A S G Faruque, Firoz Ahmed, Ashraful Islam Khan, Md Monirul Islam, S M Akramuzzaman, Stephen B CalderwoodAbstract:Gut-derived lymphocytes transiently migrate through the peripheral circulation before homing back to mucosal sites and can be detected using an ELISPOT-based Antibody Secreting Cell (ASC) assay. Alternatively, transiently circulating lymphocytes may be cultured in vitro, and culture supernatants may be assayed for antigen-specific responses (Antibody in lymphocyte supernatant [ALS] assay). The ALS assay has not been validated extensively in natural mucosal infection, nor has the ALS response been compared to the ASC assay and other cholera-specific immunological responses. Accordingly, we examined immune responses in 30 adult patients with acute cholera in Bangladesh, compared with 10 healthy controls, measuring ALS-immunoglobulin A (IgA), ASC-IgA, and serum and fecal IgA responses to two potent Vibrio cholerae immunogens, the nontoxic B subunit of cholera toxin (CtxB) and lipopolysaccharide (LPS) and a weaker V. cholerae immunogen, the mannose-sensitive hemagglutinin (MSHA). We found significant increases of anti-CtxB, anti-LPS, and anti-MSHA IgA in supernatants of lymphocytes cultured 7 days after onset of cholera using the ALS assay. We found that ALS and ASC responses correlated extremely well; both had comparable sensitivities as the vibriocidal responses, and both procedures were more sensitive than fecal IgA measurements. An advantage of the ALS assay for studying mucosal immune responses is the ability to freeze antibodies in supernatants for subsequent evaluation; like the ASC assay, the ALS assay can distinguish recent from remote mucosal infection, a distinction that may be difficult to make in endemic settings using other procedures.
Fahima Chowdhury - One of the best experts on this subject based on the ideXlab platform.
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immune responses to o specific polysaccharide and lipopolysaccharide of vibrio cholerae o1 ogawa in adult bangladeshi recipients of an oral killed cholera vaccine and comparison to responses in patients with cholera
American Journal of Tropical Medicine and Hygiene, 2014Co-Authors: Taher Uddin, Daniel T Leung, Mohammad Murshid Alam, Atiqur Rahman, Amena Aktar, Russell A Johnson, Arifur M Rahman, Sadia Afrin, Aklima Akter, Fahima ChowdhuryAbstract:Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific poly- saccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA Antibody and Antibody Secreting Cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detect- able IgA, IgM, and IgG memory B Cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection.
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Antibody Secreting Cell responses after vibrio cholerae o1 infection and oral cholera vaccination in adults in bangladesh
Clinical and Vaccine Immunology, 2013Co-Authors: Edward T Ryan, Taufiqur Rahman Bhuiyan, Ashraful Islam Khan, Fahima Chowdhury, Atiqur Rahman, Rasheduzzaman Rashu, Kamrul Islam, Regina C Larocque, Jens WrammertAbstract:Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V. cholerae infection using a flow cytometrically defined population and compared V. cholerae-specific responses in adult patients with V. cholerae O1 infection and vaccinees who received the OCV Dukoral (CruCell Vaccines Canada). Among flow cytometrically sorted populations of gut-homing plasmablasts, almost 50% of the Cells recognized either cholera toxin B subunit (CtxB) or V. cholerae O1 lipopolysaccharide (LPS). Using a traditional enzyme-linked immunosorbent spot assay (ELISPOT), we found that infection with V. cholerae O1 and OCVs induce similar responses to the protein antigen CtxB, but responses to LPS were diminished after OCV compared to those after natural V. cholerae infection. A second dose of OCV on day 14 failed to boost circulating V. cholerae-specific plasmablast responses in Bangladeshi adults. Our results differ from those in studies from areas where cholera is not endemic, in which a second vaccination on day 14 significantly boosts plasmablast responses. Given these results, it is likely that the optimal boosting strategies for OCVs differ significantly between areas where V. cholerae infection is endemic and those where it is not.
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comparison of memory b Cell Antibody Secreting Cell and plasma Antibody responses in young children older children and adults with infection caused by vibrio cholerae o1 el tor ogawa in bangladesh
Clinical and Vaccine Immunology, 2011Co-Authors: Daniel T Leung, Mohammad Arif Rahman, M Mohasin, Asrafuzzaman M Riyadh, Sweta M Patel, Mohammad Murshid Alam, Fahima Chowdhury, Ashraful Islam KhanAbstract:Children bear a large component of the global burden of cholera. Despite this, little is known about immune responses to cholera in children, especially those under 5 years of age. Cholera vaccine studies have demonstrated lower long-term protective efficacy in young children than in older children and adults. Memory B Cell (MBC) responses may correlate with duration of protection following infection and vaccination. Here we report a comparison of immune responses in young children (3 to 5 years of age; n 17), older children (6 to 17 years of age; n 17), and adults (18 to 60 years of age; n 68) hospitalized with cholera in Dhaka, Bangladesh. We found that young children had lower baseline vibriocidal Antibody titers and higher fold increases in titer between day 2 and day 7 than adults. Young children had higher baseline IgG plasma Antibody levels to Vibrio cholerae antigens, although the magnitudes of responses at days 7 and 30 were similar across age groups. As a surrogate marker for mucosal immune responses, we assessed day 7 Antibody-Secreting Cell (ASC) responses. These were comparable across age groups, although there was a trend for older age groups to have higher levels of lipopolysaccharide-specific IgA ASC responses. All age groups developed comparable MBC responses to V. cholerae lipopolysaccharide and cholera toxin B subunit at day 30. These findings suggest that young children are able to mount robust vibriocidal, plasma Antibody, ASC, and MBC responses against V. cholerae O1, suggesting that under an optimal vaccination strategy, young children could achieve protective efficacy comparable to that induced in adults. Cholera is an acute dehydrating diarrheal disease caused predominantly by the Vibrio cholerae O1 or O139 serogroup. Globally, the vast majority of cholera is caused by V. cholerae O1. Cholera is endemic in over 50 countries and affects 3 to 5 million people each year, causing more than 100,000 deaths (2, 41). In areas of the world in which cholera is endemic, children under 5 years of age have the highest burden of disease (12, 31), and during cholera epidemics, children and adults are both at risk of dehydrating illness (21, 24, 34). In a rural area of Bangladesh in which cholera is endemic, 80% of the population had detectable vibriocidal antibodies by the age of 15 years (26). Similarly, in a recent observational study in urban Bangladesh, household contacts of patients with V. cholerae O1 infection who were 5 years of age had a significantly higher risk of developing infection than older family members in a 21-day observational period following identification of the index household case (15).
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development of immunoglobulin m memory to both a t Cell independent and a t Cell dependent antigen following infection with vibrio cholerae o1 in bangladesh
Infection and Immunity, 2010Co-Authors: Emily A Kendall, Ashraful Islam Khan, Mohammad Murshid Alam, Fahima Chowdhury, Regina C Larocque, Abdullah A Tarique, Azim Hossain, Mohammad Arifuzzaman, Nayeema Akhtar, Jason B HarrisAbstract:Vibrio cholerae O1 can cause severe watery diarrhea that can be life-threatening without treatment. Infection results in long-lasting protection against subsequent disease. Development of memory B Cells of the immunoglobulin G (IgG) and IgA isotypes to V. cholerae O1 antigens, including serotype-specific lipopolysaccharide (LPS) and the B subunit of cholera toxin (CTB), after cholera infection has been demonstrated. Memory B Cells of the IgM isotype may play a role in long-term protection, particularly against T-Cell-independent antigens, but IgM memory has not been studied in V. cholerae O1 infection. Therefore, we assayed acute- and convalescent-phase blood samples from cholera patients for the presence of memory B Cells that produce cholera antigen-specific IgM Antibody upon polyclonal stimulation in in vitro culture. We also examined the development of serological and Antibody-Secreting Cell responses following infection. Subjects developed significant IgM memory responses by day 30 after infection, both to the T-Cell-independent antigen LPS and to the T-Cell-dependent antigen CTB. No significant corresponding elevations in plasma IgM antibodies or circulating IgM Antibody-Secreting Cells to CTB were detected. In 17 subjects followed to day 90 after infection, significant persistence of elevated IgM memory responses was not observed. The IgM memory response to CTB was negatively correlated with the IgG plasma Antibody response to CTB, and there was a trend toward negative correlation between the IgM memory and IgA plasma Antibody responses to LPS. We did not observe an association between the IgM memory response to LPS and the vibriocidal titer.
Tzou Yien Lin - One of the best experts on this subject based on the ideXlab platform.
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a potent virus specific Antibody Secreting Cell response to acute enterovirus 71 infection in children
The Journal of Infectious Diseases, 2015Co-Authors: Kuanying A Huang, Jainn Jim Lin, Chenghsun Chiu, Shuan Yang, Kuo Chien Tsao, Yhu Chering Huang, Tzou Yien LinAbstract:BACKGROUND Enterovirus 71 (EV71) remains a leading pathogen for acute infectious diseases in children, especially in Asia. The Cellular basis for establishing a virus-specific Antibody response to acute EV71 infections is unclear in children. METHODS We studied the magnitude of virus-specific Antibody-Secreting B Cells (ASCs) and its relationship with serological response, clinical parameters, and virological parameters among children with laboratory-confirmed EV71 infection. RESULTS A potent EV71 genogroup B- and virus-specific ASC response was detected in the first week of illness among genotype B5 EV71-infected children. The cross-reactive EV71-specific ASC response to genogroup C viral antigens composed about 10% of the response. The EV71-specific ASC response in children aged ≥3 years produced immunoglobulin G predominantly, but immunoglobulin M was predominant in younger children. Proliferation marker was expressed by the majority of circulating ASCs in the acute phase of EV71 infection. Virus-specific ASC responses significantly correlated with throat viral load, fever duration, and serological genogroup-specific neutralization titer. CONCLUSIONS The presence of a virus-specific ASC response serves an early Cellular marker of an EV71-specific Antibody response. Further detailed study of EV71-specific ASCs at the monoclonal level is crucial to delineate the specificity and function of Antibody immunity in children.
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virus specific Antibody Secreting Cell memory b Cell and sero Antibody responses in the human influenza challenge model
The Journal of Infectious Diseases, 2014Co-Authors: Kuanying A Huang, Tzou Yien Lin, Elizabeth A Clutterbuck, Cecilia Chui, Tom Wilkinson, Anthony Gilbert, John S Oxford, Rob Lambkinwilliams, Andrew J McmichaelAbstract:Background Antibodies play a major role in the protection against influenza virus in human. However, the Antibody level is usually short-lived and the Cellular mechanisms underlying influenza virus-specific Antibody response to acute infection remain unclear. Methods We studied the kinetics and magnitude of influenza virus-specific B-Cell and serum Antibody responses in relation to virus replication during the course of influenza infection in healthy adult volunteers who were previously seronegative and experimentally infected with seasonal influenza H1N1 A/Brisbane/59/07 virus. Results Our data demonstrated a robust expansion of the virus-specific Antibody-Secreting Cells (ASCs) and memory B Cells in the peripheral blood, which correlated with both the throat viral load and the duration of viral shedding. The ASC response was obviously detected on day 7 post-infection when the virus was completely cleared from nasal samples, and serum hemagglutination-inhibition antibodies were still undetectable. On day 28 postinfection, influenza virus-specific B Cells were further identified from the circulating compartment of isotype-switched B Cells. Conclusions Virus-specific ASCs could be the earliest marker of B-Cell response to a new flu virus infection, such as H7N9 in humans.