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Anu Kantele - One of the best experts on this subject based on the ideXlab platform.
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specific and cross reactive immune response to oral salmonella typhi ty21a and parenteral vi capsular polysaccharide typhoid vaccines administered concomitantly
Vaccine, 2015Co-Authors: Sari H Pakkanen, Jussi M Kantele, Laura E Savolainen, Lars Rombo, Anu KanteleAbstract:Abstract Background Since protective efficacy of the current typhoid vaccines—oral whole-cell S almonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation—is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae , if administered concomitantly. Materials and methods Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a + Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive Plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive with S . Typhi, S . Paratyphi A/B/C, or selected NTS serotypes ( S . Enteritidis, S . Typhimurium). Results In the Ty21a + Vi group, no specific or cross-reactive Plasmablasts were detected before vaccination. After vaccination, the number of S . Typhi-specific Plasmablasts (878 ASC/10 6 PBMC, 95%CI 554–1201) proved higher than in the Ty21a (339 ASC/10 6 PBMC; p 6 PBMC; p S . Paratyphi A/B, S . Enteritidis and S . Typhimurium p S . Paratyphi C p S . Paratyphi C not significant, others p Conclusions Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific Plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes. The data encourage concomitant use of Ty21 and Vi vaccines for those at risk.
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cross reactive immune response induced by the vi capsular polysaccharide typhoid vaccine against salmonella paratyphi strains
Scandinavian Journal of Immunology, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Anu KanteleAbstract:There are no vaccines in clinical use against paratyphoid fever, caused by Salmonella Paratyphi A and B or, rarely, C. Oral Salmonella Typhi Ty21a typhoid vaccine elicits a significant cross-reactive immune response against S. Paratyphi A and B, and some reports suggest cross-protective efficacy against the disease. These findings are ascribed to the O-12 antigen shared between the strains. The Vi capsular polysaccharide vaccine has been shown to elicit antibodies reactive with O-9,12. Twenty-five volunteers immunized with the parenteral Vi vaccine (Typherix®) were explored for Plasmablasts cross-reactive with paratyphoid strains; the responses were compared to those in 25 age- and gender-matched volunteers immunized with Ty21a (Vivotif®). Before vaccination, 48/50 vaccinees had no Plasmablasts reactive with the antigens. Seven days after vaccination, 15/25 and 22/25 Vi- and Ty21a-vaccinated volunteers had circulating Plasmablasts producing antibodies cross-reactive with S. Paratyphi A, 18/25 and 23/25 with S. Paratyphi B and 16/25 and 9/25 with Paratyphi C, respectively. Compared to the Ty21a group, the Vi group showed significantly lower responses to S. Paratyphi A and B and higher to S. Paratyphi C. To conclude, the Vi vaccine elicited a cross-reactive Plasmablast response to S. Paratyphi C (Vi antigen in common) and less marked responses to S. Paratyphi A and B than the Ty21a preparation. S. Paratyphi A and B both being Vi-negative, the result can be explained by trace amounts of bacterial cell wall O-12 antigen in the Vi preparation, despite purification. The clinical significance of this finding remains to be determined.
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cross reactive immune response elicited by parenteral vi polysaccharide typhoid vaccine against non typhoid salmonellae
Vaccine, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Christian Herzog, Anu KanteleAbstract:Despite 155000 deaths and over 90 million cases - and the current emergence of antimicrobial resistance - no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine.; Volunteers immunized with the Vi polysaccharide (Typherix(®); n=25) were investigated for circulating Plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif(®)), as partly presented in our previous study. The cross-reactive Plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions.; 49 out of 50 vaccinees showed a cross-reactive Plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19-55 and 363: 234-493 Plasmablasts/10(6) PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8-38 and 222: 105-338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive Plasmablasts elicited by the Vi vaccine had systemic homing properties.; The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.
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live oral typhoid vaccine salmonella typhi ty21a a surrogate vaccine against non typhoid salmonella
Vaccine, 2012Co-Authors: Anu Kantele, Sari H Pakkanen, Anja Siitonen, Riitta Karttunen, Jussi M KanteleAbstract:Abstract Background Non-typhoid Salmonella (NTS) is a leading cause of food-borne illness with more than 90 million annual cases and an emerging antimicrobial resistance among the strains worldwide. Paradoxically, no vaccines are available against these pathogens. Numerous NTS strains share surface O-antigens with Salmonella enterica serotype Typhi. As intestinal antibodies against O-antigens have proven protective against NTS in animal experiments, it appears conceivable that the oral whole-cell typhoid vaccine, Salmonella Typhi Ty21a (Vivotif ® ), which effectively elicits intestinal antibodies against O-antigens, could exhibit cross-protective efficacy against NTS. We sought immunological evidence in support of cross-protective efficacy of Ty21a against NTS. Materials and methods 35 volunteers receiving Ty21a vaccine and five patients with enteric fever were investigated with ELISPOT for circulating Plasmablasts secreting antibodies reactive with Salmonella Typhi and six different NTS serotypes. These Plasmablasts were also analysed for homing receptor expressions. Results In all vaccinees and patients, a strong gut-directed cross-reactive Plasmablast response was found against serotypes sharing the two O-antigens with Salmonella Typhi (O-9,12) (in vaccinees, mean: 95%CI 268: 228–508 and 363: 234–493 Plasmablasts/10 6 PBMC against Salmonella Typhi and Enteritidis). Responses against strains sharing one O-antigen (O-12) were weaker (222: 105–338 against Salmonella Typhimurium), while no significant reactivity was detected against strains without typhoidal O-antigens. Conclusions Intestinal antibodies against O-antigens protect against NTS in animal experiments. Ty21a was found to elicit intestinal immune responses cross-reactive with NTS strains sharing O-antigens with Ty21a. These include the most common NTS, Salmonella Enteritidis and Typhimurium. The data suggest that Ty21a may have cross-protective efficacy against numerous NTS strains.
Jens Wrammert - One of the best experts on this subject based on the ideXlab platform.
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Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine
Vaccines, 2020Co-Authors: Evan J. Anderson, Heather Hill, Johannes B. Goll, Lilin Lai, Jens Wrammert, Sarah Kabbani, Lalita Priyamvada, Travis L. Jensen, Carol KaoAbstract:Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cTFH) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-naive adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH, and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 Plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 Plasmablasts. CD4+ peaked at Day 29 and one-third produced ≥2 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines.
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Pre-Existing Dengue Immunity Drives a DENV-Biased Plasmablast Response in ZIKV-Infected Patient
'MDPI AG', 2018Co-Authors: Siddhartha K. Bhaumik, Nadine Rouphael, Lilin Lai, Lalita Priyamvada, Alice Cho, Robert C. Kauffman, Muktha S. Natrajan, Mehul S. Suthar, Mark J. Mulligan, Jens WrammertAbstract:The re-emergence of Zika virus (ZIKV) in the western hemisphere has most significantly affected dengue virus (DENV) endemic regions. Due to the geographical overlap between these two closely related flaviviruses, numerous individuals who suffered ZIKV infection during recent outbreaks may have also previously been exposed to DENV. As such, the impact of pre-existing dengue immunity on immune responses to ZIKV has been an area of focused research and interest. To understand how B cell responses to a ZIKV infection may be modulated by prior dengue exposures, we compared and contrasted Plasmablast repertoire and specificity between two ZIKV-infected individuals, one dengue-naïve (ZK018) and the other dengue-experienced (ZK016). In addition to examining serological responses, we generated 59 patient Plasmablast-derived monoclonal antibodies (mAbs) to define the heterogeneity of the early B cell response to ZIKV. Both donors experienced robust ZIKV-induced Plasmablast expansions early after infection, with comparable mutational frequencies in their antibody variable genes. However, notable differences were observed in Plasmablast clonality and functional reactivity. Plasmablasts from the dengue-experienced donor ZK016 included cells with shared clonal origin, while ZK018 mAbs were entirely clonally unrelated. Both at the mAb and plasma level, ZK016 antibodies displayed extensive cross-reactivity to DENV1-4, and preferentially neutralized DENV compared to ZIKV. In contrast, the neutralization activity of ZK018 mAbs was primarily directed towards ZIKV, and fewer mAbs from this donor were cross-reactive, with the cross-reactive phenotype largely limited to fusion loop-specific mAbs. ZK016 antibodies caused greater enhancement of DENV2 infection of FcRγ-expressing cells overall compared to ZK018, with a striking difference at the plasma level. Taken together, these data strongly suggest that the breadth and protective capacity of the initial antibody responses after ZIKV infection may depend on the dengue immune status of the individual. These findings have implications for vaccine design, given the likelihood that future epidemics will involve both dengue-experienced and naïve populations
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vaccine induced Plasmablast responses in rhesus macaques phenotypic characterization and a source for generating antigen specific monoclonal antibodies
Journal of Immunological Methods, 2015Co-Authors: Eduardo Lani Volpe Da Silveira, Francois Villinger, Sudhir Pai Kasturi, Yevgeniy Kovalenkov, Ata Ur Rasheed, Patryce Yeiser, Zarpheen S Jinnah, Traci Legere, Bali Pulendran, Jens WrammertAbstract:Over 100 broadly neutralizing antibodies have been isolated from a minority of HIV infected patients, but the steps leading to the selection of plasma cells producing such antibodies remain incompletely understood, hampering the development of vaccines able to elicit them. Rhesus macaques have become a preferred animal model system used to study SIV/HIV, for the characterization and development of novel therapeutics and vaccines as well as to understand pathogenesis. However, most of our knowledge about the dynamics of antibody responses is limited to the analysis of serum antibodies or monoclonal antibodies generated from memory B cells. In a vaccine setting, relatively little is known about the early cellular responses that elicit long-lived plasma cells and memory B cells and the tools to dissect Plasmablast responses are not available in macaques. In the current study, we show that the majority (>80%) of the vaccine-induced Plasmablast response are antigen-specific by functional ELISPOT assays. While Plasmablasts are easily defined and isolated in humans, those same phenotypic markers have not been useful for identifying macaque Plasmablasts. Here we describe an approach that allows for the isolation and single cell sorting of vaccine-induced Plasmablasts. Finally, we show that isolated Plasmablasts can be used to efficiently recover antigen-specific monoclonal antibodies through single cell expression cloning. This will allow detailed studies of the early Plasmablast responses in rhesus macaques, enabling the characterization of both their repertoire breadth as well as the epitope specificity and functional qualities of the antibodies they produce, not only in the context of SIV/HIV vaccines but for many other pathogens/vaccines as well.
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dengue virus infection induces expansion of a cd14 cd16 monocyte population that stimulates Plasmablast differentiation
Cell Host & Microbe, 2014Co-Authors: Marcin Kwissa, Jens Wrammert, Helder I Nakaya, Nattawat Onlamoon, Francois Villinger, Guey Chuen Perng, Sutee Yoksan, Kovit PattanapanyasatAbstract:Summary Dengue virus (DENV) infection induces the expansion of Plasmablasts, which produce antibodies that can neutralize DENV but also enhance disease upon secondary infection with another DENV serotype. To understand how these immune responses are generated, we used a systems biological approach to analyze immune responses to dengue in humans. Transcriptomic analysis of whole blood revealed that genes encoding proinflammatory mediators and type I interferon-related proteins were associated with high DENV levels during initial symptomatic disease. Additionally, CD14 + CD16 + monocytes increased in the blood. Similarly, in a nonhuman primate model, DENV infection boosted CD14 + CD16 + monocyte numbers in the blood and lymph nodes. Upon DENV infection in vitro, monocytes upregulated CD16 and mediated differentiation of resting B cells to Plasmablasts as well as immunoglobulin G (IgG) and IgM secretion. These findings provide a detailed picture of innate responses to dengue and highlight a role for CD14 + CD16 + monocytes in promoting Plasmablast differentiation and anti-DENV antibody responses.
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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, 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.
Sari H Pakkanen - One of the best experts on this subject based on the ideXlab platform.
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specific and cross reactive immune response to oral salmonella typhi ty21a and parenteral vi capsular polysaccharide typhoid vaccines administered concomitantly
Vaccine, 2015Co-Authors: Sari H Pakkanen, Jussi M Kantele, Laura E Savolainen, Lars Rombo, Anu KanteleAbstract:Abstract Background Since protective efficacy of the current typhoid vaccines—oral whole-cell S almonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation—is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae , if administered concomitantly. Materials and methods Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a + Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive Plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive with S . Typhi, S . Paratyphi A/B/C, or selected NTS serotypes ( S . Enteritidis, S . Typhimurium). Results In the Ty21a + Vi group, no specific or cross-reactive Plasmablasts were detected before vaccination. After vaccination, the number of S . Typhi-specific Plasmablasts (878 ASC/10 6 PBMC, 95%CI 554–1201) proved higher than in the Ty21a (339 ASC/10 6 PBMC; p 6 PBMC; p S . Paratyphi A/B, S . Enteritidis and S . Typhimurium p S . Paratyphi C p S . Paratyphi C not significant, others p Conclusions Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific Plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes. The data encourage concomitant use of Ty21 and Vi vaccines for those at risk.
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cross reactive immune response induced by the vi capsular polysaccharide typhoid vaccine against salmonella paratyphi strains
Scandinavian Journal of Immunology, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Anu KanteleAbstract:There are no vaccines in clinical use against paratyphoid fever, caused by Salmonella Paratyphi A and B or, rarely, C. Oral Salmonella Typhi Ty21a typhoid vaccine elicits a significant cross-reactive immune response against S. Paratyphi A and B, and some reports suggest cross-protective efficacy against the disease. These findings are ascribed to the O-12 antigen shared between the strains. The Vi capsular polysaccharide vaccine has been shown to elicit antibodies reactive with O-9,12. Twenty-five volunteers immunized with the parenteral Vi vaccine (Typherix®) were explored for Plasmablasts cross-reactive with paratyphoid strains; the responses were compared to those in 25 age- and gender-matched volunteers immunized with Ty21a (Vivotif®). Before vaccination, 48/50 vaccinees had no Plasmablasts reactive with the antigens. Seven days after vaccination, 15/25 and 22/25 Vi- and Ty21a-vaccinated volunteers had circulating Plasmablasts producing antibodies cross-reactive with S. Paratyphi A, 18/25 and 23/25 with S. Paratyphi B and 16/25 and 9/25 with Paratyphi C, respectively. Compared to the Ty21a group, the Vi group showed significantly lower responses to S. Paratyphi A and B and higher to S. Paratyphi C. To conclude, the Vi vaccine elicited a cross-reactive Plasmablast response to S. Paratyphi C (Vi antigen in common) and less marked responses to S. Paratyphi A and B than the Ty21a preparation. S. Paratyphi A and B both being Vi-negative, the result can be explained by trace amounts of bacterial cell wall O-12 antigen in the Vi preparation, despite purification. The clinical significance of this finding remains to be determined.
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cross reactive immune response elicited by parenteral vi polysaccharide typhoid vaccine against non typhoid salmonellae
Vaccine, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Christian Herzog, Anu KanteleAbstract:Despite 155000 deaths and over 90 million cases - and the current emergence of antimicrobial resistance - no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine.; Volunteers immunized with the Vi polysaccharide (Typherix(®); n=25) were investigated for circulating Plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif(®)), as partly presented in our previous study. The cross-reactive Plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions.; 49 out of 50 vaccinees showed a cross-reactive Plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19-55 and 363: 234-493 Plasmablasts/10(6) PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8-38 and 222: 105-338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive Plasmablasts elicited by the Vi vaccine had systemic homing properties.; The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.
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live oral typhoid vaccine salmonella typhi ty21a a surrogate vaccine against non typhoid salmonella
Vaccine, 2012Co-Authors: Anu Kantele, Sari H Pakkanen, Anja Siitonen, Riitta Karttunen, Jussi M KanteleAbstract:Abstract Background Non-typhoid Salmonella (NTS) is a leading cause of food-borne illness with more than 90 million annual cases and an emerging antimicrobial resistance among the strains worldwide. Paradoxically, no vaccines are available against these pathogens. Numerous NTS strains share surface O-antigens with Salmonella enterica serotype Typhi. As intestinal antibodies against O-antigens have proven protective against NTS in animal experiments, it appears conceivable that the oral whole-cell typhoid vaccine, Salmonella Typhi Ty21a (Vivotif ® ), which effectively elicits intestinal antibodies against O-antigens, could exhibit cross-protective efficacy against NTS. We sought immunological evidence in support of cross-protective efficacy of Ty21a against NTS. Materials and methods 35 volunteers receiving Ty21a vaccine and five patients with enteric fever were investigated with ELISPOT for circulating Plasmablasts secreting antibodies reactive with Salmonella Typhi and six different NTS serotypes. These Plasmablasts were also analysed for homing receptor expressions. Results In all vaccinees and patients, a strong gut-directed cross-reactive Plasmablast response was found against serotypes sharing the two O-antigens with Salmonella Typhi (O-9,12) (in vaccinees, mean: 95%CI 268: 228–508 and 363: 234–493 Plasmablasts/10 6 PBMC against Salmonella Typhi and Enteritidis). Responses against strains sharing one O-antigen (O-12) were weaker (222: 105–338 against Salmonella Typhimurium), while no significant reactivity was detected against strains without typhoidal O-antigens. Conclusions Intestinal antibodies against O-antigens protect against NTS in animal experiments. Ty21a was found to elicit intestinal immune responses cross-reactive with NTS strains sharing O-antigens with Ty21a. These include the most common NTS, Salmonella Enteritidis and Typhimurium. The data suggest that Ty21a may have cross-protective efficacy against numerous NTS strains.
Jussi M Kantele - One of the best experts on this subject based on the ideXlab platform.
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specific and cross reactive immune response to oral salmonella typhi ty21a and parenteral vi capsular polysaccharide typhoid vaccines administered concomitantly
Vaccine, 2015Co-Authors: Sari H Pakkanen, Jussi M Kantele, Laura E Savolainen, Lars Rombo, Anu KanteleAbstract:Abstract Background Since protective efficacy of the current typhoid vaccines—oral whole-cell S almonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation—is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae , if administered concomitantly. Materials and methods Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a + Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive Plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive with S . Typhi, S . Paratyphi A/B/C, or selected NTS serotypes ( S . Enteritidis, S . Typhimurium). Results In the Ty21a + Vi group, no specific or cross-reactive Plasmablasts were detected before vaccination. After vaccination, the number of S . Typhi-specific Plasmablasts (878 ASC/10 6 PBMC, 95%CI 554–1201) proved higher than in the Ty21a (339 ASC/10 6 PBMC; p 6 PBMC; p S . Paratyphi A/B, S . Enteritidis and S . Typhimurium p S . Paratyphi C p S . Paratyphi C not significant, others p Conclusions Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific Plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes. The data encourage concomitant use of Ty21 and Vi vaccines for those at risk.
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cross reactive immune response induced by the vi capsular polysaccharide typhoid vaccine against salmonella paratyphi strains
Scandinavian Journal of Immunology, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Anu KanteleAbstract:There are no vaccines in clinical use against paratyphoid fever, caused by Salmonella Paratyphi A and B or, rarely, C. Oral Salmonella Typhi Ty21a typhoid vaccine elicits a significant cross-reactive immune response against S. Paratyphi A and B, and some reports suggest cross-protective efficacy against the disease. These findings are ascribed to the O-12 antigen shared between the strains. The Vi capsular polysaccharide vaccine has been shown to elicit antibodies reactive with O-9,12. Twenty-five volunteers immunized with the parenteral Vi vaccine (Typherix®) were explored for Plasmablasts cross-reactive with paratyphoid strains; the responses were compared to those in 25 age- and gender-matched volunteers immunized with Ty21a (Vivotif®). Before vaccination, 48/50 vaccinees had no Plasmablasts reactive with the antigens. Seven days after vaccination, 15/25 and 22/25 Vi- and Ty21a-vaccinated volunteers had circulating Plasmablasts producing antibodies cross-reactive with S. Paratyphi A, 18/25 and 23/25 with S. Paratyphi B and 16/25 and 9/25 with Paratyphi C, respectively. Compared to the Ty21a group, the Vi group showed significantly lower responses to S. Paratyphi A and B and higher to S. Paratyphi C. To conclude, the Vi vaccine elicited a cross-reactive Plasmablast response to S. Paratyphi C (Vi antigen in common) and less marked responses to S. Paratyphi A and B than the Ty21a preparation. S. Paratyphi A and B both being Vi-negative, the result can be explained by trace amounts of bacterial cell wall O-12 antigen in the Vi preparation, despite purification. The clinical significance of this finding remains to be determined.
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cross reactive immune response elicited by parenteral vi polysaccharide typhoid vaccine against non typhoid salmonellae
Vaccine, 2014Co-Authors: Sari H Pakkanen, Jussi M Kantele, Christian Herzog, Anu KanteleAbstract:Despite 155000 deaths and over 90 million cases - and the current emergence of antimicrobial resistance - no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine.; Volunteers immunized with the Vi polysaccharide (Typherix(®); n=25) were investigated for circulating Plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif(®)), as partly presented in our previous study. The cross-reactive Plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions.; 49 out of 50 vaccinees showed a cross-reactive Plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19-55 and 363: 234-493 Plasmablasts/10(6) PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8-38 and 222: 105-338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive Plasmablasts elicited by the Vi vaccine had systemic homing properties.; The Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.
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live oral typhoid vaccine salmonella typhi ty21a a surrogate vaccine against non typhoid salmonella
Vaccine, 2012Co-Authors: Anu Kantele, Sari H Pakkanen, Anja Siitonen, Riitta Karttunen, Jussi M KanteleAbstract:Abstract Background Non-typhoid Salmonella (NTS) is a leading cause of food-borne illness with more than 90 million annual cases and an emerging antimicrobial resistance among the strains worldwide. Paradoxically, no vaccines are available against these pathogens. Numerous NTS strains share surface O-antigens with Salmonella enterica serotype Typhi. As intestinal antibodies against O-antigens have proven protective against NTS in animal experiments, it appears conceivable that the oral whole-cell typhoid vaccine, Salmonella Typhi Ty21a (Vivotif ® ), which effectively elicits intestinal antibodies against O-antigens, could exhibit cross-protective efficacy against NTS. We sought immunological evidence in support of cross-protective efficacy of Ty21a against NTS. Materials and methods 35 volunteers receiving Ty21a vaccine and five patients with enteric fever were investigated with ELISPOT for circulating Plasmablasts secreting antibodies reactive with Salmonella Typhi and six different NTS serotypes. These Plasmablasts were also analysed for homing receptor expressions. Results In all vaccinees and patients, a strong gut-directed cross-reactive Plasmablast response was found against serotypes sharing the two O-antigens with Salmonella Typhi (O-9,12) (in vaccinees, mean: 95%CI 268: 228–508 and 363: 234–493 Plasmablasts/10 6 PBMC against Salmonella Typhi and Enteritidis). Responses against strains sharing one O-antigen (O-12) were weaker (222: 105–338 against Salmonella Typhimurium), while no significant reactivity was detected against strains without typhoidal O-antigens. Conclusions Intestinal antibodies against O-antigens protect against NTS in animal experiments. Ty21a was found to elicit intestinal immune responses cross-reactive with NTS strains sharing O-antigens with Ty21a. These include the most common NTS, Salmonella Enteritidis and Typhimurium. The data suggest that Ty21a may have cross-protective efficacy against numerous NTS strains.
Rafi Ahmed - One of the best experts on this subject based on the ideXlab platform.
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b cell responses during secondary dengue virus infection are dominated by highly cross reactive memory derived Plasmablasts
Journal of Virology, 2016Co-Authors: Lalita Priyamvada, Nattawat Onlamoon, Kovit Pattanapanyasat, Yevgeniy Kovalenkov, Alice Cho, Nai Ying Zheng, Min Huang, Kulkanya Chokephaibulkit, Nasikarn Angkasekwinai, Rafi AhmedAbstract:ABSTRACT Dengue virus (DENV) infection results in the production of both type-specific and cross-neutralizing antibodies. While immunity to the infecting serotype is long-lived, heterotypic immunity wanes a few months after infection. Epidemiological studies link secondary heterotypic infections with more severe symptoms, and cross-reactive, poorly neutralizing antibodies have been implicated in this increased disease severity. To understand the cellular and functional properties of the acute dengue virus B cell response and its role in protection and immunopathology, we characterized the Plasmablast response in four secondary DENV type 2 (DENV2) patients. Dengue Plasmablasts had high degrees of somatic hypermutation, with a clear preference for replacement mutations. Clonal expansions were also present in each donor, strongly supporting a memory origin for these acutely induced cells. We generated 53 monoclonal antibodies (MAbs) from sorted patient Plasmablasts and found that DENV-reactive MAbs were largely envelope specific and cross neutralizing. Many more MAbs neutralized DENV than reacted to envelope protein, emphasizing the significance of virion-dependent B cell epitopes and the limitations of envelope protein-based antibody screening. A majority of DENV-reactive MAbs, irrespective of neutralization potency, enhanced infection by antibody-dependent enhancement (ADE). Interestingly, even though DENV2 was the infecting serotype in all four patients, several MAbs from two patients neutralized DENV1 more potently than DENV2. Further, half of all type-specific neutralizing MAbs were also DENV1 biased in binding. Taken together, these findings are reminiscent of original antigenic sin (OAS), given that the patients had prior dengue virus exposures. These data describe the ongoing B cell response in secondary patients and may further our understanding of the impact of antibodies in dengue virus pathogenesis. IMPORTANCE In addition to their role in protection, antibody responses have been hypothesized to contribute to the pathology of dengue. Recent studies characterizing memory B cell (MBC)-derived MAbs have provided valuable insight into the targets and functions of B cell responses generated after DENV exposure. However, in the case of secondary infections, such MBC-based approaches fail to distinguish acutely induced cells from the preexisting MBC pool. Our characterization of Plasmablasts and Plasmablast-derived MAbs provides a focused analysis of B cell responses activated during ongoing infection. Additionally, our studies provide evidence of OAS in the acute-phase dengue virus immune response, providing a basis for future work examining the impact of OAS phenotype antibodies on protective immunity and disease severity in secondary infections.
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frequency and phenotype of human immunodeficiency virus envelope specific b cells from patients with broadly cross neutralizing antibodies
Journal of Virology, 2009Co-Authors: Nicole A Doriarose, Jens Wrammert, Rachel M Klein, Maura Manion, Sijy Odell, Adhuna Phogat, Bimal K Chakrabarti, Claire W Hallahan, Stephen A Migueles, Rafi AhmedAbstract:Induction of broadly cross-reactive neutralizing antibodies (NAb) is an important goal for a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. Some HIV-infected patients make a NAb response that reacts with diverse strains of HIV-1, but most candidate vaccines have induced NAb only against a subset of highly sensitive isolates. To better understand the nature of broad NAb responses that arise during natural infection, we screened patients for sera able to neutralize diverse HIV strains and explored the frequency and phenotype of their peripheral Envelope-specific B cells. We screened 113 HIV-infected patients of various clinical statuses for the prevalence of broad NAb. Sera able to neutralize at least four of five viral isolates were found in over one-third of progressors and slow progressors, but much less frequently in aviremic long-term nonprogressors. Most Env-specific antibody-secreting B cells were CD27hi CD38hi Plasmablasts, and the total Plasmablast frequency was higher in HIV-infected patients than in uninfected donors. We found that 0.0031% of B cells and 0.047% of Plasmablasts secreted Env-specific immunoglobulin G (IgG) in an enzyme-linked immunospot (ELISPOT) assay. We developed a novel staining protocol to label HIV-specific B cells with Env gp140 protein. A total of 0.09% of B cells were found to be Env-specific by this method, a frequency far higher than that indicated by ELISPOT assay. gp140-labeled B cells were predominantly CD27+ and surface IgG+. These data describe the breadth and titer of serum NAb and the frequency and phenotype of HIV-specific B cells in a cohort of patients with broad cross-neutralizing antibody responses that are potential goals for vaccines for HIV.