scholarly journals 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

2011 ◽  
Vol 18 (8) ◽  
pp. 1317-1325 ◽  
Author(s):  
Daniel T. Leung ◽  
Mohammad Arif Rahman ◽  
M. Mohasin ◽  
M. Asrafuzzaman Riyadh ◽  
Sweta M. Patel ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
B Cell ◽  
Protective Efficacy ◽  
Age Groups ◽  
Older Children ◽  
Secreting Cell ◽  
Content Type ◽  
Antibody Secreting Cell ◽  
Plasma Antibody

ABSTRACTChildren 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 toVibrio choleraeantigens, 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 toV. choleraelipopolysaccharide 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 againstV. choleraeO1, suggesting that under an optimal vaccination strategy, young children could achieve protective efficacy comparable to that induced in adults.

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 Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
M. Hasanul Kaisar ◽  
Mohammed Saruar Bhuiyan ◽  
Aklima Akter ◽  
Danial Saleem ◽  
Anita S. Iyer ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Natural Infection ◽  
Intestinal Epithelial ◽  
Older Children ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Age Related

ABSTRACT Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent cholera, but currently available vaccines provide only 3 to 5 years of protection. Understanding immune responses to cholera antigens in naturally infected individuals may elucidate which of these are key to longer-term protection seen following infection. We recently identified Vibrio cholerae O1 sialidase, a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells, as immunogenic following infection in two recent high-throughput screens. Here, we present systemic, mucosal, and memory immune responses to sialidase in cholera index cases and evaluated whether systemic responses to sialidase correlated with protection using a cohort of household contacts. Overall, we found age-related differences in antisialidase immune response following cholera. Adults developed significant plasma anti-sialidase IgA, IgG, and IgM responses following infection, whereas older children (≥5 years) developed both IgG and IgM responses, and younger children only developed IgM responses. Neither older children nor younger children had a rise in IgA responses over the convalescent phase of infection (day 7/day 30). On evaluation of mucosal responses and memory B-cell responses to sialidase, we found adults developed IgA antibody-secreting cell (ASC) and memory B-cell responses. Finally, in household contacts, the presence of serum anti-sialidase IgA, IgG, and IgM antibodies at enrollment was associated with a decrease in the risk of subsequent infection. These data show cholera patients develop age-related immune responses against sialidase and suggest that immune responses that target sialidase may contribute to protective immunity against cholera. IMPORTANCE Cholera infection can result in severe dehydration that may lead to death within a short period of time if not treated immediately. Vaccination is an important strategy to prevent the disease. Oral cholera vaccines provide 3 to 5 years of protection, with 60% protective efficacy, while natural infection provides longer-term protection than vaccination. Understanding the immune responses after natural infection is important to better understand immune responses to antigens that mediate longer-term protection. Sialidase is a neuraminidase that facilitates binding of cholera toxin to intestinal epithelial cells. We show here that patients with cholera develop systemic, mucosal, and memory B-cell immune responses to the sialidase antigen of Vibrio cholerae O1 and that plasma responses targeting this antigen correlate with protection.

scholarly journals O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh

2016 ◽  
Vol 23 (5) ◽  
pp. 427-435 ◽  
Author(s):  
Amena Aktar ◽  
M. Arifur Rahman ◽  
Sadia Afrin ◽  
M. Omar Faruk ◽  
Taher Uddin ◽  
...  
Keyword(s):  
Young Children ◽  
B Cell ◽  
Older Children ◽  
Memory B Cell ◽  
Content Type ◽  
Age Cohorts ◽  
Cell Responses ◽  
Specific Memory ◽  
Specific Polysaccharide ◽  
B Cell Responses

ABSTRACTCholera caused byVibrio choleraeO1 confers at least 3 to 10 years of protection against subsequent disease regardless of age, despite a relatively rapid fall in antibody levels in peripheral blood, suggesting that memory B cell responses may play an important role in protection. TheV. choleraeO1-specific polysaccharide (OSP) component of lipopolysaccharide (LPS) is responsible for serogroup specificity, and it is unclear if young children are capable of developing memory B cell responses against OSP, a T cell-independent antigen, following cholera. To address this, we assessed OSP-specific memory B cell responses in young children (2 to 5 years,n= 11), older children (6 to 17 years,n= 21), and adults (18 to 55 years,n= 28) with cholera caused byV. choleraeO1 in Dhaka, Bangladesh. We also assessed memory B cell responses against LPS and vibriocidal responses, and plasma antibody responses against OSP, LPS, and cholera toxin B subunit (CtxB; a T cell-dependent antigen) on days 2 and 7, as well as days 30, 90, and 180 after convalescence. In all age cohorts, vibriocidal responses and plasma OSP, LPS, and CtxB-specific responses peaked on day 7 and fell toward baseline over the follow-up period. In comparison, we were able to detect OSP memory B cell responses in all age cohorts of patients with detectable responses over baseline for 90 to 180 days. Our results suggest that OSP-specific memory B cell responses can occur following cholera, even in the youngest children, and may explain in part the age-independent induction of long-term immunity following naturally acquired disease.

RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum

2017 ◽  
Vol 1 (6) ◽  
pp. 533-537
Author(s):  
Lorenz von Seidlein ◽  
Borimas Hanboonkunupakarn ◽  
Podjanee Jittmala ◽  
Sasithon Pukrittayakamee
Keyword(s):  
Protective Efficacy ◽  
Age Groups ◽  
Sub Saharan Africa ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Older Children ◽  
Pivotal Phase ◽  
Malaria Epidemiology ◽  
Maximum Benefit ◽  
Sub Saharan

RTS,S/AS01 is the most advanced vaccine to prevent malaria. It is safe and moderately effective. A large pivotal phase III trial in over 15 000 young children in sub-Saharan Africa completed in 2014 showed that the vaccine could protect around one-third of children (aged 5–17 months) and one-fourth of infants (aged 6–12 weeks) from uncomplicated falciparum malaria. The European Medicines Agency approved licensing and programmatic roll-out of the RTSS vaccine in malaria endemic countries in sub-Saharan Africa. WHO is planning further studies in a large Malaria Vaccine Implementation Programme, in more than 400 000 young African children. With the changing malaria epidemiology in Africa resulting in older children at risk, alternative modes of employment are under evaluation, for example the use of RTS,S/AS01 in older children as part of seasonal malaria prophylaxis. Another strategy is combining mass drug administrations with mass vaccine campaigns for all age groups in regional malaria elimination campaigns. A phase II trial is ongoing to evaluate the safety and immunogenicity of the RTSS in combination with antimalarial drugs in Thailand. Such novel approaches aim to extract the maximum benefit from the well-documented, short-lasting protective efficacy of RTS,S/AS01.

scholarly journals 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

2003 ◽  
Vol 71 (8) ◽  
pp. 4808-4814 ◽  
Author(s):  
Firdausi Qadri ◽  
Edward T. Ryan ◽  
A. S. G. Faruque ◽  
Firoz Ahmed ◽  
Ashraful Islam Khan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immunoglobulin A ◽  
Peripheral Circulation ◽  
Secreting Cell ◽  
Antibody Secreting Cell ◽  
Immunological Responses ◽  
B Subunit ◽  
Mucosal Infection ◽  
Circulating Lymphocytes

ABSTRACT 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.

scholarly journals 1105. Vibriocidal Titer Variation and Likelihood of Protection in Children Compared With Adults in a Cholera Endemic Area

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S331-S331
Author(s):  
Alaina Ritter ◽  
Fahima Chowdhury ◽  
Rachel Becker ◽  
Taufiq Bhuiyan ◽  
Ashraful Khan ◽  
...  
Keyword(s):  
Young Children ◽  
Vaccine Development ◽  
Massachusetts General Hospital ◽  
Age Groups ◽  
Older Children ◽  
Baseline Serum ◽  
Household Contacts ◽  
Antibody Titers ◽  
Training Grant

Abstract Background Vibrio cholerae, the causative agent of cholera, is responsible for significant morbidity and mortality worldwide. Children less than 5 years old have the highest disease burden of cholera in endemic areas. While children develop serum vibriocidal antibody responses to cholera vaccines, they derive less protection from vaccination compared with adults. The aim of our study was to determine whether the vibriocidal immune responses to V. cholerae infection are equally accurate as markers of protection in all age groups. Methods Cholera patients and their household contacts, who are known to be at high risk of V. cholerae infection, were enrolled between 2001 and 2017 in Dhaka, Bangladesh. Baseline vibriocidal titers were measured at the time of enrollment of household contacts, and participants were followed prospectively for development of V. cholerae infection. Results We studied 50 contacts < 5 years old (“young children”), 228 contacts 5–16 years old (“older children”), and 548 contacts > 16 years old (“adults”). The baseline serum vibriocidal titer was higher in contacts who remained uninfected from all age groups than in contacts who developed cholera during the follow-up period (young children: P = 0.0092; older children: P = 0.0003, adults: P = 0.0012). Conclusion We found that higher vibriocidal antibody titers were associated with protection against V. cholerae infection across all three age categories. These findings may help increase our understanding of the protective immune response against V. cholerae infection and have importance for future vaccine development strategies. Acknowledgments: This research was supported by Massachusetts General Hospital training grant T32AI007061. Disclosures All authors: No reported disclosures.

scholarly journals Immunological Responses to the Relapsing Fever SpirocheteBorrelia turicataein Infected Rhesus Macaques: Implications for Pathogenesis and Diagnosis

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Monica E. Embers ◽  
Aparna Krishnavajhala ◽  
Brittany A. Armstrong ◽  
Michael W. Curtis ◽  
Bapi Pahar ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Rhesus Macaques ◽  
Surface Proteins ◽  
Vaccine Antigen ◽  
Global Public Health ◽  
Relapsing Fever ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Content Type

ABSTRACTThe global public health impact of relapsing fever (RF) spirochetosis is significant, since the pathogens exist on five of seven continents. The hallmark sign of infection is episodic fever and the greatest threat is to the unborn. With the goal of better understanding the specificity of B-cell responses and the role of immune responses in pathogenicity, we infected rhesus macaques withBorrelia turicatae(a new world RF spirochete species) by tick bite and monitored the immune responses generated in response to the pathogen. Specifically, we evaluated inflammatory mediator induction by the pathogen, host antibody responses to specific antigens, and peripheral lymphocyte population dynamics. Our results indicate thatB. turicataeelicits from peripheral blood cells key inflammatory response mediators (interleukin-1β and tumor necrosis factor alpha), which are associated with preterm abortion. Moreover, a global decline in peripheral B-cell populations was observed in all animals at 14 days postinfection. Serological responses were also evaluated to assess the antigenicity of three surface proteins: BipA, BrpA, and Bta112. Interestingly, a distinction was observed between antibodies generated in nonhuman primates and mice. Our results provide support for the nonhuman primate model not only in studies of prenatal pathogenesis but also for diagnostic and vaccine antigen identification and testing.

scholarly journals EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production

2017 ◽  
Vol 200 (3) ◽  
pp. 1039-1052 ◽  
Author(s):  
Muyao Guo ◽  
Madeline J. Price ◽  
Dillon G. Patterson ◽  
Benjamin G. Barwick ◽  
Robert R. Haines ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Production ◽  
Cell Metabolism ◽  
Transcriptional Program ◽  
Secreting Cell ◽  
Antibody Secreting Cell
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