scholarly journals Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Kristen A. Clarkson ◽  
Robert W. Frenck ◽  
Michelle Dickey ◽  
Akamol E. Suvarnapunya ◽  
Lakshmi Chandrasekaran ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Antibody Responses ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Serum ◽  
Serum Iga ◽  
Risk Of Disease ◽  
Reduced Risk

ABSTRACT Shigella is a major cause of moderate to severe diarrhea largely affecting children (<5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or functional antibody responses postchallenge; however, higher lipopolysaccharide (LPS)-specific serum IgA- and IgA-secreting memory B cell responses were associated with a reduced risk of disease postchallenge. This study provides unique insights into the immune responses pre- and postinfection with S. sonnei 53G in a CHIM, which could help guide the rational design of future vaccines to induce protective immune responses more analogous to those triggered by infection. IMPORTANCE Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.

scholarly journals Antigen-Specific Memory B-Cell Responses in Bangladeshi Adults after One- or Two-Dose Oral Killed Cholera Vaccination and Comparison with Responses in Patients with Naturally Acquired Cholera

2011 ◽  
Vol 18 (5) ◽  
pp. 844-850 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
M. Asrafuzzaman Riyadh ◽  
Kaniz Fatema ◽  
Mohammad Arif Rahman ◽  
Nayeema Akhtar ◽  
...  
Keyword(s):  
B Cell ◽  
Acute Stage ◽  
Cholera Toxin B Subunit ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Memory ◽  
Dose Oral ◽  
B Cell Responses ◽  
Cholera Vaccination

ABSTRACTThe mediators of protective immunity against cholera are currently unknown, but memory B-cell responses may play a central role in facilitating long-term and anamnestic responses againstVibrio cholerae, the cause of cholera. We compared memory B-cell responses in adults with natural cholera in Bangladesh (n= 70) to responses in Bangladeshi adults after one-dose (n= 30) or two-dose (n= 30) administration of an oral killed cholera vaccine, WC-rBS (Dukoral; Crucell), assessing the responses at the acute stage of disease or prevaccination and then on days 3, 30, 90, 180, 270, and 360. Individuals with natural cholera developed prominent vibriocidal and plasma anti-cholera toxin B subunit (CtxB) and lipopolysaccharide (LPS) IgG and IgA responses, but these responses returned to baseline by 1 year of follow-up. Vaccinees developed plasma anti-CtxB and anti-LPS IgG and IgA responses that were generally comparable to those in individuals recovering from natural disease, but vibriocidal responses were lower in vaccinees than in infected patients. Individuals recovering from natural disease developed memory B-cell IgG and IgA anti-CtxB and anti-LPS responses by day 30, and these responses were detectable through at least days 180 to 360. In contrast, we detected no IgA or IgG memory B-cell responses to LPS in vaccinees; anti-CtxB IgA responses were only detectable on day 30, and anti-CtxB IgG responses were detectable until days 90 to 180, compared to days 270 to 360 in patients. These findings may explain in part the relatively short-term protection afforded by oral cholera vaccination compared to natural disease.

scholarly journals Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection

2012 ◽  
Vol 20 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
Mohammad Arifuzzaman ◽  
Shaikh Meshbahuddin Ahmad ◽  
M. Ismail Hosen ◽  
Mohammad Arif Rahman ◽  
...  
Keyword(s):  
B Cell ◽  
Vibrio Cholerae ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Memory ◽  
Iga Antibodies ◽  
Specific Igg ◽  
B Cell Responses

ABSTRACTThe avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) andVibrio choleraeO1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n= 30), as well as vaccinees (n= 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P< 0.05; Spearman'sρ= 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses toVibrio choleraeO1 antigens.

scholarly journals Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine

2007 ◽  
Vol 15 (2) ◽  
pp. 182-193 ◽  
Author(s):  
Elizabeth A. Clutterbuck ◽  
Sarah Oh ◽  
Mainga Hamaluba ◽  
Sharon Westcar ◽  
Peter C. L. Beverley ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Memory B Cell ◽  
Cell Responses ◽  
Specific Memory

ABSTRACT Glycoconjugate vaccines have dramatically reduced the incidence of encapsulated bacterial diseases in toddlers under 2 years of age, but vaccine-induced antibody levels in this age group wane rapidly. We immunized adults and 12-month-old toddlers with heptavalent pneumococcal conjugate vaccine to determine differences in B-cell and antibody responses. The adults and 12-month-old toddlers received a pneumococcal conjugate vaccine. The toddlers received a second dose at 14 months of age. The frequencies of diphtheria toxoid and serotype 4, 14, and 23F polysaccharide-specific plasma cells and memory B cells were determined by enzyme-linked immunospot assay. The toddlers had no preexisting polysaccharide-specific memory B cells or serum immunoglobulin G (IgG) antibody but had good diphtheria toxoid-specific memory responses. The frequencies of plasma cells and memory B cells increased by day 7 (P < 0.0001) in the adults and the toddlers following a single dose of conjugate, but the polysaccharide responses were significantly lower in the toddlers than in the adults (P = 0.009 to <0.001). IgM dominated the toddler antibody responses, and class switching to the IgG was serotype dependent. A second dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults.

scholarly journals Memory T-Cell Responses to Vibrio cholerae O1 Infection

2009 ◽  
Vol 77 (11) ◽  
pp. 5090-5096 ◽  
Author(s):  
Ana A. Weil ◽  
Mohammad Arifuzzaman ◽  
Taufiqur R. Bhuiyan ◽  
Regina C. LaRocque ◽  
Aaron M. Harris ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Memory B Cell ◽  
Memory T Cell ◽  
Cell Responses ◽  
B Cell Responses

ABSTRACTVibrio choleraeO1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses toV. choleraeinfection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severeV. choleraeinfection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses usingV. choleraeantigens, including the toxin-coregulated pilus (TcpA), aV. choleraemembrane preparation, and theV. choleraecytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses toV. choleraeantigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to otherV. choleraeantigens.

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.

scholarly journals The presence of circulating antibody secreting cells and long-lived memory B cell responses to reticulocyte binding protein 1a in Plasmodium vivax patients

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Piyawan Kochayoo ◽  
Pattarawan Sanguansuttikul ◽  
Pongsakorn Thawornpan ◽  
Kittikorn Wangriatisak ◽  
John H. Adams ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Blood Stage ◽  
Memory B Cell ◽  
Cell Responses ◽  
Antibody Titers ◽  
B Cell Responses

Abstract Background Development of an effective vaccine against blood-stage malaria requires the induction of long-term immune responses. Plasmodium vivax Reticulocyte Binding Protein 1a (PvRBP1a) is a blood-stage parasite antigen which is associated with invasion of red blood cells and induces antibody responses. Thus, PvRBP1a is considered as a target for design of a blood-stage vaccine against vivax malaria. Methods Both cross-sectional and cohort studies were used to explore the development and persistence of long-lived antibody and memory B cell responses to PvRBP1a in individuals who lived in an area of low malaria endemicity. Antibody titers and frequency of memory B cells specific to PvRBP1a were measured during infection and following recovery for up to 12 months. Results IgG antibody responses against PvRBP1a were prevalent during acute vivax malaria, predominantly IgG1 subclass responses. High responders to PvRBP1a had persistent antibody responses for at least 12-month post-infection. Further analysis of high responder found a direct relation between antibody titers and frequency of activated and atypical memory B cells. Furthermore, circulating antibody secreting cells and memory B cells specific to PvRBP1a were generated during infection. The PvRBP1a-specific memory B cells were maintained for up to 3-year post-infection, indicating the ability of PvRBP1a to induce long-term humoral immunity. Conclusion The study revealed an ability of PvRBP1a protein to induce the generation and maintenance of antibody and memory B cell responses. Therefore, PvRBP1a could be considered as a vaccine candidate against the blood-stage of P. vivax.

scholarly journals Cross-reactive serum and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

2020 ◽  
Author(s):  
Ge Song ◽  
Wan-ting He ◽  
Sean Callaghan ◽  
Fabio Anzanello ◽  
Deli Huang ◽  
...  
Keyword(s):  
B Cell ◽  
Natural Infection ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Memory B Cell ◽  
Cell Responses ◽  
Weak Evidence ◽  
Coronavirus Infection ◽  
B Cell Responses

AbstractPre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, either induced in natural infection or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. We compared serum antibody and memory B cell responses to coronavirus spike (S) proteins from pre-pandemic and SARS-CoV-2 convalescent donors using a series of binding and functional assays. We found weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we found stronger evidence of pre-existing cross-reactive memory B cells that were activated on SARS-CoV-2 infection. Monoclonal antibodies (mAbs) isolated from the donors showed varying degrees of cross-reactivity with betacoronaviruses, including SARS and endemic coronaviruses. None of the cross-reactive mAbs were neutralizing except for one that targeted the S2 subunit of the S protein. The results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2.

scholarly journals Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination

2021 ◽  
Author(s):  
Rishi R. Goel ◽  
Sokratis A. Apostolidis ◽  
Mark M. Painter ◽  
Divij Mathew ◽  
Ajinkya Pattekar ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Antibody Responses ◽  
Short Term ◽  
Memory B Cell ◽  
Cell Responses ◽  
Specific Memory ◽  
B Cell Responses ◽  
Antibody Levels

ABSTRACTNovel mRNA vaccines for SARS-CoV2 have been authorized for emergency use and are currently being administered to millions of individuals worldwide. Despite their efficacy in clinical trials, there is limited data on vaccine-induced immune responses in individuals with a prior SARS-CoV2 infection compared to SARS-CoV2 naïve subjects. Moreover, how mRNA vaccines impact the development of antibodies as well as memory B cells in COVID-19 experienced versus COVID-19 naïve subjects remains poorly understood. In this study, we evaluated antibody responses and antigen-specific memory B cell responses over time in 33 SARS-CoV2 naïve and 11 SARS-CoV2 recovered subjects. mRNA vaccination induced significant antibody and memory B cell responses against full-length SARS-CoV2 spike protein and the spike receptor binding domain (RBD). SARS-CoV2 naïve individuals benefitted from both doses of mRNA vaccine with additional increases in antibodies and memory B cells following booster immunization. In contrast, SARS-CoV2 recovered individuals had a significant immune response after the first dose with no increase in circulating antibodies or antigen-specific memory B cells after the second dose. Moreover, the magnitude of the memory B cell response induced by vaccination was lower in older individuals, revealing an age-dependence to mRNA vaccine-induced B cell memory. Side effects also tended to associate with post-boost antibody levels, but not with post-boost memory B cells, suggesting that side effect severity may be a surrogate of short-term antibody responses. The frequency of pre-vaccine antigen-specific memory B cells in SARS-CoV2 recovered individuals strongly correlated with post-vaccine antibody levels, supporting a key role for memory B cells in humoral recall responses to SARS-CoV2. This observation may have relevance for future booster vaccines and for responses to viral variants that partially escape pre-existing antibodies and require new humoral responses to be generated from memory B cells. Finally, post-boost antibody levels were not correlated with post-boost memory responses in SARS-CoV2 naïve individuals, indicating that short-term antibody levels and memory B cells are complementary immunological endpoints that should be examined in tandem when evaluating vaccine response. Together, our data provide evidence of both serological response and immunological memory following mRNA vaccination that is distinct based on prior SARS-CoV2 exposure. These findings may inform vaccine distribution in a resource-limited setting.Abstract Figure

scholarly journals Two Vaccines forStaphylococcus aureusInduce a B-Cell-Mediated Immune Response

mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Christopher D. Dupont ◽  
Ingrid L. Scully ◽  
Ross M. Zimnisky ◽  
Brinda Monian ◽  
Christina P. Rossitto ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Severe Disease ◽  
Antibody Responses ◽  
Protein Antigens ◽  
Content Type ◽  
The Impact

ABSTRACTStaphylococcus aureuscauses severe disease in humans for which no licensed vaccine exists. A novelS. aureusvaccine (SA4Ag) is in development, targeting the capsular polysaccharides (CPs) and two virulence-associated surface proteins. Vaccine-elicited antibody responses to CPs are efficacious against serious infection by other encapsulated bacteria. Studies of naturalS. aureusinfection have also shown a role for TH17 and/or TH1 responses in protection. Single-antigen vaccines, including CPs, have not been effective againstS. aureus; a multiantigen vaccine approach is likely required. However, the impact of addition of protein antigens on the immune response to CPs has not been studied. Here, the immune response induced by a bivalent CP conjugate vaccine (to model the established mechanism of action of vaccine-induced protection against Gram-positive pathogens) was compared to the response induced by SA4Ag, which contains both CP conjugates and protein antigens, in cynomolgus macaques. Microengraving, flow cytometry, opsonophagocytic assays, and Luminex technology were used to analyze the B-cell, T-cell, functional antibody, and innate immune responses. Both the bivalent CP vaccine and SA4Ag induced cytokine production from naive cells and antigen-specific memory B-cell and functional antibody responses. Increases in levels of circulating, activated T cells were not apparent following vaccination, nor was a TH17 or TH1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (TFH) cells to lymph nodes. Collectively, these data suggest that the response to SA4Ag is primarily mediated by B cells and antibodies that abrogate importantS. aureusvirulence mechanisms.IMPORTANCEStaphylococcus aureuscauses severe disease in humans for which no licensed vaccine exists. A novel vaccine is in development that targets multiple elements of the bacteria since single-component vaccines have not shown efficacy to date. How these multiple components alter the immune response raised by the vaccine is not well studied. We found that the addition of two protein components did not alter substantially the antibody responses raised with respect to function or mobilization of B cells. There was also not a substantial change in the activity of T cells, another part of the adaptive response. This study showed that protection by this vaccine may be mediated primarily by antibody protection.

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