scholarly journals A Systems Biology Approach Identifies B Cell Maturation Antigen (BCMA) as a Biomarker Reflecting Oral Vaccine Induced IgA Antibody Responses in Humans

2021 ◽  
Vol 12 ◽  
Author(s):  
Lynda Mottram ◽  
Anna Lundgren ◽  
Ann-Mari Svennerholm ◽  
Susannah Leach

Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.

2021 ◽  
Vol 12 ◽  
pp. 204062072198958
Author(s):  
Larysa Sanchez ◽  
Alexandra Dardac ◽  
Deepu Madduri ◽  
Shambavi Richard ◽  
Joshua Richter

Outcomes of patients with multiple myeloma (MM) who become refractory to standard therapies are particularly poor and novel agents are greatly needed to improve outcomes in such patients. B-cell maturation antigen (BCMA) has become an important therapeutic target in MM with three modalities of treatment in development including antibody–drug conjugates (ADCs), bispecific T-cell engagers (BITEs), and chimeric antigen receptor (CAR) T-cell therapies. Early clinical trials of anti-BCMA immunotherapeutics have demonstrated extremely promising results in heavily pretreated patients with relapsed/refractory MM (RRMM). Recently, belantamab mafodotin was the first anti-BCMA therapy to obtain approval in relapsed/refractory MM. This review summarizes the most updated efficacy and safety data from clinical studies of BCMA-targeted therapies with a focus on ADCs and BITEs. Additionally, important differences among the BCMA-targeted treatment modalities and their clinical implications are discussed.


2010 ◽  
Vol 37 (8) ◽  
pp. 3747-3755 ◽  
Author(s):  
Shaoli Deng ◽  
Tao Yuan ◽  
Xiaoxing Cheng ◽  
Rui Jian ◽  
Jing Jiang

2013 ◽  
Vol 19 (8) ◽  
pp. 2048-2060 ◽  
Author(s):  
Robert O. Carpenter ◽  
Moses O. Evbuomwan ◽  
Stefania Pittaluga ◽  
Jeremy J. Rose ◽  
Mark Raffeld ◽  
...  

2016 ◽  
Vol 174 (6) ◽  
pp. 911-922 ◽  
Author(s):  
Lydia Lee ◽  
Danton Bounds ◽  
Jennifer Paterson ◽  
Gaelle Herledan ◽  
Katherine Sully ◽  
...  

2019 ◽  
Vol 10 ◽  
Author(s):  
Marijke Timmers ◽  
Gils Roex ◽  
Yuedi Wang ◽  
Diana Campillo-Davo ◽  
Viggo F. I. Van Tendeloo ◽  
...  

2019 ◽  
Vol 14 (5) ◽  
pp. 551-561 ◽  
Author(s):  
Kyle A. Udd ◽  
Sean Bujarski ◽  
Eric Wirtschafter ◽  
Tanya M. Spektor ◽  
Matthew Ghermezi ◽  
...  

2018 ◽  
Author(s):  
Henia Dar ◽  
Daniel Henderson ◽  
Zinkal Padalia ◽  
Ashley Porras ◽  
Dakai Mu ◽  
...  

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