Genomic correlates of variability in immune response to an oral cholera vaccine

Majumder, Partha P.; Sarkar-Roy, Neeta; Staats, Herman F.; Ramamurthy, T.; Maiti, Sujit; Chowdhury, Goutam; Whisnant, Carol C.; Narayanasamy, K; Wagener, Diane K.

doi:10.1038/ejhg.2012.278

Cited by 9 publications

(10 citation statements)

References 57 publications

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“…A single cell layer of the mucosal epithelium essentially regulates intestinal homeostasis [30]. This physical barrier is a prominent part of the innate immune system with damage-healing and infection-limiting properties.…”

Section: Discussionmentioning

confidence: 99%

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Genomics of immune response to typhoid and cholera vaccines

Majumder

2015

Phil. Trans. R. Soc. B

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One contribution of 15 to a discussion meeting issue 'Biological challenges to effective vaccines in the developing world'. Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.

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Section: Discussionmentioning

confidence: 99%

“…0.05). We tested for existence of cryptic relatedness and population stratification using Eigenstrat [29]; no evidence was detected as all individuals formed a single cluster in the scatterplot of the first three principal components [30] ( figure 1). …”

Section: (B) Genomic Association Discovery and Validationmentioning

confidence: 99%

Genomics of immune response to typhoid and cholera vaccines

Majumder

2015

Phil. Trans. R. Soc. B

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“…These genes with additional protein interactions are shown in this figure. Marco, TNFAIP3, and CXCL12are associated with the categories of epithelial barrier integrity, scavenger receptor family, intestinal homeostasis, and leukocyte attractant/recruitment [ 2 , 7 ]…”

Section: Figurementioning

confidence: 99%

Cholera host response gene networks: preliminary studies

Shapshak¹,

Somboonwit²,

Cao³

et al. 2017

Bioinformation

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Gene network analysis was performed based on published literature describing genes that are possibly interconnected with cholera vaccine responses in vitro in cell culture and in vivo in human patient punch biopsies as well as DNA extracted from blood. These studies produced divergent results. The differences should be replicated and studied further. Included in such studies, patient ethnicities, states of stress, nutrition, and health, as well as the precise characteristics of the various cholera vaccines and modes of delivery need to be considered as well.

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“…Gene-environment interplay in immune phenotypes has been extensively studied using steady-state cellular immune profiles (1–3), functional immune responses (2,4–8), post-vaccination responses (9,10) and V,D and J usage biases in naïve and memory T and B cell compartments (11). Some of these studies have identified genomic correlates associated with specific steady-state immune phenotypes (2) and vaccine responses (12). However, there are conflicting findings regarding the relative importance of genetic versus environmental factors in regulation of immune phenotype (1,2,13,14), warranting further investigations at the population-level in humans and mechanistic studies in mice on regulation of individual immune phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Cell-intrinsic genetic regulation of peripheral memory-phenotype T cell frequencies

Chawla

Kanodia

Mukherjee

et al. 2018

Preprint

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4344 Gene-environment interplay in immune phenotypes has been extensively studied using steady-45 state cellular immune profiles (1-3), functional immune responses (2,(4)(5)(6)(7)(8), post-vaccination 46 responses (9,10) and V,D and J usage biases in naïve and memory T and B cell compartments 47 (11). Some of these studies have identified genomic correlates associated with specific steady-48 state immune phenotypes (2) and vaccine responses (12). However, there are conflicting findings 49 regarding the relative importance of genetic versus environmental factors in regulation of 50 immune phenotype (1,2,13,14), warranting further investigations at the population-level in 51 humans and mechanistic studies in mice on regulation of individual immune phenotypes. 52 53 Memory subsets in T and B lymphocytes are immune populations that are generated in response 54 to past immunogen exposure. Immunological memory, providing long-term persistence of 55 antigen-experienced cells contributing to rapid and robust responses following re-exposure (15), 56 is likely to have evolved in an ecosystem where environmental challenges including repeated 57 infections would be the norm (16) and the persistence of long-lasting antigen-specific cells 58 generated during immune responses would confer survival advantage (17). However, it is 59 possible that larger memory lymphocyte pool sizes may carry costs such as restriction of space 60 for the more repertoire-diverse naive T cell compartment (18), attrition of pre-existing memory 61 (19), and other bioenergetic costs (20). Such selection may well result in 'optimum' sizes of 62 memory lymphocyte pools (21), and these pool sizes could show population diversity, depending 63 on the diversity of pathogens in the ecosystem and their exposure rates (22). Diversity in pool 64 sizes of memory lymphocytes in a population could thus be determined by a combination of 65 genetic variability and diversity of environmental exposures. 66 4 67 A number of mechanisms can be envisaged regulating the pool size of the memory T cell 68 compartment, including cumulative life-time antigen-exposure and re-exposure, antigenic 69 persistence, degree of expansion, cell survival, attrition and niche-space availability (21,23-26). 70 Immune cells occupy a limited niche space in lymphoid organs (27) or in the periphery (28). This 71 niche size could be a function of size and/or structure of supporting lymphoid tissue architecture 72 (29), along with intrinsic properties of cells occupying the niche. Similar determinants could 73 affect steady state levels of transient cell populations such as immediate-effector T cells (30) and 74 plasmablasts, but their steady state levels would be expected to fluctuate more with short-term 75 environmental changes. 7677 On this background, we have explored the possibility of gene-environment interplay affecting the 78 steady state pool sizes of lymphocytes post-activation. We have used peripheral blood leucocyte 79 immunophenotyping in serial bleeds from healthy young adult hum...

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Genomic correlates of variability in immune response to an oral cholera vaccine

Cited by 9 publications

References 57 publications

Genomics of immune response to typhoid and cholera vaccines

Genomics of immune response to typhoid and cholera vaccines

Cholera host response gene networks: preliminary studies

Cell-intrinsic genetic regulation of peripheral memory-phenotype T cell frequencies

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