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Genomic determinants of antibody response to a typhoid vaccine in Indian recipients

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Abstract

Typhoid is endemic in India and has high global incidence. There were large outbreaks of typhoid in India between 1990 and 2018. Available typhoid vaccines induce variable levels of protective antibodies among recipients; thus, there is variability in response to the vaccine. Interindividual genomic differences is hypothesized to be a determinant of the variability in response. We studied the antibody response of ~1000 recipients of the Vi-polysaccharide typhoid vaccine from Kolkata, India, who showed considerable variability of antibody response, i.e., anti-Vi-polysaccharide antibody level 28 days postvaccination relative to prevaccination. For each vaccinee, whole-genome genotyping was performed using the Infinium Global Screening Array (Illumina). We identified 39 SNPs that mapped to 13 chromosomal regions to be associated with antibody response to the vaccine; these included SNPs on genes LRRC28 (15q26.3), RGS7 (1q43), PTPRD (9p23), CERKL (2q31.3), DGKB (7p21.2), and TCF4 (18q21.2). Many of these loci are known to be associated with various blood cell traits, autoimmune traits and responses to other vaccines; these genes are involved in immune related functions, including TLR response, JAK–STAT signalling, phagocytosis and immune homeostasis.

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References

  • Benjamini Y. and Hochberg Y. 1995 Controlling the false discovery rate: A practical and powerful approach to multiple testing. J. R Stat. Soc. Ser. B (Methodological) 57, 289–300.

    MathSciNet  Google Scholar 

  • Chang C. C., Carson C. C., Tellier L. C., Vattikuti S., Purcell S. M. and Lee J. J. 2015 Second-generation PLINK: rising to the challenge of larger and richer datasets. GigaScience 4, s13742–s14015.

    Article  Google Scholar 

  • Chen D. D., Lu L. F., Xiong F., Wang X. L., Jiang J. Y., Zhang C. et al. 2022 Zebrafish CERKL enhances host TBK1 stability and simultaneously degrades viral protein via ubiquitination modulation. J. Immunol. 208, 2196–2206.

    Article  CAS  PubMed  Google Scholar 

  • Chen W. H., Neuzil K. M., Boyce C. R., Pasetti M. F., Reymann M. K., Martellet L. et al. 2018 Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine containing serogroups A, C, Y, W, and X in healthy adults: a phase 1, single-centre, double-blind, randomised, controlled study. Lancet Infect. Dis. 18, 1088–1096.

    Article  CAS  PubMed  Google Scholar 

  • Coppiello G., Collantes M., Sirerol-Piquer M. S., Vandenwijngaert S., Schoors S., Swinnen M. et al. 2015 Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation 131, 815–826.

    Article  CAS  PubMed  Google Scholar 

  • Das S., Forer L., Schönherr S., Sidore C., Locke A. E., Kwong A. et al. 2016 Next-generation genotype imputation service and methods. Nat. Genet. 48, 1284–1287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garg R., Akhade A. S., Yadav J. and Qadri A. 2015 MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG. Innate Immune. 21, 778–783.

    Article  CAS  Google Scholar 

  • GBD 2017 Typhoid and Paratyphoid Collaborators 2019 The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect. Dis. 19, 369–381.

    Article  Google Scholar 

  • Graf C., Zemann B., Rovina P., Urtz N., Schanzer A., Reuschel R. et al. 2008 Neutropenia with impaired immune response to Streptococcus pneumoniae in ceramide kinase-deficient mice. J. Immunol. 180, 3457–3466.

    Article  CAS  PubMed  Google Scholar 

  • Hausmann O. N., Hu W. H., Keren-Raifman T., Witherow D. S., Wang Q., Levay K. et al. 2002 Spinal cord injury induces expression of RGS7 in microglia/macrophages in rats. Eur. J. Neurosci. 15, 602–612.

    Article  PubMed  Google Scholar 

  • Jarret A., Jackson R., Duizer C., Healy M. E., Zhao J., Rone J. M. et al. 2020 Enteric nervous system-derived IL-18 orchestrates mucosal barrier immunity. Cell 180, 50–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin C., Gibani M. M., Moore M., Juel H. B., Jones E., Meiring J. et al. 2017 Efficacy and immunogenicity of a Vi-tetanus toxoid conjugate vaccine in the prevention of typhoid fever using a controlled human infection model of Salmonella Typhi: a randomised controlled, phase 2b trial. Lancet 390, 2472–2480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy R. B., Ovsyannikova I. G., Haralambieva I. H., Lambert N. D., Pankratz V. S. and Poland G. A. 2014 Genome-wide SNP associations with rubella-specific cytokine responses in measles-mumps-rubella vaccine recipients. Immunogenetics 66, 493–499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy R. B., Ovsyannikova I. G., Pankratz V. S., Haralambieva I. H., Vierkant R. A., Jacobson R. M. et al. 2012a Genome-wide genetic associations with IFNγ response to smallpox vaccine. Hum. Genet. 131, 1433–1451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kennedy R. B., Ovsyannikova I. G., Pankratz V. S., Haralambieva I. H., Vierkant R. A. and Poland G. A. 2012b Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. Hum. Genet. 131, 1403–1421.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim M., Morales L. D., Jang I.-S., Cho Y.-Y. and Kim D. J. 2018 Protein Tyrosine Phosphatases as Potential Regulators of STAT3 Signaling. Int. J. Mol. Sci. 19, 2708.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim S., Lee K. S., Pak G. D., Excler J.-L., Sahastrabuddhe S., Marks F. et al. 2019 Spatial and temporal patterns of typhoid and paratyphoid fever outbreaks: A Worldwide Review, 1990–2018. Clin. Inf. Dis. 69, S499–S509.

    Article  Google Scholar 

  • Lin H.-H., Chen H. L., Weng C.-C., Janapatla R. P., Chen C. L. and Chiu C.-H. 2021 Activation of apoptosis by Salmonella pathogenicity island-1 effectors through both intrinsic and extrinsic pathways in Salmonella-infected macrophages. J. Microbiol. Immunol. Inf. 54, 616–626.

    Article  CAS  Google Scholar 

  • Li P., Shi D., Shen W., Shi S., Guo X., Li J. et al. 2022 Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines. Front. Immunol. 13, 1054147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li S., Sullivan N. L., Rouphael N., Yu T., Banton S., Maddur M. S. et al. 2017 Metabolic phenotypes of response to vaccination in humans. Cell 169, 862–877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Majumder P. P., Staats H. F., Sarkar-Roy N., Varma B., Ghosh T., Maiti S. et al. 2009 Genetic determinants of immune-response to a polysaccharide vaccine for typhoid. HUGO J. 3, 17–30.

    Article  PubMed  Google Scholar 

  • Manoharan I., Swafford D., Shanmugam A., Patel N., Prasad P. D., Thangaraju M. et al. 2021 Activation of transcription factor 4 in dendritic cells controls Th1/Th17 responses and autoimmune neuroinflammation. J. Immunol. 207, 1428–1436.

    Article  CAS  PubMed  Google Scholar 

  • Ma S., Wan X., Deng Z., Shi L., Hao C., Zhou Z. et al. 2017 Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs. J. Exp. Med. 214, 1471–1491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masuho I., Balaji S., Muntean B. S., Skamangas N. K., Chavali S., Tesmer J. J. G. et al. 2020 A global map of G protein signaling regulation by RGS proteins. Cell 183, 503–521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Milet J., Sabbagh A., Migot-Nabias F., Luty A. J. F., Gaye O., Garcia A. et al. 2016 Genome-wide association study of antibody responses to Plasmodium falciparum candidate vaccine antigens. Genes Immu. 17, 110–117.

    Article  CAS  Google Scholar 

  • Ng A. C. Y., Eisenberg J. M., Heath R. J. W., Huett A., Robinson M. C., Nau G. J. et al. 2011 Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity. Proc. Natl. Acad. Sci. USA 108, 4631–4638.

    Article  ADS  CAS  PubMed  Google Scholar 

  • Ochiai R. L., Khan M. I., Soofi S. B., Sur D., Kanungo S., You Y. A. et al. 2014 Immune responses to Vi capsular polysaccharide typhoid vaccine in children 2 to 16 years old in Karachi, Pakistan, and Kolkata. India. Clin. Vaccine Immunol. 21, 661–666.

    Article  PubMed  Google Scholar 

  • O’Connor D., Png E., Khor C. C., Snape M. D., Hill A. V. S., van der Klis F. et al. 2019 Common genetic variations associated with the persistence of immunity following childhood immunization. Cell Rep. 27, 3241–3253.

    Article  PubMed  Google Scholar 

  • O’Connor D. and Pollard A. J. 2013 Characterizing vaccine responses using host genomic and transcriptomic analysis. Clin. Inf. Dis. 57, 860–869.

    Article  Google Scholar 

  • Ovsyannikova I. G., Kennedy R. B., O’Byrne M., Jacobson R. M., Pankratz V. S. and Poland G. A. 2012 Genome-wide association study of antibody response to smallpox vaccine. Vaccine 30, 4182–4189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parween F., Yadav J. and Qadri A. 2019 The virulence polysaccharide of salmonella typhi suppresses activation of Rho family GTPases to limit inflammatory responses from epithelial cells. Front. Cell. Inf. Microbiol. 9, 141.

    Article  CAS  Google Scholar 

  • Piccio L., Vermi W., Boles K. S., Fuchs A., Strader C. A., Facchetti F. et al. 2005 Adhesion of human T cells to antigen-presenting cells through SIRPβ2-CD47 interaction costimulates T-cell proliferation. Blood 105, 2421–2427.

    Article  CAS  PubMed  Google Scholar 

  • Pickering M., Cumiskey D. and O’Connor J. J. 2005 Actions of TNF-alpha on glutamatergic synaptic transmission in the central nervous system. Exp. Physiol. 90, 663–670.

    Article  CAS  PubMed  Google Scholar 

  • Piepoli A., Palmieri O., Maglietta R., Panza A., Cattaneo E., Latiano A. et al. 2012 The expression of leucine-rich repeat gene family members in colorectal cancer. Exp. Biol. Med. 237, 1123–1128.

    Article  CAS  Google Scholar 

  • Price A. L., Patterson N. J., Plenge R. M., Weinblatt M. E., Shadick N. A. and Reich D. 2006 Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909.

    Article  CAS  PubMed  Google Scholar 

  • Rodriguez-Fraticelli A. E., Weinreb C., Wang S.-W., Migueles R. P., Jankovic M., Usart M. et al. 2020 Single-cell lineage tracing unveils a role for TCF15 in haematopoiesis. Nature 583, 585–589.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  • Sinha S., Renavikar P. S., Crawford M. P., Steward-Tharp S. M., Brate A., Tsalikian E. et al. 2020 Altered expression of SIRPγ on the T-cells of relapsing remitting multiple sclerosis and type 1 diabetes patients could potentiate effector responses from T-cells. PLoS One 15, e0238070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Słomian D., Szyda J., Dobosz P., Stojak J., Michalska-Foryszewska A., Sypniewski M. et al. 2023 Better safe than sorry—Whole-genome sequencing indicates that missense variants are significant in susceptibility to COVID-19. PLoS One 18, e0279356.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sur D., Ochiai R. L., Bhattacharya S. K., Ganguly N. K., Ali M., Manna B. et al. 2009 A cluster-randomized effectiveness trial of Vi typhoid vaccine in India. New Engl. J. Med. 361, 335–344.

    Article  CAS  PubMed  Google Scholar 

  • Thibord F., Chan M. V., Chen M.-H. and Johnson A.-D. 2022. A year of COVID-19 GWAS results from the GRASP portal reveals potential genetic risk factors. HGG Adv. 3.

  • Tian C., Hromatka B. S., Kiefer A. K., Eriksson N., Noble S. M., Tung J. Y. et al. 2017 Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections. Nat. Commun. 8, 599.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  • Vuckovic D., Bao E. L., Akbari P., Lareau C. A., Mousas A., Jiang T. et al. 2020 The polygenic and monogenic basis of blood traits and diseases. Cell 182, 1214–1231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang K., Li M. and Hakonarson H. 2010 ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ward L. D. and Kellis M. 2012 HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40, D930–D934.

    Article  CAS  PubMed  Google Scholar 

  • Wenger Y., Buzgariu W., Reiter S. and Galliot B. 2014 Injury-induced immune responses in Hydra. Sem. Immunol. 26, 277–294.

    Article  CAS  Google Scholar 

  • Wu W. B. 2008 On false discovery control under dependence. Ann. Stat. 36, 364–380.

    Article  MathSciNet  Google Scholar 

  • Yamamoto M., Tanaka T., Hozumi Y., Saino-Saito S., Nakano T., Tajima K. et al. 2014 Expression of mRNAs for the diacylglycerol kinase family in immune cells during an inflammatory reaction. Biomed. Res. 35, 61–68.

    Article  CAS  PubMed  Google Scholar 

  • Yang R., Qu C., Zhou Y., Konkel J. E., Shi S., Liu Y. et al. 2015 Hydrogen sulfide promotes Tet1- and Tet2-mediated Foxp3 demethylation to drive regulatory T cell differentiation and maintain immune homeostasis. Immunity 43, 251–263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y.-A., Chong A. and Song J. 2018 Why is eradicating typhoid fever so challenging: implications for vaccine and therapeutic design. Vaccines 6, 45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X., Guo A., Yu J., Possemato A., Chen Y., Zheng W. et al. 2007 Identification of STAT3 as a substrate of receptor protein tyrosine phosphatase T. Proc. Natl. Acad. Sci. 104, 4060–4064.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by the Indian Council of Medical Research (ICMR, Government of India) and the Council of Scientific and Industrial Research (CSIR, Government of India). VLR was supported by CSIR-Direct-Senior Research Fellowship (09/1033(0008)/2019-EMR-I). PPM acknowledges his National Science Chair fellowship (SB/NSC/2019/04) from Department of Science and Technology, Science and Engineering Research Board (DST-SERB), Government of India, and the National Institute of Biomedical Genomics, Kalyani, for providing facilities for the conduct of this study, especially genotype data generation, when he was associated with the Institute. We thank Mr Bijan B. Bairagya, Mr Indranil Bagchi, Dr Arup Ghosh, and Mr Sayan Das for assistance with handling of DNA samples and genotyping assay. We thank Dr Analabha Basu and Dr Arindam Maitra for valuable suggestions.

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Authors and Affiliations

  1. National Institute of Biomedical Genomics, P.O.: N.S.S., Kalyani, 741 251, India

    Vijay Laxmi Roy

  2. Exsegen Genomics Research Pvt. Ltd., Hyderabad, 500 033, India

    Vijay Laxmi Roy

  3. John C. Martin Centre for Liver Research and Innovations, Kolkata, 700 150, India

    Partha Pratim Majumder

  4. Indian Statistical Institute, 203 Barrackpore Trunk Road, Kolkata, 700 108, India

    Partha Pratim Majumder

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  1. Vijay Laxmi Roy
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  2. Partha Pratim Majumder
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PPM conceptualised, designed and supervised all aspects of the study. VLR provided additional inputs to the methodological aspects of the study, generated the genomewide data and performed data analysis. Both authors jointly drafted the manuscript.

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Correspondence to Partha Pratim Majumder.

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Corresponding editor: Ashwin Dalal

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Roy, V.L., Majumder, P.P. Genomic determinants of antibody response to a typhoid vaccine in Indian recipients. J Genet 103, 12 (2024). https://doi.org/10.1007/s12041-024-01463-z

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