Immunogenicity Testing in the Era of Reverse and Systems Vaccinology
Abstract views: 151
/ 
PDF downloads: 18
Authors
-
Ajit Singh
LUVAS, Hisar
http://orcid.org/0000-0003-0620-9879
Keywords:
Immunogenicity testing, ex vivo/in vivo methods, rational vaccine discovery, vaccine efficacy evaluationAbstract
Immunogenicity testing is an essential step in the preclinical phase of vaccine development and the quality control of commercial vaccines. This often employs protection of the host against pathogen challenge. Alternatively, ex vivo or in vitro measurement of immune parameters that correlate with protection may be done. Immune markers of infection, disease and vaccine-induced protection are being searched by employing modern approaches, including immunomics, computational immunology and systems vaccinology. Various humoral and cellular immune parameters are suggested as potential correlates or surrogates of protection induced by human and animal vaccines. Ex vivo and in vitro assays that measure immune cell proliferation, phenotypes, signaling, cytotoxicity, production of cytokines, antibodies, etc. provide an early and/or ethically improved readout of vaccine immunogenicity, thereby saving costs, time and animal suffering. Whole blood, peripheral blood mononuclear cells (PBMCs) or monocyte-derived dendritic cells (MoDCs)-co-cultured with PBMCs or T cell subsets can be used in these assays to examine primary or recall immune responses. In vitro antigen-primed MoDC: T cell co-culture models and artificial immune systems are being standardized and validated for evaluation of vaccine immunogens. The usefulness of immunogenicity testing ‘outside animals’ is likely to increase in future, with its focus on measuring the correlates of protection or surrogates of B and T cell immunity, which are being established for increasing number of current and future vaccines in the era of ‘reverse’ and ‘systems’ vaccinology.
References
Abbas AK, Lichtman AH, Pillai S, editors. Cellular and Molecular Immunology, 9th Edition. Elsevier Publishers, Philadelphia, USA; 2018.
Adams GL, Khare S, Lawhon SD et al (2011) Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: Linking systems biology with vaccine development. Vaccine 29: 7197-7206.
Adu-Bobie J, Capecchi B, Serruto D et al (2003) Two years into reverse vaccinology. Vaccine 21: 605-610.
Ahlborg N, Axelsson B (2012) Dual- and triple-color fluorospot. Methods Mol Biol 792: 77-85.
Alter G, Malenfant JM, Altfeld M (2004) CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 29(1-2): 15-22.
Altman JD, Moss PA, Goulder PJ et al (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274: 94.
Amanna IJ, Slifka MK (2011) Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology 411: 206-215.
Bachy M, Bonnin-Rivalland A, Tilliet V et al (1999) β galactosidase release as an alternative to chromium release in cytotoxic T-cell assays. J Immunol Methods 230(1-2): 37-46.
Brosterhus H, Brings S, Leyendeckers H et al (1999) Enrichment and detection of live antigen-specific CD4+ and CD8+ T cells based on cytokine secretion. Eur J Immunol 29: 4053.
Brunner KT, Mauel J, Cerottini JC et al (1968) Quantitative assay of the lytic action of immune lymphoid cells on 51-Cr-labelled allogeneic target cells in vitro; inhibition by isoantibody and by drugs. Immunology 14(2): 181-196.
Buonaguro L, Wang E, Tornesello ML et al (2011) Systems biology applied to vaccine and immunotherapy development. BMC Systems Biol 5: 146
Castelli M, Cappelletti F, Diotti RA et al (2013) Peptide-based vaccinology: Experimental and computational approaches to target hypervariable viruses through the fine characterization of protective epitopes recognized by monoclonal antibodies and the identification of T-cell-activating peptide. Hindawi Clin Develop Immunol 2013, Article ID 521231, 12 pages.
Charleston B, Graham SP (2018) Recent advances in veterinary applications of structural vaccinology. Curr Opin Virol 29: 33–38.
Clinton J, Shapiro B (2015) In vitro differentiation of macrophages and dendritic cells from primary human CD14+ monocytes. ATCC Application Notes (Ap Note no. 21).
Coffman RL, Sher A, Seder RA (2010) Vaccine adjuvants: putting innate immunity to work. Immunity 33(4): 492-503.
Cohen T, Moise L, Ardito M et al (2010) A method for individualizing the prediction of immunogenicity of protein vaccines and biologic therapeutics: Individualized T cell epitope measure (iTEM). Hindawi J Biomed Biotechnol 2010, Article ID 961752, 7 pages.
Coligan JE, Hogquist MK, Margulies DH et al, editors. Current Protocols in Immunology. Series of Volumes Online ISSN:1934-368X. Publishers: John Wiley & Sons, Inc., USA; 2002-2018.
Crotty S, Aubert RD, Glidewell J et al (2004) Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system. J Immunol Methods 286(1-2): 111-122.
Crowther JR, editor. The ELISA Guidebook. In: Methods in Molecular Biology. Humana Press, Totowa, NJ, USA; 2001. pp.1-421.
Cui J, Bystryn JC (1992) An improved europium release assay for complement-mediated cytolysis. J Immunol Methods 147(1): 13-19.
Czerkinsky CC, Nilsson LA, Nygren H et al (1983) A solid-phase enzyme-linked immunospot (ELISPOT) assay for enumeration of specific antibody-secreting cells. J Immunol Methods 65(1-2): 109-121.
De Groot AS, McMurry J, Moise L (2008) Prediction of immunogenicity: in silico paradigms, ex vivo and in vivo correlates. Curr Opin Pharmacol 8: 1-7.
Decker T, Lohmann-Matthes ML (1988) A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 115(1): 61-69.
Defawe OD, Fong Y, Vasilyeva E et al (2012) Optimization and qualification of a multiplex bead array to assess cytokine and chemokine production by vaccine-specific cells. J Immunol Methods 382(1-2): 117-128.
Downey JS, Attaf M, Moyle G et al (2011) T-cell signalling in antiretroviral treated, aviraemic HIV-1-positive individuals is present in a raised state of basal activation that contributes to T-cell hypo-responsiveness. AIDS 25(16): 1981-1986.
Furman D, Davis MM (2015) New approaches to understanding the immune response to vaccination and infection. Vaccine 33: 5271-5281.
Gallimore A, Glithero A, Godkin A et al (1998) Induction and exhaustion of lymphocytic chorio-meningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med 187: 1383.
Goodell V, dela Rosa C, Slota M et al (2007) Sensitivity and specificity of tritiated thymidine incorporation and ELISPOT assays in identifying antigen specific T cell immune responses. BMC Immunol 8: 21.
Gupta P, Tayal R, Durgapal H et al (2009) Development of highly sensitive Bicistronic vector based non-radioactive antigen-specific cytotoxicity assay. J Immunol Methods 349(1-2): 28-37.
Herath C, Kumar P, Singh, M et al (2010) Experimental iron-inactivated Pasteurella multocida A:1 vaccine adjuvanted with bacterial DNA is safe and protects chickens from fowl cholera. Vaccine 28: 2284-2289.
Kalyuzhny AE (2005). Editor. Handbook of ELISPOT: Methods & Protocols. Methods Mol Biol 302; Humana Press Inc., Totowa, NJ.
Kapoor S, Singh A, Kadian SK, editors. ‘Modern technologies for production and applications of antibodies for improvement of animal health’, E-book [URL: https://cbp.icar.gov.in/EBook.aspx], Last accessed October 15, 2018.
Knight-Jones TJD, Edmond K, Gubbins S et al (2014) Veterinary and human vaccine evaluation methods. Proc R Soc B 281: 20132839.
Kumar D, Singh A (2005) Salmonella typhimurium grown in iron-rich media, inactivated with ferric chloride and adjuvanted with homologous bacterial DNA is potent and efficacious vaccine in mice. Vaccine 23(48-49): 5590- 5598.
Lanzavecchia A, Fruhwirth A, Perez L et al (2016) Antibody-guided vaccine design: identification of protective epitopes. Curr Opin Immunol 41: 62-67.
Lehmann PV, Zhang W (2012) Unique strengths of ELISPOT for T cell diagnostics. Methods Mol Biol 792: 3-23.
Leif RC, Stein JH, Zucker RM (2004) A short history of the initial application of anti-5-BrdU to the detection and measurement of S phase. Cytometry A 58(1): 45-52.
Lovelace P, Maecker HT (2011) Multiparameter intracellular cytokine staining. Methods Mol Biol 699: 165-178.
Lutz M, Strobl H, Schuler G et al (2017) GM-CSF monocyte-derived cells and Langerhans cells as part of the dendritic cell family. Front Immunol 8: 1388.
Lyons AB (2000) Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods 243(1-2): 147-154.
Maecker HT (2009) Multiparameter flow cytometry monitoring of T cell responses. Methods Mol Biol 485: 375-391.
Mahanty S, Prigent A, Garraud O (2015) Immunogenicity of infectious pathogens and vaccine antigens BMC Immunol 16: 31-36.
McKinnon KM (2018) Flow Cytometry: An Overview. Curr Prot Immunol 120(1): 5.1.1-5.1.11.
Memon SA, Petrak D, Moreno MB et al (1995) A simple assay for examining the effect of transiently expressed genes on programmed cell death. J Immunol Methods 180(1): 15-24.
Moser M, Leo O (2010) Key concepts in immunology. Vaccine 28S: C2–C13p.
Newell EW, Sigal N, Bendall SC et al (2012) Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity 36(1): 142-152.
Novak EJ, Liu AW, Gebe JA et al (1999) MHC class II tetramers identify peptide-specific human CD4+ T cells proliferating in response to influenza A antigen. J Clin Invest 104: R63.
Park KT, ElNaggar MM, Abdellrazeq GS et al (2016) Phenotype and function of CD209+ bovine blood dendritic cells, monocyte-derived- dendritic cells and monocyte-derived macrophages. PLoS ONE 11(10): e0165247.
Pepper M, Jenkins MK (2011) Origins of CD4(+) effector and central memory T cells. Nat Immunol12(6): 467-471.
Plebanski M, Katsara M, Sheng K-C et al (2010) Methods to measure T-cell responses. Exper Rev Vacc 9(6): 595-600.
Plotkin SA (2010) Correlates of protection induced by vaccination. Clin Vacc Immunol 17(7): 1055-1065.
Pulendran B (2014) Systems vaccinology: Probing humanity’s diverse immune systems with vaccines. PNAS (USA) 111(34): 12300-1236.
Puronen CE, Thompson WL, Imamichi H et al (2012) Decreased interleukin 7 responsiveness of T lymphocytes in patients with idiopathic CD4 lymphopenia. J Infect Dis 205(9): 1382-1390.
Reece WH, Pinder M, Gothard PK et al (2004) A CD4+ T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. Nat Med 10(4): 406-410.
Saade F, Gorski SA, Petrovsky N (2012) Pushing the frontiers of T-cell vaccines: accurate measurement of human T-cell responses. Exper Rev Vacc 11(12): 1459-1470.
Sanchez-Trincado JL, Gomez-Perosanz M, Reche PA (2017) Fundamentals and methods for T- and B-cell epitope prediction. Hindawi J Immunol Res 2017, Article ID 2680160, 14 pages.
Shedlock DJ, Talbott KT, Morrow MP et al (2010) Ki-67 staining for determination of rhesus macaque T cell proliferative responses ex vivo. Cytometry A 77(3): 275-284.
Sim WJ, Malinarich F, Fairhurst A-M et al. (2016). Generation of immature, mature and tolerogenic dendritic cells with differing metabolic phenotypes. J Vis Exp (112): e54128.
Singh A (2016) Progress from the traditional vaccines to novel rational vaccine designs. Res & Rev: J Immunol 6(3): 17-31.
Singh A (2017) Next generation immunoassays for infectious diseases of animals. Res Rev J Immunol 7(2): 22-43.
Singh A (2018) Immunology as applied to farm animal welfare: General principles and interventions. Res & Rev: J Immunol 8(1):1–13.
Smith SG, Smits K, Joosten SA et al (2015) Intracellular cytokine staining and flow cytometry: considerations for application in clinical trials of novel tuberculosis vaccines. PLoS ONE 10(9): e0138042.
Swann J, Jamshidi N, Lewis NE et al (2015) Systems analysis of host–parasite interactions. WIREs Systems Biol Med 7: 381-400.
Thakur A, Pedersen LE, Jungersen G (2012) Immune markers and correlates of protection for vaccine induced immune responses. Vaccine 30: 4907-4920.
Vandebriel RJ, Hoefnagel MHN (2012) Dendritic cell-based in vitro assays for vaccine immunogenicity. Human Vacc Immunotherap 8(9): 1323-1325.
Veterinary Immunology Toolbox meeting (Aug. 21-22, 2017). Veterinary Vaccinology Network, The Pirbright Institute, Pirbirght, Surrey, UK.
Waldrop SL, Pitcher CJ, Peterson DM et al (1997) Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry. Evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. J Clin Invest 99(7): 1739-1750.
Warren WL, Drake III D, Moser J et al. (2010). Method for determining the immunogenicity of an antigen. US Patient no. US 7,785,806 B2; Aug. 31, 2010.
Wlodkowic D, Telford W, Skommer J et al (2011) Apoptosis and beyond: Cytometry in studies of programmed cell death. Methods Cell Biol 103: 55-98.
World Health Organization (2013) Correlates of vaccine-induced protection: methods and implications. Published by Initiative for Vaccine Research, Department of Immunizations, Vaccines and Biologicals, WHO, Geneva, 2013.
Yin Y, Mitsonâ€Salazar A, Prussin C (2015). Detection of intracellular cytokines by flow cytometry. Curr Prot Immunol 110(1): 6.24.1-6.24.18
Zuber B, Levitsky V, Jonsson G et al (2005) Detection of human perforin by ELISpot and ELISA: ex vivo identification of virus-specific cells. J Immunol Methods 302(1-2): 13-25.
Downloads
Submitted
Published
Issue
Section
License
The copyright of the articles published in Veterinary Immunology & Biotechnology vests with the Indian Society for Veterinary Immunology & Biotechnology (ISVIB), who has the right to enter into any agreement with any organization in India or abroad engaged in reprography, photocopying, storage and dissemination of information contained in these journals. The ISVIB has no objection in using the material, provided the information is being utilized for academic purpose but not for commercial use.Submission of a manuscript to VIB implies that if and when the manuscript is accepted for publication, the authors agree to automatic transfer of the copyright to the publisher.