Influence of protein fold stability on immunogenicity and its implications for vaccine design

References

• Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med. 2013;19(12):1597–1608.
   PubMed Web of Science ®Google Scholar
• Rock KL, Reits E, Neefjes J. Present yourself! By MHC class I and MHC class II molecules. Trends Immunol. 2016;37:724–737.
   PubMed Web of Science ®Google Scholar
• Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem. 2009;78:477–513.
   PubMed Web of Science ®Google Scholar
• Neefjes J, Jongsma ML, Paul P, et al. Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol. 2011;11(12):823–836.
   PubMed Web of Science ®Google Scholar
• Cresswell P, Bangia N, Dick T, et al. The nature of the MHC class I peptide loading complex. Immunol Rev. 1999;172:21–28.
   PubMed Web of Science ®Google Scholar
• Garstka MA, Fish A, Celie PH, et al. The first step of peptide selection in antigen presentation by MHC class I molecules. Proc Natl Acad Sci USA. 2015;112(5):1505–1510.
   PubMed Web of Science ®Google Scholar
• Wearsch PA, Cresswell P. Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer. Nat Immunol. 2007;8(8):873–881.
   PubMed Web of Science ®Google Scholar
• Bonifaz LC, Bonnyay DP, Charalambous A, et al. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. J Exp Med. 2004;199(6):815–824.
   PubMed Web of Science ®Google Scholar
• Lim JP, Gleeson PA. Macropinocytosis: an endocytic pathway for internalising large gulps. Immunol Cell Biol. 2011;89(8):836–843.
   PubMed Web of Science ®Google Scholar
• Stuart LM, Ezekowitz RA. Phagocytosis: elegant complexity. Immunity. 2005;22(5):539–550.
   PubMed Web of Science ®Google Scholar
• Roche PA, Furuta K. The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol. 2015;15(4):203–216.
   PubMed Web of Science ®Google Scholar
• McCormick PJ, Martina JA, Bonifacino JS. Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proc Natl Acad Sci USA. 2005;102(22):7910–7915.
   PubMed Web of Science ®Google Scholar
• Ghosh P, Amaya M, Mellins E, et al. The structure of an intermediate in class II MHC maturation: CLIP bound to HLA-DR3. Nature. 1995;378(6556):457–462.
   PubMed Web of Science ®Google Scholar
• Denzin LK, Cresswell P. HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading. Cell. 1995;82(1):155–165.
   PubMed Web of Science ®Google Scholar
• Chow A, Toomre D, Garrett W, et al. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature. 2002;418(6901):988–994.
   PubMed Web of Science ®Google Scholar
• Sercarz EE, Maverakis E. MHC-guided processing: binding of large antigen fragments. Nat Rev Immunol. 2003;3(8):621–629.
   PubMed Web of Science ®Google Scholar
• Kim A, Hartman IZ, Poore B, et al. Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources. Nat Commun. 2014;5:5369.
   PubMed Web of Science ®Google Scholar
• Joffre OP, Segura E, Savina A, et al. Cross-presentation by dendritic cells. Nat Rev Immunol. 2012;12(8):557–569.
   PubMed Web of Science ®Google Scholar
• Faure F, Mantegazza A, Sadaka C, et al. Long-lasting cross-presentation of tumor antigen in human DC. Eur J Immunol. 2009;39(2):380–390.
   PubMed Web of Science ®Google Scholar
• Crotty S. T follicular helper cell differentiation, function, and roles in disease. Immunity. 2014;41(4):529–542.
   PubMed Web of Science ®Google Scholar
• Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol. 2010;28:445–489.
   PubMed Web of Science ®Google Scholar
• van Panhuys N, Signal Strength TCR. Alters T-DC activation and interaction times and directs the outcome of differentiation. Front Immunol. 2016;7:6.
   PubMed Web of Science ®Google Scholar
• Yamane H, Paul WE. Early signaling events that underlie fate decisions of naive CD4(+) T cells toward distinct T-helper cell subsets. Immunol Rev. 2013;252(1):12–23.
   PubMed Web of Science ®Google Scholar
• O’Quinn DB, Palmer MT, Lee YK, et al. Emergence of the Th17 pathway and its role in host defense. Adv Immunol. 2008;99:115–163.
   PubMed Web of Science ®Google Scholar
• Sutton C, Brereton C, Keogh B, et al. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med. 2006;203(7):1685–1691.
   PubMed Web of Science ®Google Scholar
• Zou W, Restifo NP. T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol. 2010;10(4):248–256.
   PubMed Web of Science ®Google Scholar
• Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.
   PubMed Web of Science ®Google Scholar
• Bettelli E, Korn T, Oukka M, et al. Induction and effector functions of T(H)17 cells. Nature. 2008;453(7198):1051–1057.
   PubMed Web of Science ®Google Scholar
• Azizi G, Yazdani R, Mirshafiey A. Th22 cells in autoimmunity: a review of current knowledge. Eur Ann Allergy Clin Immunol. 2015;47(4):108–117.
   PubMed Web of Science ®Google Scholar
• Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. 2012;30:531–564.
   PubMed Web of Science ®Google Scholar
• Schmitt EG, Williams CB. Generation and function of induced regulatory T cells. Front Immunol. 2013;4:152.
   PubMed Web of Science ®Google Scholar
• Vinuesa CG, Linterman MA, Yu D, et al. Follicular helper T cells. Annu Rev Immunol. 2016;34:335–368.
   PubMed Web of Science ®Google Scholar
• Constant S, Pfeiffer C, Woodard A, et al. Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med. 1995;182(5):1591–1596.
   PubMed Web of Science ®Google Scholar
• Gottschalk RA, Corse E, Allison JP. TCR ligand density and affinity determine peripheral induction of Foxp3 in vivo. J Exp Med. 2010;207(8):1701–1711.
   PubMed Web of Science ®Google Scholar
• Gottschalk RA, Hathorn MM, Beuneu H, et al. Distinct influences of peptide-MHC quality and quantity on in vivo T-cell responses. Proc Natl Acad Sci USA. 2012;109(3):881–886.
   PubMed Web of Science ®Google Scholar
• van Panhuys N, Klauschen F, Germain RN. T-cell-receptor-dependent signal intensity dominantly controls CD4(+) T cell polarization in vivo. Immunity. 2014;41(1):63–74.
   PubMed Web of Science ®Google Scholar
• Milner JD, Fazilleau N, McHeyzer-Williams M, et al. Cutting edge: lack of high affinity competition for peptide in polyclonal CD4+ responses unmasks IL-4 production. J Immunol. 2010;184(12):6569–6573.
   PubMed Web of Science ®Google Scholar
• Fazilleau N, McHeyzer-Williams LJ, Rosen H, et al. The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol. 2009;10(4):375–384.
   PubMed Web of Science ®Google Scholar
• Gomez-Rodriguez J, Wohlfert EA, Handon R, et al. Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med. 2014;211(3):529–543.
   PubMed Web of Science ®Google Scholar
• Fagain CO. Understanding and increasing protein stability. Biochim Biophys Acta. 1995;1252(1):1–14.
   PubMed Web of Science ®Google Scholar
• Kishore D, Kundu S, Kayastha AM. Thermal, chemical and pH induced denaturation of a multimeric beta-galactosidase reveals multiple unfolding pathways. PLoS One. 2012;7(11):e50380.
   PubMed Web of Science ®Google Scholar
• Nick Pace C, Scholtz JM, Grimsley GR. Forces stabilizing proteins. FEBS Lett. 2014;588(14):2177–2184.
   PubMed Web of Science ®Google Scholar
• Sinnathamby G, Maric M, Cresswell P, et al. Differential requirements for endosomal reduction in the presentation of two H2-E(d)-restricted epitopes from influenza hemagglutinin. J Immunol. 2004;172(11):6607–6614.
   PubMed Web of Science ®Google Scholar
• Swoboda I, Bugajska-Schretter A, Linhart B, et al. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol. 2007;178(10):6290–6296.
   PubMed Web of Science ®Google Scholar
• Thalhamer T, Dobias H, Stepanoska T, et al. Designing hypoallergenic derivatives for allergy treatment by means of in silico mutation and screening. J Allergy Clin Immunol. 2010;125(4):926–934e910.
   PubMed Web of Science ®Google Scholar
• Machado Y, Freier R, Scheiblhofer S, et al. Fold stability during endolysosomal acidification is a key factor for allergenicity and immunogenicity of the major birch pollen allergen. J Allergy Clin Immunol. 2016;137(5):1525–1534.
   PubMed Web of Science ®Google Scholar
• Joyce MG, Zhang B, Ou L, et al. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Mol Biol. 2016;23(9):811–820.
   PubMed Web of Science ®Google Scholar
• Krarup A, Truan D, Furmanova-Hollenstein P, et al. A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nat Commun. 2015;6:8143.
   PubMed Web of Science ®Google Scholar
• Kwon YD, Pancera M, Acharya P, et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015;22(7):522–531.
   PubMed Web of Science ®Google Scholar
• Liang B, Surman S, Amaro-Carambot E, et al. Enhanced neutralizing antibody response induced by respiratory syncytial virus prefusion F protein expressed by a vaccine candidate. J Virol. 2015;89(18):9499–9510.
   PubMed Web of Science ®Google Scholar
• Wahome N, Sully E, Singer C, et al. Novel ricin subunit antigens with enhanced capacity to elicit toxin-neutralizing antibody responses in mice. J Pharm Sci. 2016;105(5):1603–1613.
   PubMed Web of Science ®Google Scholar
• Montero D, Tachibana C, Rahr Winther J, et al. Intracellular glutathione pools are heterogeneously concentrated. Redox Biol. 2013;1:508–513.
   PubMed Web of Science ®Google Scholar
• Fox CB, Kramer RM, Barnes VL, et al. Working together: interactions between vaccine antigens and adjuvants. Ther Adv Vaccines. 2013;1(1):7–20.
   PubMedGoogle Scholar
• Wagner L, Verma A, Meade BD, et al. Structural and immunological analysis of anthrax recombinant protective antigen adsorbed to aluminum hydroxide adjuvant. Clin Vaccine Immunol. 2012;19(9):1465–1473.
   PubMed Web of Science ®Google Scholar
• Accapezzato D, Visco V, Francavilla V, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med. 2005;202(6):817–828.
   PubMed Web of Science ®Google Scholar
• Delamarre L, Couture R, Mellman I, et al. Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis. J Exp Med. 2006;203(9):2049–2055.
   PubMed Web of Science ®Google Scholar
• Liu W, Onda M, Kim C, et al. A recombinant immunotoxin engineered for increased stability by adding a disulfide bond has decreased immunogenicity. Protein Eng Des Sel. 2012;25(1):1–6.
   PubMed Web of Science ®Google Scholar
• Mansfeld J, Vriend G, Dijkstra BW, et al. Extreme stabilization of a thermolysin-like protease by an engineered disulfide bond. J Biol Chem. 1997;272(17):11152–11156.
   PubMed Web of Science ®Google Scholar
• Lee B, Vasmatzis G. Stabilization of protein structures. Curr Opin Biotechnol. 1997;8(4):423–428.
   PubMed Web of Science ®Google Scholar
• Nakamura H, Ohkuri T, So T, et al. Relationship between the magnitude of IgE production in mice and conformational stability of the house dust mite allergen, Der p 2. Biochim Biophys Acta. 2016;1860:2279–2284.
   PubMed Web of Science ®Google Scholar
• Arancibia S, Del Campo M, Nova E, et al. Enhanced structural stability of Concholepas hemocyanin increases its immunogenicity and maintains its non-specific immunostimulatory effects. Eur J Immunol. 2012;42(3):688–699.
   PubMed Web of Science ®Google Scholar
• So T, Ito HO, Koga T, et al. Depression of T-cell epitope generation by stabilizing hen lysozyme. J Biol Chem. 1997;272(51):32136–32140.
   PubMed Web of Science ®Google Scholar
• Wong SS, Wong LJ. Chemical crosslinking and the stabilization of proteins and enzymes. Enzyme Microb Technol. 1992;14(11):866–874.
   PubMed Web of Science ®Google Scholar
• Li J, Koehl P. Geometric potentials for computational protein sequence design. Methods Mol Biol. 2017;1529:125–138.
   PubMedGoogle Scholar
• Modarres HP, Mofrad MR, Sanati-Nezhad A. Protein thermostability engineering. Rsc Adv. 2016;6(116):115252–115270.
   Web of Science ®Google Scholar
• Laimer J, Hofer H, Fritz M, et al. MAESTRO – multi agent stability prediction upon point mutations. BMC Bioinformatics. 2015;16:116.
   PubMed Web of Science ®Google Scholar
• Laimer J, Hiebl-Flach J, Lengauer D, et al. MAESTROweb: a web server for structure-based protein stability prediction. Bioinformatics. 2016;32(9):1414–1416.
   PubMed Web of Science ®Google Scholar
• Thai R, Moine G, Desmadril M, et al. Antigen stability controls antigen presentation. J Biol Chem. 2004;279(48):50257–50266.
   PubMed Web of Science ®Google Scholar
• So T, Ito H, Hirata M, et al. Contribution of conformational stability of hen lysozyme to induction of type 2 T-helper immune responses. Immunology. 2001;104(3):259–268.
   PubMed Web of Science ®Google Scholar
• Ohkuri T, Nagatomo S, Oda K, et al. A protein’s conformational stability is an immunologically dominant factor: evidence that free-energy barriers for protein unfolding limit the immunogenicity of foreign proteins. J Immunol. 2010;185(7):4199–4205.
   PubMed Web of Science ®Google Scholar
• Nguyen HN, Steede NK, Robinson JE, et al. Conformational instability governed by disulfide bonds partitions the dominant from subdominant helper T-cell responses specific for HIV-1 envelope glycoprotein gp120. Vaccine. 2015;33(25):2887–2896.
   PubMed Web of Science ®Google Scholar
• Delamarre L, Pack M, Chang H, et al. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science. 2005;307(5715):1630–1634.
   PubMed Web of Science ®Google Scholar
• Lecoq A, Moine G, Bellanger L, et al. Increasing the humoral immunogenic properties of the HIV-1 Tat protein using a ligand-stabilizing strategy. Vaccine. 2008;26(21):2615–2626.
   PubMed Web of Science ®Google Scholar
• Turbant S, Martinon F, Moine G, et al. Cynomolgus macaques immunized with two HIV-1 Tat stabilized proteins raise strong and long-lasting immune responses with a pattern of Th1/Th2 response differing from that in mice. Vaccine. 2009;27(39):5349–5356.
   PubMed Web of Science ®Google Scholar
• Yumura K, Ui M, Doi H, et al. Mutations for decreasing the immunogenicity and maintaining the function of core streptavidin. Protein Sci. 2013;22(2):213–221.
   PubMed Web of Science ®Google Scholar
• Kodama T, Hamakubo T, Doi H, et al. Hypo-immunogenic streptavidin and use thereof. 2010. International Patent Application WO/2010/095455 (August 26, 2010).
   Google Scholar
• Porta C, Kotecha A, Burman A, et al. Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen. PLoS Pathog. 2013;9(3):e1003255.
   PubMed Web of Science ®Google Scholar
• McLellan JS, Chen M, Joyce MG, et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science. 2013;342(6158):592–598.
   PubMed Web of Science ®Google Scholar
• Hosken NA, Shibuya K, Heath AW, et al. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med. 1995;182(5):1579–1584.
   PubMed Web of Science ®Google Scholar
• Maric M, Arunachalam B, Phan UT, et al. Defective antigen processing in GILT-free mice. Science. 2001;294(5545):1361–1365.
   PubMed Web of Science ®Google Scholar
• Qi H, Egen JG, Huang AY, et al. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science. 2006;312(5780):1672–1676.
   PubMed Web of Science ®Google Scholar
• Langley JM, Aggarwal N, Toma A, et al. A randomized, controlled, observer-blinded phase 1 study of the safety and immunogenicity of a respiratory syncytial virus vaccine with or without alum adjuvant. J Infect Dis. 2017;215(1):24–33.
   PubMed Web of Science ®Google Scholar
• Asam C, Batista AL, Moraes AH, et al. Bet v 1 – a Trojan horse for small ligands boosting allergic sensitization? Clin Exp Allergy. 2014;44(8):1083–1093.
   PubMed Web of Science ®Google Scholar
• Grutsch S, Fuchs JE, Freier R, et al. Ligand binding modulates the structural dynamics and compactness of the major birch pollen allergen. Biophys J. 2014;107(12):2972–2981.
   PubMed Web of Science ®Google Scholar
• van der Laan JW, Gould S, Tanir JY, et al. Adjuvants safety project C. Safety of vaccine adjuvants: focus on autoimmunity. Vaccine. 2015;33(13):1507–1514.
   PubMed Web of Science ®Google Scholar