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Review

Mechanisms of cellular and humoral immunity through the lens of VLP-based vaccines

ORCID Icon &
Pages 453-469 | Received 22 Sep 2021, Accepted 11 Jan 2022, Published online: 24 Jan 2022

References

  • Pandemic influenza vaccine manufacturing process and timeline: World Health Organization; 2009 [cited 2019 May 6]. Available from: https://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090806/en/
  • Kleid DG, Yansure D, Small B, et al. Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine. Science. 1981;214:1125–1129.
  • Vartak A, Sucheck SJ. Recent advances in subunit vaccine carriers. Vaccines (Basel). 2016;4:12.
  • Speir M, Authier-Hall A, Brooks CR, et al. Glycolipid-peptide conjugate vaccines enhance CD8+ T cell responses against human viral proteins. Sci Rep. 2017;7:14273.
  • Compton BJ, Farrand KJ, Tang C-W, et al. T cell responses and tumour immunity by vaccination with peptides conjugated to a weak NKT cell agonist. Org Biomol Chem. 2019;17:1225–1237.
  • van der Put RMF, Kim TH, Guerreiro C, et al. A synthetic carbohydrate conjugate vaccine candidate against shigellosis: improved bioconjugation and impact of alum on immunogenicity. Bioconjugate Chem. 2016;27:883–892.
  • Yin Z, Huang X. Boosting humoral immune responses to tumor associated carbohydrate antigens with virus-like particles. In: Jimenez-Barbero J, editor. Carbohydrates in drug design and discovery. UK: Royal Society of Chemistry; 2015. p. 132–149.
  • Yin Z, Delaney S, McKay CS, et al. Chemical synthesis of GM2 glycan, bioconjugation with bacteriophage Qβ, and the induction of anticancer antibodies. ChemBioChem. 2016;17:174–180.
  • Patel JM, Vartabedian VF, Kim M-C, et al. Influenza virus-like particles engineered by protein transfer with tumor-associated antigens induces protective antitumor immunity. Biotechnol Bioeng. 2015;112:1102–1110.
  • Wu X, Yin Z, McKay C, et al. Protective epitope discovery and design of MUC1-based vaccine for effective tumor protections in immunotolerant mice. J Am Chem Soc. 2018;140:16596–16609.
  • Lakshminarayanan V, Supekar NT, Wei J, et al. MUC1 vaccines, comprised of glycosylated or non-glycosylated peptides or tumor-derived MUC1, can circumvent immunoediting to control tumor growth in muc1 transgenic mice. PLoS One. 2016;11:e0145920.
  • Ortega-Rivera OA, Pokorski JK, Steinmetz NF. 2021. A single-dose implant-based, trivalent virus-like particle vaccine against “cholesterol checkpoint“ proteins. Adv. Ther. 2100014 ; DOI:https://doi.org/10.1002/adtp.202100014.
  • Crossey E, Amar MJA, Sampson M, et al. A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine. 2015;33:5747–5755.
  • Maphis NM, Peabody J, Crossey E, et al. Qß virus-like particle-based vaccine induces robust immunity and protects against tauopathy. Npj Vaccines. 2019;4:26.
  • Daly SM, Joyner JA, Triplett KD, et al. VLP-based vaccine induces immune control of staphylococcus aureus virulence regulation. Sci Rep. 2016;7:637.
  • Wang P, C-x H, Lang S, et al. Chemical synthesis and immunological evaluation of a potential anti-pertussis vaccine. Angew Chem Int Ed. 2020;59:6451–6458.
  • Wen AM, Steinmetz NF. Design of virus-based nanomaterials for medicine, biotechnology, and energy. Chem Soc Rev. 2016;45:4074–4126.
  • Rohovie MJ, Nagasawa M, Swartz JR. Virus-like particles: next generation nanoparticles for targeted therapeutic delivery. Bioeng Transl Med. 2016;2:43–57.
  • Elsayed H, Nabi G, McKinstry WJ, et al. Intrastructural help: harnessing t helper cells induced by licensed vaccines for improvement of HIV env antibody responses to virus-like particle vaccines. J Virol. 2018;92:e00141–18.
  • Báez-Astúa A, Herráez-Hernández E, Garbi N, et al. Low-dose adenovirus vaccine encoding chimeric hepatitis b virus surface antigen-human papillomavirus type 16 E7 proteins induces enhanced E7-specific antibody and cytotoxic T-cell responses. J Virol. 2005;79:12807–12817.
  • Schiller JT, Lowy DR. Papillomavirus-like particle vaccines. JNCI Monogr. 2000;2000:50–54.
  • Harper DM, Franco EL, Wheeler CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet. 2006;367:1247–1255.
  • Leroux-Roels G, Abraham B, Fourneau M, et al. A comparison of two commercial recombinant vaccines for hepatitis B in adolescents. Vaccine. 2000;19:937–942.
  • Monie A, Hung C-F, Roden R, et al. Cervarix: a vaccine for the prevention of HPV 16, 18-associated cervical cancer. Biol Targets Ther. 2008;2:107–113.
  • Pedersen C, Petaja T, Strauss G, et al. Immunization of early adolescent females with human papillomavirus type 16 and 18 L1 virus-like particle vaccine containing AS04 adjuvant. J Adolesc Health. 2007;40:564–571.
  • Day PM, Kines RC, Thompson CD, et al. In vivo mechanisms of vaccine-induced protection against HPV infection. Cell Host Microbe. 2010;8:260–270.
  • Jegerlehner A, Wiesel M, Dietmeier K, et al. Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies. Vaccine. 2010;28:5503–5512. DOI:https://doi.org/10.1016/j.vaccine.2010.02.103
  • Shukla S, Wang C, Beiss V, et al. Antibody response against cowpea mosaic viral nanoparticles improves in situ vaccine efficacy in ovarian cancer. ACS Nano. 2020;14:2994–3003.
  • Chuan YP, Rivera-Hernandez T, Wibowo N, et al. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine. Biotechnol Bioeng. 2013;110:2343–2351.
  • De Filette M, Martens W, Smet A, et al. Universal influenza a m2e-hbc vaccine protects against disease even in the presence of pre-existing anti-HBc antibodies. Vaccine. 2008;26:6503–6507.
  • Golmohammadi R, Fridborg K, Bundule M, et al. The crystal structure of bacteriophage Qβ at 3.5 Å resolution. Structure. 1996;4:543–554.
  • Rumnieks J, Tars K. Crystal structure of the maturation protein from bacteriophage Qβ. J Mol Biol. 2017;429:688–696.
  • Emery, JHA Analytic control strategy for a VLP-peptide conjugate vaccine 17th Symposium on the interface of regulatory and analytical sciences for biotechnology health products 2013 Washington D. C. , editor. . In: . ; 2013.
  • Fiedler JD, Brown SD, Lau JL, et al. RNA-directed packaging of enzymes within virus-like particles. Angew Chem Int Ed. 2010;49:9648–9651.
  • Suttipun S. Lipopeptide-coated iron oxide nanoparticles and engineered Qβ virus like particles as potential glycoconjugate-based synthetic anticancer vaccines. East Lansing, MI: ProQuest Dissertations Publishing: Michigan State University; 2017.
  • Stable E, Prasuh DE, Udit AK, et al. Unnatural amino acid incorporation into virus-like particles. Bioconjugate Chem. 2008;19:866–875.
  • Pokorski JK, Breitenkamp K, Liepold LO, et al. Functional virus-based polymer-protein nanoparticles by atom transfer radical polymerization. J Am Chem Soc. 2011;133:9242–9245.
  • Pokorski JK, Hovlid ML, Finn MG. Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor. ChemBioChem. 2011;12:2441–2447.
  • Fiedler JD, Fishman MR, Brown SD, et al. Multifunctional enzyme packaging and catalysis in the Qß protein nanoparticle. Biomacromolecules. 2018;19:3945–3957. DOI:https://doi.org/10.1021/acs.biomac.8b00885
  • Yin Z, Wu X, Kaczanowska K, et al. Antitumor humoral and T cell responses by mucin-1 conjugates of bacteriophage Qβ in wild-type mice. ACS Chem Biol. 2018;13:1668–1676.
  • Mohsen MO, Gomes AC, Cabral-Miranda G, et al. Delivering adjuvants and antigens in separate nanoparticles eliminates the need of physical linkage for effective vaccination. J Control Release. 2017;251:92–100.
  • Lim F, Spingola M, Peabody DS. The RNA-binding site of bacteriophage Qβ coat protein. J Biol Chem. 1996;271(50):31839–31845.
  • Yoshimura H, Edwards E, Uchida M, et al. Two-dimensional crystallization of P22 virus-like particles. J Phys Chem B. 2016;120:5938–5944.
  • McCoy K, Douglas T. In vivo packaging of protein cargo inside of virus-like particle P22. In: editors, Wege C, and Lomonossoff G. Virus-derived nanoparticles for advanced technologies. methods in molecular biology. Vol. 1776. New York NY: Humana Press; 2018;295–302.
  • Klug A. The tobacco mosaic virus particle: structure and assembly. Phil Trans R Soc Lond B. 1999;354:531–535.
  • Smith ML, Lindbo JA, Dillard-telm S, et al. Modified tobacco mosaic virus particles as scaffolds for the display of protein antigens for vaccine applications. Virology. 2006;348:475–488.
  • Jegerlehner A, Stormi T, Lipowsky G, et al. Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation. Eur J Immunol. 2002;32:3305–3314.
  • Sungsuwan S, Wu X, Huang X. Evaluation of virus-like particle-based tumor-associated carbohydrate immunogen in a mouse tumor model Imperiali, Barbara. In: Methods enzymol. Vol. 597. New York NY: Elsevier; 2017. p. 359–376.
  • Shao S, Ortega-Rivera OA, Ray S, et al. A scalable manufacturing approach to single dose vaccination against HPV. Vaccines (Basel). 2021;9:66.
  • McCormick AA, Corbo TA, Wykoff-Clary S, et al. TMV-peptide fusion vaccines induce cell-mediated immune responses and tumor protection in two murine models. Vaccine. 2006;24:6414–6423.
  • Guo J, Zhou A, Sun X, et al. Immunogenicity of a virus-like-particle vaccine containing multiple antigenic epitopes of toxoplasma gondii against acute and chronic toxoplasmosis in mice. Front Immunol. 2019;10:592.
  • Jegerlehner A. A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine. 2002;20(25–26):3104–3112.
  • Peng S, Frazer IH, Fernando GJ, et al. Papillomavirus virus-like particles can deliver defined ctl epitopes to the MHC class I pathway. Virology. 1998;240:147–157.
  • Medford A. The generation and immunogenicity of PP7 virus-like particles displaying target antigens. electronic theses and dissertations at UNM digital repository. Albuquerque, NM: University of New Mexico; 2010.
  • Yeager M, Wilson-Kubalek EM, Weiner SG, et al. Supramolecular organization of immature and mature murine leukemia virus revealed by electron cryo-microscopy: implications for retroviral assembly mechanisms. Proc Natl Acad Sci USA. 1998;95:7299–7304.
  • Fluckiger A-C, Bozic J, Diress A, et al. Enveloped virus-like particles (eVLPs) expressing modified forms of zika virus proteins E and NS1 protect mice from zika virus infection bioRxiv 2019 Pre–Print . . DOI:https://doi.org/10.1101/666966.
  • Moreno N, Mena I, Angulo I, et al. Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses. Sci Rep. 2016;6:31844.
  • Guo H, Zhu J, Tan Y, et al. Self-assembly of virus-like particles of rabbit hemorrhagic disease virus capsid protein expressed in Escherichia coli and their immunogenicity in rabbits. Antivir Res. 2016;131:85–91.
  • Laurent S, Vautherot J-F, Madelaine M-F, et al. Recombinant rabbit hemorrhagic disease virus capsid protein expressed in baculovirus self-assembles into viruslike particles and induces protection. J Virol. 1994;68:6794–6798.
  • Mohsen MO, Heath MD, Cabral-Miranda G, et al. Vaccination with nanoparticles combined with micro-adjuvants protects against cancer. J Immunother Cancer. 2020;7:114.
  • Hanafi L-A, Bolduc M, Gagné M-ÈL, et al. Two distinct chimeric potexviruses share antigenic cross-presentation properties of MHC class I epitopes. Vaccine. 2010;28:5617–5626.
  • Denis J, Acosta-Ramirez E, Zhao Y, et al. Development of a universal influenza a vaccine based on the M2e peptide fused to the papaya mosaic virus (PapMV) vaccine platform. Vaccine. 2008;26:3395–3403.
  • Galaway FA, Stockley PG. MS2 virus like particles: a robust, semisynthetic targeted drug delivery platform. Mol Pharm. 2013;10:59–68.
  • Li J, Sun Y, Jia T, et al. Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer. Int J Cancer. 2014;134:1683–1694.
  • Zhai L, Peabody J, Pang -Y-YS, et al. A novel candidate HPV vaccine: MS2 phage VLP displaying a tandem HPV L2 peptide offers similar protection in mice to gardasil-9. Antiviral Res. 2017;147:116–123.
  • Lynch AG, Tanzer F, Fraser MJ, et al. Use of the piggybac transposon to create HIV-1 gag transgenic insect cell lines for continuous VLP production. BMC Biotechnol. 2010;10:30.
  • Chang MO, Suzuki T, Yamamoto N, et al. HIV-1 gag-virus-like particles inhibit HIV-1 replication in dendritic cells and T cells through IFN-α-dependent upregulation of APOBEC3G and 3F. J Innate Immun. 2012;4:579–590.
  • Seldlik C, Dridi A, Deriaud E, et al. Intranasal delivery of recombinant parvovirus-like particles elicits cytotoxic T-cell and neutralizing antibody responses. J Virol. 1999;73:2739–2744.
  • Peabody J, Muttil P, Chackerian B, et al. Characterization of a spray-dried candidate HPV L2-VLP vaccine stored for multiple years at room temperature. Papillomavirus Res. 2017;3:116–120.
  • Lang R, Winter G, Vogt L, et al. Rational design of a stable, freeze-dried virus-like particle-based vaccine formulation. Drug Dev Ind Pharm. 2009;35:83–97. DOI:https://doi.org/10.1080/03639040802192806
  • Lan NT, Kim HJ, Han H-J, et al. Stability of virus-like particles of red-spotted grouper nervous necrosis virus in the aqueous state, and the vaccine potential of lyophilized particles. Biologicals. 2018;51:25–31.
  • Czyż M, Dembczyński R, Marecik R, et al. Freeze-drying of plant tissue containing HBV surface antigen for the oral vaccine against hepatitis B. Biomed Res Int. 2014;2014:485689.
  • Warzecha H, Mason HS, Lane C, et al. Oral immunogenicity of human papillomavirus-like particles expressed in potato. J Virol. 2003;77:8702–8711.
  • Janeway JCA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.
  • Sonnenberg GF, Hepworth MR. Functional interactions between innate lymphoid cells and adaptive immunity. Nat Rev Immunol. 2019;19:599–613.
  • Wculek SK, Cueto FJ, Mujal AM, et al. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20:7–24.
  • Cui J, Chen Y, Wang HY, et al. Mechanisms and pathways of innate immune activation and regulation in health and cancer. Hum Vaccines Immunother. 2014;10:3270–3285.
  • Gordon S. Pattern recognition receptors: doubling up for the innate immune response. Cell. 2002;111:927–930.
  • Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Front Immunol. 2014;5:461.
  • Zhu Y, An X, Zhang X, et al. STING: a master regulator in the cancer-immunity cycle. Mol Cancer. 2019;18:152.
  • Saxena M, Yeretssian G. NOD-like receptors: master regulators of inflammation and cancer. Front Immunol. 2014;5:327.
  • Yamamoto M, Takeda K. Current views of toll-like receptor signaling pathways. Gastroenterol. Res. Pract. 2010;1:240365.
  • Richert LE, Rynda-Apple A, Harmsen AL, et al. CD11c+ Cells primed with unrelated antigens facilitate an accelerated immune response to influenza virus in mice. Eur J Immunol. 2014;44:397–408. DOI:https://doi.org/10.1002/eji.201343587
  • Shepardson KM, Schwarz B, Larson K, et al. Induction of antiviral immune response through recognition of the repeating subunit pattern of viral capsids is toll-like receptor 2 dependent. MBio. 2017;8:e01356–17.
  • Allan RS, Waithman J, Bedoui S, et al. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity. 2006;25:153–162.
  • Morón VG, Rueda P, Sedlik C, et al. In vivo, dendritic cells can cross-present virus-like particles using an endosome-to-cytosol pathway. J Immunol. 2003;171:2242–2250.
  • Win SJ, Ward VK, Dunbar PR, et al. Cross-presentation of epitopes on virus-like particles via the MHC I receptor recycling pathway. Immunol Cell Biol. 2011;89:681–688.
  • Douglas T, Young M. Host-guest encapsulation of materials by assembled virus protein cages. Nature. 1998;393:152–155.
  • Strods A, Ose V, Bogans J, et al. Preparation by alkaline treatment and detailed characterisation of empty hepatitis B virus core particles for vaccine and gene therapy applications. Sci Rep. 2015;5:11639.
  • Li T-C, Takeda N, Miyamura T, et al. Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus. J Virol. 2005;79:12999–13006.
  • Hovlid ML, Lau JL, Breitenkamp K, et al. Encapsidated atom-transfer radical polymerization in Qβ virus-like nanoparticles. ACS Nano. 2014;8:8003–8014.
  • Lang S, Tan Z, Wu X, et al. Synthesis of carboxy-dimethylmaleic amide linked polymer conjugate based ultra-pH-sensitive nanoparticles for enhanced antitumor immunotherapy. ACS Macro Lett. 2020;9:1693–1699.
  • Klinman DM. Immunotherapeutic uses of CpG oligodeoxynucleotides. Nat Rev Immunol. 2004;4:249–259.
  • Storni T, Ruedl C, Schwarz K, et al. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic t cell responses in the absence of systemic side effects. J Immunol. 2004;172:1777–1785.
  • Mirsoian A, Bouchlaka MN, Sckisel GD, et al. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice. J Exp Med. 2014;211:2373–2383.
  • Bardel E, Doucet-Ladeveze R, Mathieu C, et al. Intradermal immunisation using the TLR3-ligand poly (I:C) as adjuvant induces mucosal antibody responses and protects against genital HSV-2 infection. NPJ Vaccines. 2016;1:16010.
  • Kadowaki N, Antonenko S, Liu Y-J. Distinct CpG DNA and polyinosic-polycytidylic acid double-stranded RNA, respectively, stimulate CD11c− type 2 dendritic cell precursors and CD11c+ dendritic cells to produce type I IFN. J Immunol. 2001;166:2291–2295.
  • Mohsen MO, Gomes AC, Vogel M, et al. Interaction of ciral capsid-derived virus-like particles (VLPs) with the innate immune system. Vaccines (Basel). 2018;6:37.
  • Cubas R, Zhang S, Kwon S, et al. Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes. J Immunother. 2009;32:118–128. DOI:https://doi.org/10.1097/CJI.0b013e31818f13c4
  • Bousso P. T-cell activation by dendritic cells in the lymph node: lessons from the movies. Nat Rev Immunol. 2008;8:675–684.
  • Derdak SV, Kueng HJ, Leb VM, et al. Direct stimulation of t lymphocytes by immunosomes: virus-like particles decorated with T cell receptor/CD3 ligands plus costimulatory molecules. Proc Natl Acad Sci USA. 2006;103:13144–13149.
  • Heider S, Dangerfield JA, Metzner C. Biomedical applications of glycosylphosphatidylinositol-anchored proteins. J Lipid Res. 2016;57:1778–1788. DOI:https://doi.org/10.1194/jlr.R070201.
  • Zhao L, Kopylov M, Potter CS, et al. Engineering the PP7 virus capsid as a peptide display platform. ACS Nano. 2019;13:4443–4454.
  • Fiedler JD, Higginson C, Hovlid ML, et al. Engineered mutations change the structure and stability of a virus-like particle. Biomacromolecules. 2012;13:2339–2348.
  • Davis SJ, van der Merwe PA. The kinetic-segregation model: TCR triggering and beyond. Nat Immunol. 2006;7:803–809.
  • Bakalar MH, Joffe AM, Schmid EM, et al. Size-dependent segregation controls macrophage phagocytosis of antibody-opsonized targets. Cell. 2018;174:131–142.
  • Qin Q, Yin Z, Wu X, et al. Valency and density matter: deciphering impacts of immunogen structures on immune responses against a tumor associated carbohydrate antigen using synthetic glycopolymers. Biomaterials. 2016;101:189–198.
  • Alam MM, Jarvis CM, Hincapie R, et al. Glycan-modified virus-like particles evoke helper type 1-like immune responses. ACS Nano. 2020;15:309–321.
  • Harty JT, Badovinac VP. Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol. 2008;8:107–119.
  • Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002;2:251–262.
  • Kaech SM, Cui W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol. 2012;12:749–761.
  • Grotzke JE, Sengupta D, Lu Q, et al. The ongoing saga of the mechanism(s) of MHC class I-restricted cross-presentation. Curr Opin Immunol. 2017;46:89–96.
  • Sede RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008;8:247–258.
  • Alloatti A, Rookhuizen DC, Joannas L, et al. Critical role for Sec22b-dependent cross-presentation in antitumor immunity. J Exp Med. 2017;214:2231–2241.
  • van Endert P, Montealegre S. MHC class I cross-presentation: stage lights on sec22b. Trends Immunol. 2017;38:618–621.
  • Wu SJ, Niknafs YS, Kim SH, et al. A critical analysis of the role of SNARE protein SEC22B in antigen cross-presentation. Cell Rep. 2017;19:2645–2656.
  • Houde M, Bertholet S, Gagnon E, et al. Phagosomes are competent organelles for antigen cross-presentation. Nature. 2003;425:402–406.
  • Yang J, Luo Y, Shibu MA, et al. Cell-penetrating peptides: efficient vectors for vaccine delivery. Curr Drug Deliv. 2019;16:430–443.
  • Appenzeller-Herzog C, Hauri H-P. The ER-golgi intermediate compartment (ERGIC): in search of its identity and function. J Cell Sci. 2006;119:2173–2183.
  • Serbian I, Visentin G, Blanchard N, et al. Sec22b regulates phagosomal maturation and antigen cross presentation by dendritic cells. Cell. 2011;147:1355–1368.
  • Gutiérrez-Martínez E, Planès R, Anselmi G, et al. Cross-presentation of cell-associated antigens by MHC class I in dendritic cell subsets. Front Immunol. 2015;6:363.
  • Leclerc D, Beauseigle D, Denis J, et al. Proteasome-independent major histocompatibility complex class i cross-presentation mediated by papaya mosaic virus-like particles leads to expansion of specific human T cells. J Virol. 2006;81:1319–1326.
  • Ruedl C, Storni T, Lechner F, et al. Cross-presentation of virus-like particles by skin-derived CD8- dendritic cells: a dispensable role for tap. Eur J Immunol. 2002;32:818–825.
  • Mant A, Chinnery F, Elliott T, et al. The pathway of cross-presentation is influenced by the particle size of phagocytosed antigen. Immunology. 2012;136:163–175.
  • Spice AJ, Aw R, Bracewell DG, et al. Synthesis and assembly of hepatitis B virus-like particles in a pichia pastoris cell-free system. Front Bioeng Biotechnol. 2020;8:72.
  • Ohlinger VF, Haas B, Meyers G, et al. Identification and characterization of the virus causing rabbit hemorrhagic disease. J Virol. 1990;64:3331–3336.
  • Parra F, Prieto M. Purification and characterization of a calicivirus as the causative agent of a lethal hemorrhagic disease in rabbits. J Virol. 1990;64:4013–4015.
  • Tamošiūnas PL, Petraitytė-Burneikienė R, Lasickienė R, et al. Generation of recombinant porcine parvovirus virus-like particles in saccharomyces cerevisiae and development of virus-specific monoclonal antibodies. J Immunol. 2014;2014:573531.
  • Kramer K, Al-Barwani F, Baird MA, et al. Functionalisation of virus-like particles enhances antitumour immune responses. J Immunol Res. 2019;2019:5364632.
  • Gonciarz-Swiatek M, Rechsteiner M. Proteasomes and antigen presentation: evidence that a KEKE motif does not promote presentation fo the class i epitope SIINFEKL. Mol Immunol. 2006;43:1993–2001.
  • Kapadia CH, Tian S, Perry JL, et al. Role of linker length and antigen density in nanoparticle peptide vaccine. ACS Omega. 2019;4:5547–5555.
  • Bijker MS, van Den Eeden SJF, Franken KL, et al. Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation. Eur J Immunol. 2008;38:1033–1042.
  • Craiu A, Akopian T, Goldberg A, et al. Two distinct proteolytic processes in the generation of a major histocompatibility complex class i-presented peptide. Proc Natl Acad Sci USA. 1997;94:10850–10855.
  • Rosalia RA, Quakkelaar ED, Redeker A, et al. Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation. Eur J Immunol. 2013;43:2554–2565.
  • Pierce SK, Liu W. The tipping points in the initiation of B cell signalling; how small changes make big differences. Nat Rev Immunol. 2010;10:767–777.
  • Mond JJ, Lees A, Snapper CM. T cell-independent antigens type 2. Annu Rev Immunol. 1995;13:655–692.
  • Metzger H. Transmembrane signaling: the joy of aggregation. J Immunol. 1992;149:1477–1487.
  • Bessa J, Schmitz N, Hinton HJ, et al. Efficient induction of mucosal and systemic immune responses by virus-like particles administered intranasally: implications for vaccine design. Eur J Immunol. 2008;38:114–126. DOI:https://doi.org/10.1002/eji.200636959
  • Minguet S, Dopfer EP, Schamel WW. Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor (BCR).Int Immunol. 2010;22(3):205–212. DOI:https://doi.org/10.1093/intimm/dxp129.
  • Dintzis HM, Dintzis RZ, Vogelstein B. Molecular determinants of immunogenicity: the immunon model of immune response. Proc Natl Acad Sci USA. 1976 ;73:3671–3675. DOI:https://doi.org/10.1073/pnas.73.10.3671
  • Sosnick TR, Benjamin DC, Novotny J, et al. Distances between the antigen-binding sites of three murine antibody subclasses measured using neutron and x-ray scattering. Biochemistry. 1992;31:1779–1786.
  • Dintzis RZ, Vogelstein B, Dintzis HM. Specific cellular stimulation in the primary immune response: experimental test of a quantized model. Proc Natl Acad Sci USA. 1982;79:884–888.
  • Bachmann MF, Hengartner H, Zinkernagel RM. T helper cell-independent neutralizing B cell response against vesicular stomatitis virus: role of antigen patterns in B cell induction? Eur J Immunol. 1995. 25:3445–3451. DOI:https://doi.org/10.1002/eji.1830251236.
  • Wu X, Mckay C, Pett C, et al. Synthesis and immunological evaluation of disaccharide bearing MUC-1 glycopeptide conjugates with virus-like particles. ACS Chem Biol. 2019;14(10):2176–2184. DOI:https://doi.org/10.1021/acschembio.9b00381. .
  • Jegerlehner A, Tissot A, Lechner F, et al. A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine. 2002;20:3104–3112.
  • Chackerian B, MR D, Schiller JT. 2008; Virus-like display of a neo-self antigen reverses B cell anergy in a B cell receptor transgenic mouse model. J Immunol. 180(9):5816–5825. DOI:https://doi.org/10.4049/jimmunol.180.9.5816.
  • Tolar P, Spillane KM. Force generation in B-cell synapsis: mechanisms coupling B-cell receptor binding to antigen internalization and affinity discrimination. Adv Immunol. 2014;123:69–100.
  • Fleire SJ, Goldman JP, Carrasco YR, et al. B cell ligand discrimination through a spreading and contraction response. Science. 2006;312:738–741.
  • Yin Z, Chowdhury S, McKay C, et al., Significant impact of immunogen design on the diversity of antibodies generated by carbohydrate-based anticancer vaccine. ACS Chem Biol. 10(10): 2364–2372. 2015. DOI:https://doi.org/10.1021/acschembio.5b00406.
  • Chan SK, Steinmetz NF. Isolation of cowpea mosaic virus-binding peptides. Biomacromolecules. 2021;22:3613–3623.
  • Garrod KR, Moreau HD, Garcia Z, et al. Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis. Cell Rep. 2012;2:1438–1447.
  • Mahnke YD, Brodie TM, Sallusto F, et al. The who’s who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013;43:2797–2809.
  • Mami-Chouaib F, Tartour E. Editorial: tissue resident memory T cells. Front Immunol. 2019;10:1018.
  • Jiang X, Clark RA, Liu L, et al. Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity. Nature. 2012;483:227–231.
  • Schenkel JM, Fraser KA, Vezys V, et al. Sensing and alarm function of resident memory CD8+ T cells. Nat Immunol. 2013;14:509–513.
  • Szabo PA, Miron M, Farber DL. Location: tissue resident memory T cells in mice and humans. Sci Immunol. 2019;4:eaas9673.
  • Lee Y-N, Lee Y-T, Kim M-C, et al. A novel vaccination strategy mediating the induction of lung-resident memory CD8 T cells confers heterosubtypic immunity against future pandemic influenza virus. J Immunol. 2016;196:2637–2645.
  • Schwarz B, Morabito KM, Ruckwardt TJ, et al. Virus like particles encapsidating respiratory syncytial virus M and M2 proteins induce robust T cell responses. ACS Biomater Sci Eng. 2016;2:2324–2332. DOI:https://doi.org/10.1021/acsbiomaterials.6b00532
  • Schenkel JM, Fraser KA, Beura LK, et al. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science. 2014;346:98–101.
  • Menares E, Gálvez-Cancino F, Cáceres-Morgado P, et al. Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells. Nat Commun. 2019;10:4401.
  • Ariotti S, Hogenbirk MA, Dijkgraaf FE, et al. Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert. Science. 2014;346:101–105.
  • Djenidi F, Adam J, Goubar A, et al. CD8+CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients. J Immunol. 2015;194:3475–3486.
  • Edwards J, Wilmott JS, Madore J, et al. CD103+ tumor-resident CD8+ T cells are associated with improved survival in immunotherapy-naïve melanoma patients and expanded significantly during anti-PD-1 treatment. Clin Cancer Res. 2018;24:3036–3045.
  • Caminschi I, Lahoud MH, Pizzola A, et al. Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development. Mucosal Immunol. 2019;12:403–412.
  • Lapuent D, Storcksdieck Genannt Bonsmann M, Maaske A, et al. IL-1ß as mucosal vaccine adjuvant: the specific induction of tissue-resident memory t cells improves the heterosubtypic immunity against influenza a viruses. Mucosal Immunol. 2018;11:1265–1278.
  • Wakim LM, Smith J, Caminschi I, et al. Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection. Mucosal Immunol. 2015;8:1060–1071.
  • Zepeda-Cervantes J, J R-J-Q, Vaca L. Interaction between virus-like particles (VLPs) and pattern recognition receptors (PRRs) from dendritic cells (DCs): towards better engineering of VLPs. Front Immunol. 2020;11:1100.
  • Knight FC, Wilson JT. Engineering vaccines for tissue-resident memory T cells. Adv Ther. 2021;4:2000230.
  • Grewal HM, Karlsen TH, Vetvik H, et al. Measurement of specific IgA in faecal extracts and intestinal lavage fluid for monitoring of mucosal immune responses. J Immunol Methods. 2000;239:53–62.
  • Braun M, Jandus C, Maurer P, et al. Virus-like particles induce robust human T-helper cell responses. Eur J Immunol. 2012;42:330–340.
  • Polonskaya Z, Deng S, Sarkar A, et al. T cells control the generation of nanomolar-affinity anti-glycan antibodies. J Clin Invest. 2017;127:1491–1504.
  • Slifka MK, Amanna IJ. Role of multivalency and antigenic threshold in generating protective antibody responses. Front Immunol. 2019;10:956.
  • Chackerian B, Peabody DS. Factors that govern the induction of long-lived antibody responses. Viruses. 2020;12:74.
  • Wu X, Ye J, DeLaitsch AT, et al. Chemoenzymatic synthesis of 9NHAc-GD2 antigen to overcome the hydrolytic instability of O-acetylated-GD2 for anticancer conjugate vaccine development. Angew Chem Int Ed. 2021;XX: Accepted Author Manuscript.
  • Wu X, McFall-Boegeman H, Rashidijahanabad Z, et al. Synthesis and immunological evaluation of the unnatural β-linked mucin-1 thomsen-friedenreich conjugate. Org Biomol Chem. 2021;19:2448–2455.
  • Dicker KT, Gurski LA, Pradhan-Bhatt S, et al. Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater. 2014;10:1558–1570.
  • Lauber DT, Fülöp A, Kovács T, et al. State of the art in vivo imaging techniques for laboratory animals. Lab Anim. 2017;51:465–478.
  • Martino ML, Crooke SN, Manchester M, et al. Single-point mutations in Qβ virus-like particles change binding to cells. Biomacromolecules. 2021;22:3332–3341.
  • Win SJ, McMillan DGG, Errington-Mais F, et al. Enhancing the immunogenicity of tumour lysate-loaded dendritic cell vaccines by conjugation to virus-like particles. Br J Cancer. 2012;106:92–98.
  • Braeden D, Lateef Z, Walker GF, et al. Virus-like particle vaccines: immunology and formulation for clinical translation. Expert Rev Vaccines. 2018;17:833–849.
  • Chang A. RBD-HBsAg conjugated virus-like particle vaccine protects rhesus macaques from SARS-CoV-2 challenge. Boston MA: Harvard Medical School; 2021.
  • Karpiński TM, Ozarowski M, Seremak-Mrozikiewicz A, et al. The 2020 race towards SARS-CoV-2 specific vaccines. Theranostics. 2021;11:1690–1702.

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