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Nano-Particulate Platforms for Vaccine Delivery to Enhance Antigen-Specific CD8+ T-Cell Response

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Vaccine Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2412))

Abstract

Vaccines remain the most effective way to protect populations against deathly infectious diseases. Several disadvantages associated with the traditional vaccines that use whole pathogens have led to the development of alternative strategies including the use of recombinant subunit vaccines. Subunit vaccines are, in general, safer than whole pathogens but tend to be less immunogenic due to the lack of molecular cues that are typically found on whole pathogens. To enhance immunogenicity, the subunit antigen  can be administered with adjuvants that stimulate the innate immune system as a means to steer the quality and magnitude of the adaptive immune response. Novel classes of adjuvants are formulated using particle-based platforms such as virus-like particles, liposomes, and polymeric nanoparticles. These particle-based systems present antigens in ways reminiscent of whole pathogens. Such platforms offer several advantages that include co-delivery of antigen along with innate immune stimulators in a highly immunogenic format. Here we describe our recent efforts to synthesize, characterize, and validate two promising nanoparticle-based delivery systems and demonstrate their potential to induce antigen-specific CD8+ T cell responses, essential in clearing infection with intracellular pathogens, such as viruses and bacteria, and eradicating tumors.

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References

  1. Black M, Trent A, Tirrell M, Olive C (2010) Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines 9:157–173

    Article  CAS  Google Scholar 

  2. Fischer NO et al (2013) Colocalized delivery of adjuvant and antigen using nanolipoprotein particles enhances the immune response to recombinant antigens. J Am Chem Soc 135:2044–2047

    Article  CAS  Google Scholar 

  3. Shae D et al (2020) Co-delivery of peptide neoantigens and stimulator of interferon genes agonists enhances response to cancer vaccines. ACS Nano 14:9904–9916

    Article  CAS  Google Scholar 

  4. Wilson JT et al (2015) Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles. AAPS J 17:358–369

    Article  CAS  Google Scholar 

  5. Bookstaver ML, Tsai SJ, Bromberg JS, Jewell CM (2018) Improving vaccine and immunotherapy design using biomaterials. Trends Immunol 39:135–150

    Article  CAS  Google Scholar 

  6. Wilson JT et al (2013) pH-responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. ACS Nano 7:3912–3925

    Article  CAS  Google Scholar 

  7. Reed SG, Bertholet S, Coler RN, Friede M (2009) New horizons in adjuvants for vaccine development. Trends Immunol 30:23–32

    Article  CAS  Google Scholar 

  8. Stanley M (2017) Tumour virus vaccines: hepatitis B virus and human papillomavirus. Philos Trans R Soc Lond B Biol Sci 372(1732):20160268

    Article  Google Scholar 

  9. Chackerian B (2007) Virus-like particles-flexible platforms for vaccine development. Expert Rev Vaccines 6:381–390

    Article  CAS  Google Scholar 

  10. Brune KD et al (2016) Plug-and-display: decoration of virus-like particles via isopeptide bonds for modular immunization. Sci Rep 6:19234

    Article  CAS  Google Scholar 

  11. Sharma J et al (2020) A self-adjuvanted, modular, antigenic VLP for rapid response to influenza virus variability. ACS Appl Mater Interfaces 12:18211–18224

    Article  CAS  Google Scholar 

  12. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796

    Article  CAS  Google Scholar 

  13. Hua ZL, Hou BD (2013) TLR signaling in B-cell development and activation. Cell Mol Immunol 10:103–106

    Article  CAS  Google Scholar 

  14. Zabel F, Kundig TM, Bachmann MF (2013) Virus-induced humoral immunity: on how B cell responses are initiated. Curr Opin Virol 3:357–362

    Article  CAS  Google Scholar 

  15. Patterson DP, Rynda-Apple A, Harmsen AL, Harmsen AG, Douglas T (2013) Biomimetic antigenic nanoparticles elicit controlled protective immune response to influenza. ACS Nano 7:3036–3044

    Article  CAS  Google Scholar 

  16. Schwarz B et al (2016) Viruslike particles encapsidating respiratory syncytial virus M and M2 proteins induce robust T cell responses. ACS Biomater Sci Eng 2:2324–2332

    Article  CAS  Google Scholar 

  17. Rynda-Apple A, Patterson DP, Douglas T (2014) Virus-like particles as antigenic nanomaterials for inducing protective immune responses in the lung. Nanomedicine 9:1857–1868

    Article  CAS  Google Scholar 

  18. Pumpens P, Grens E (2001) HBV core particles as a carrier for B cell/T cell epitopes. Intervirology 44:98–114

    Article  CAS  Google Scholar 

  19. Schafer K et al (1999) Immune response to human papillomavirus 16 L1E7 chimeric virus-like particles: induction of cytotoxic T cells and specific tumor protection. Int J Cancer 81:881–888

    Article  CAS  Google Scholar 

  20. Ruedl C et al (2005) Virus-like particles as carriers for T-cell epitopes: limited inhibition of T-cell priming by carrier-specific antibodies. J Virol 79:717–724

    Article  CAS  Google Scholar 

  21. Joffre OP, Segura E, Savina A, Amigorena S (2012) Cross-presentation by dendritic cells. Nat Rev Immunol 12:557–569

    Article  CAS  Google Scholar 

  22. Gause KT et al (2017) Immunological principles guiding the rational design of particles for vaccine delivery. ACS Nano 11:54–68

    Article  CAS  Google Scholar 

  23. Irvine DJ, Swartz MA, Szeto GL (2013) Engineering synthetic vaccines using cues from natural immunity. Nat Mater 12:978–990

    Article  CAS  Google Scholar 

  24. Canton I, Battaglia G (2012) Endocytosis at the nanoscale. Chem Soc Rev 41:2718–2739

    Article  CAS  Google Scholar 

  25. Graham DB et al (2010) ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling. Blood 116:3208–3218

    Article  CAS  Google Scholar 

  26. Wan Y, Moyle PM, Toth I (2015) Endosome escape strategies for improving the efficacy of oligonucleotide delivery systems. Curr Med Chem 22:3326–3346

    Article  CAS  Google Scholar 

  27. Sharma J, Uchida M, Miettinen HM, Douglas T (2017) Modular interior loading and exterior decoration of a virus-like particle. Nanoscale 9:10420–10430

    Article  CAS  Google Scholar 

  28. Schwarz B et al (2015) Symmetry controlled, genetic presentation of bioactive proteins on the P22 virus-like particle using an external decoration protein. Acs Nano 9:9134–9147

    Article  CAS  Google Scholar 

  29. Knight FC et al (2019) Mucosal immunization with a pH-responsive nanoparticle vaccine induces protective CD8(+) lung-resident memory T cells. ACS Nano 13:10939–10960

    Article  CAS  Google Scholar 

  30. O’Neil A, Reichhardt C, Johnson B, Prevelige PE, Douglas T (2011) Genetically programmed in vivo packaging of protein cargo and its controlled release from bacteriophage P22. Angew Chem Int Edit 50:7425–7428

    Article  Google Scholar 

  31. Padilla-Meier GP et al (2012) Unraveling the role of the C-terminal helix turn helix of the coat-binding domain of bacteriophage P22 scaffolding protein. J Biol Chem 287:33766–33780

    Article  CAS  Google Scholar 

  32. Botstein D, Waddell CH, King J (1973) Mechanism of head assembly and DNA encapsulation in Salmonella phage p22. I. Genes, proteins, structures and DNA maturation. J Mol Biol 80:669–695

    Article  CAS  Google Scholar 

  33. McCoy K, Douglas T (2018) In vivo packaging of protein cargo inside of virus-like particle P22. Methods Mol Biol 1776:295–302

    Article  CAS  Google Scholar 

  34. Sharma J, Douglas T (2020) Tuning the catalytic properties of P22 nanoreactors through compositional control. Nanoscale 12:336–346

    Article  CAS  Google Scholar 

  35. Waghwani HK et al (2020) Virus-like particles (VLPs) as a platform for hierarchical compartmentalization. Biomacromolecules 21:2060–2072

    Article  CAS  Google Scholar 

  36. Prevelige PE Jr, Thomas D, King J (1988) Scaffolding protein regulates the polymerization of P22 coat subunits into icosahedral shells in vitro. J Mol Biol 202:743–757

    Article  CAS  Google Scholar 

  37. Evans BC et al (2013) Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. J Vis Exp e50166. https://doi.org/10.3791/50166

  38. Kumar A et al (2020) Heterotypic immunity against vaccinia virus in an HLA-B*07:02 transgenic mousepox infection model. Sci Rep 10:13167

    Article  CAS  Google Scholar 

  39. Brito LA, Singh M (2011) Acceptable levels of endotoxin in vaccine formulations during preclinical research. J Pharm Sci 100:34–37

    Article  CAS  Google Scholar 

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Acknowledgments

SJ is a Research Career Scientist supported by IK6 BX004595 from the Department of Veterans Affairs. Supported by Vanderbilt University Discovery Grants Programs (JWT, SJ) as well as VA Merit Award (BX001444: SJ); NIH Contracts (AI040079: SJ), and Research (AI042284, HL121139: SJ; AI121626: JWT), Core (CA068485, DK058404), and Center (CA068485) grants; NSF research (CBET-1554623: JWT) and Fellowship DGE-1445197 and DGE-1937963: CSC) grants; Stand Up To Cancer Innovative Research Grant (SU2C-AACR-IRG 20-17: JWT)—a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research—the scientific partner of SU2C—and Human Frontier Science Program (HFSP 4124801: TD).

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Correspondence to Sebastian Joyce .

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Sharma, J., Carson, C.S., Douglas, T., Wilson, J.T., Joyce, S. (2022). Nano-Particulate Platforms for Vaccine Delivery to Enhance Antigen-Specific CD8+ T-Cell Response. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 2412. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1892-9_19

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  • DOI: https://doi.org/10.1007/978-1-0716-1892-9_19

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-1891-2

  • Online ISBN: 978-1-0716-1892-9

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