In vivo characterization of the physicochemical properties of polymer-linked TLR agonists that enhance vaccine immunogenicity

. 2015 Nov ; 33 (11) : 1201-10. [epub] 20151026

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid26501954

Grantová podpora
Z99 AI999999 Intramural NIH HHS - United States
K22 AI108628 NIAID NIH HHS - United States
C552/A17720 Cancer Research UK - United Kingdom
T32 GM145449 NIGMS NIH HHS - United States
17720 Cancer Research UK - United Kingdom
T32 GM007171 NIGMS NIH HHS - United States

The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer-TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer-TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer-TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer-TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.

Komentář v

PubMed

Zobrazit více v PubMed

Plotkin SA. Correlates of protection induced by vaccination. Clinical and vaccine immunology: CVI. 2010;17:1055–1065. PubMed PMC

Epstein JE, et al. Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity. Science. 2011;334:475–480. PubMed

Andersen P, Woodworth JS. Tuberculosis vaccines–rethinking the current paradigm. Trends Immunol. 2014;35:387–395. PubMed

Arens R, van Hall T, van der Burg SH, Ossendorp F, Melief CJ. Prospects of combinatorial synthetic peptide vaccine-based immunotherapy against cancer. Seminars in immunology. 2013;25:182–190. PubMed

Guy B. The perfect mix: recent progress in adjuvant research. Nature reviews Microbiology. 2007;5:505–517. PubMed

Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–995. PubMed

Nordly P, Madsen HB, Nielsen HM, Foged C. Status and future prospects of lipid-based particulate delivery systems as vaccine adjuvants and their combination with immunostimulators. Expert opinion on drug delivery. 2009;6:657–672. PubMed

Brito LA, O’Hagan DT. Designing and building the next generation of improved vaccine adjuvants. Journal of controlled release: official journal of the Controlled Release Society. 2014;190C:563–579. PubMed

Fox CB, et al. TLR4 ligand formulation causes distinct effects on antigen-specific cell-mediated and humoral immune responses. Vaccine. 2013;31:5848–5855. PubMed

Wille-Reece U, et al. HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci U S A. 2005;102:15190–15194. PubMed PMC

Shukla NM, et al. Toward self-adjuvanting subunit vaccines: model peptide and protein antigens incorporating covalently bound toll-like receptor-7 agonistic imidazoquinolines. Bioorg Med Chem Lett. 2011;21:3232–3236. PubMed PMC

Wu CC, et al. Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand. Proc Natl Acad Sci U S A. 2007;104:3990–3995. PubMed PMC

Kasturi SP, et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature. 2011;470:543–547. PubMed PMC

Jewell CM, Lopez SC, Irvine DJ. In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. Proc Natl Acad Sci U S A. 2011;108:15745–15750. PubMed PMC

Ilyinskii PO, et al. Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release. Vaccine. 2014;32:2882–2895. PubMed PMC

Moon JJ, et al. Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc Natl Acad Sci U S A. 2012;109:1080–1085. PubMed PMC

Smirnov D, Schmidt JJ, Capecchi JT, Wightman PD. Vaccine adjuvant activity of 3M-052: an imidazoquinoline designed for local activity without systemic cytokine induction. Vaccine. 2011;29:5434–5442. PubMed

Liu H, et al. Structure-based programming of lymph-node targeting in molecular vaccines. Nature. 2014;507:519–522. PubMed PMC

Wu TY, et al. Rational design of small molecules as vaccine adjuvants. Sci Transl Med. 2014;6:263ra160. PubMed

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

Manolova V, et al. Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol. 2008;38:1404–1413. PubMed

Reddy ST, Rehor A, Schmoekel HG, Hubbell JA, Swartz MA. In vivo targeting of dendritic cells in lymph nodes with poly(propylene sulfide) nanoparticles. Journal of controlled release: official journal of the Controlled Release Society. 2006;112:26–34. PubMed

Kourtis IC, et al. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. PLoS One. 2013;8:e61646. PubMed PMC

Gorden KB, et al. Synthetic TLR Agonists reveal functional differences between human TLR7 and TLR8. Journal of Immunology. 2005;174:1259–1268. PubMed

Oh JZ, Kurche JS, Burchill MA, Kedl RM. TLR7 enables cross-presentation by multiple dendritic cell subsets through a type I IFN-dependent pathway. Blood. 2011;118:3028–3038. PubMed PMC

Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010;33:492–503. PubMed PMC

Gerster JF, et al. Synthesis and structure-activity-relationships of 1H-imidazo[4,5-c]quinolines that induce interferon production. J Med Chem. 2005;48:3481–3491. PubMed

A AG, Tyring SK, Rosen T. Beyond a decade of 5% imiquimod topical therapy. Journal of drugs in dermatology: JDD. 2009;8:467–474. PubMed

Savage P, et al. A phase I clinical trial of imiquimod, an oral interferon inducer, administered daily. British journal of cancer. 1996;74:1482–1486. PubMed PMC

Pockros PJ, et al. Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies. Journal of hepatology. 2007;47:174–182. PubMed

Seymour LW, et al. Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin. J Clin Oncol. 2002;20:1668–1676. PubMed

Liu XM, Miller SC, Wang D. Beyond oncology–application of HPMA copolymers in non-cancerous diseases. Advanced drug delivery reviews. 2010;62:258–271. PubMed PMC

Seymour LW, Duncan R, Strohalm J, Kopecek J. Effect of Molecular-Weight (Mbarw) of N-(2-Hydroxypropyl)Methacrylamide Copolymers on Body Distribution and Rate of Excretion after Subcutaneous, Intraperitoneal, and Intravenous Administration to Rats. J Biomed Mater Res. 1987;21:1341–1358. PubMed

Sharp FA, et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc Natl Acad Sci U S A. 2009;106:870–875. PubMed PMC

Russo C, et al. Small molecule Toll-like receptor 7 agonists localize to the MHC class II loading compartment of human plasmacytoid dendritic cells. Blood. 2011;117:5683–5691. PubMed

Ryu KA, Stutts L, Tom JK, Mancini RJ, Esser-Kahn AP. Stimulation of Innate Immune Cells by Light-Activated TLR7/8 Agonists. Journal of the American Chemical Society. 2014;136:10823–10825. PubMed PMC

Shakya AK, Holmdahl R, Nandakumar KS, Kumar A. Characterization of chemically defined poly-N-isopropylacrylamide based copolymeric adjuvants. Vaccine. 2013;31:3519–3527. PubMed

Shi HS, et al. Novel vaccine adjuvant LPS-Hydrogel for truncated basic fibroblast growth factor to induce antitumor immunity. Carbohydr Polym. 2012;89:1101–1109. PubMed

Chou HY, et al. Hydrogel-delivered GM-CSF overcomes nonresponsiveness to hepatitis B vaccine through the recruitment and activation of dendritic cells. J Immunol. 2010;185:5468–5475. PubMed

Blander JM, Medzhitov R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature. 2006;440:808–812. PubMed

Nair-Gupta P, et al. TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell. 2014;158:506–521. PubMed PMC

Jing P, Rudra JS, Herr AB, Collier JH. Self-assembling peptide-polymer hydrogels designed from the coiled coil region of fibrin. Biomacromolecules. 2008;9:2438–2446. PubMed PMC

Pechar M, Pola R. The coiled coil motif in polymer drug delivery systems. Biotechnology advances. 2013;31:90–96. PubMed

Kastenmuller K, et al. Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets. J Clin Invest. 2011;121:1782–1796. PubMed PMC

Vecchi S, et al. Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2014;87:310–317. PubMed

Scott EA, et al. Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes. Biomaterials. 2012;33:6211–6219. PubMed

Liu H, Kwong B, Irvine DJ. Membrane anchored immunostimulatory oligonucleotides for in vivo cell modification and localized immunotherapy. Angewandte Chemie. 2011;50:7052–7055. PubMed PMC

Krieg AM, Stein CA. Phosphorothioate oligodeoxynucleotides: antisense or anti-protein? Antisense research and development. 1995;5:241. PubMed

Lahoud MH, et al. DEC-205 is a cell surface receptor for CpG oligonucleotides. Proc Natl Acad Sci U S A. 2012;109:16270–16275. PubMed PMC

de Titta A, et al. Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose. Proc Natl Acad Sci U S A. 2013;110:19902–19907. PubMed PMC

Shukla NM, Malladi SS, Mutz CA, Balakrishna R, David SA. Structure-activity relationships in human toll-like receptor 7-active imidazoquinoline analogues. J Med Chem. 2010;53:4450–4465. PubMed PMC

Hruby M, et al. New bioerodable thermoresponsive polymers for possible radiotherapeutic applications. Journal of controlled release: official journal of the Controlled Release Society. 2007;119:25–33. PubMed

Subr V, Ulbrich K. Synthesis and properties of new N-(2-hydroxypropyl)-methacrylamide copolymers containing thiazolidine-2-thione reactive groups. React Funct Polym. 2006;66:1525–1538.

Skeiky YA, et al. Protective efficacy of a tandemly linked, multi-subunit recombinant leishmanial vaccine (Leish-111f) formulated in MPL adjuvant. Vaccine. 2002;20:3292–3303. PubMed

Gerner MY, Kastenmuller W, Ifrim I, Kabat J, Germain RN. Histo-cytometry: a method for highly multiplex quantitative tissue imaging analysis applied to dendritic cell subset microanatomy in lymph nodes. Immunity. 2012;37:364–376. PubMed PMC

Quinn KM, et al. Comparative analysis of the magnitude, quality, phenotype, and protective capacity of simian immunodeficiency virus gag-specific CD8+ T cells following human-, simian-, and chimpanzee-derived recombinant adenoviral vector immunization. J Immunol. 2013;190:2720–2735. PubMed PMC

Darrah PA, et al. Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nature medicine. 2007;13:843–850. PubMed

Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008;8:247–258. PubMed

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Synthesis and Structure Optimization of Star Copolymers as Tunable Macromolecular Carriers for Minimal Immunogen Vaccine Delivery

. 2024 Aug 21 ; 35 (8) : 1218-1232. [epub] 20240731

Recent advances on smart glycoconjugate vaccines in infections and cancer

. 2022 Jul ; 289 (14) : 4251-4303. [epub] 20210601

Fab-dimerized glycan-reactive antibodies are a structural category of natural antibodies

. 2021 May 27 ; 184 (11) : 2955-2972.e25. [epub] 20210520

Nanomaterials and Nanotechnology-Associated Innovations against Viral Infections with a Focus on Coronaviruses

. 2020 May 31 ; 10 (6) : . [epub] 20200531

Design of a broadly reactive Lyme disease vaccine

. 2020 ; 5 (1) : 33. [epub] 20200501

Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens

. 2020 Mar ; 38 (3) : 320-332. [epub] 20200113

Induction of anti-cancer T cell immunity by in situ vaccination using systemically administered nanomedicines

. 2019 Sep 10 ; 459 () : 192-203. [epub] 20190608

Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates

. 2019 Jun ; 17 (6) : e3000328. [epub] 20190617

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...