All Title Author
Keywords Abstract

PLOS ONE  2012 

Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine

DOI: 10.1371/journal.pone.0031472

Full-Text   Cite this paper   Add to My Lib

Abstract:

The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.

References

[1]  Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, et al. (2007) Vivax malaria: neglected and not benign. Am J Trop Med Hyg 77: 79–87.
[2]  Mueller I, Galinski MR, Baird JK, Carlton JM, Kochar DK, et al. (2009) Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis 9: 555–566.
[3]  Vogel G (2010) Infectious disease. New map illustrates risk from the ‘other’ malaria. Science 329: 618.
[4]  Yadava A, Sattabongkot J, Washington MA, Ware LA, Majam V, et al. (2007) A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites. Infect Immun 75: 1177–1185.
[5]  Bell BA, Wood JF, Bansal R, Ragab H, Cargo J 3rd, et al. (2009) Process development for the production of an E. coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax. Vaccine 27: 1448–1453.
[6]  Ballou WR (2009) The development of the RTS,S malaria vaccine candidate: challenges and lessons. Parasite Immunol 31: 492–500.
[7]  Jegerlehner A, Storni T, Lipowsky G, Schmid M, Pumpens P, et al. (2002) Regulation of IgG antibody responses by epitope density and CD21-mediated costimulation. Eur J Immunol 32: 3305–3314.
[8]  Liu W, Chen YH (2005) High epitope density in a single protein molecule significantly enhances antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric proteins. Eur J Immunol 35: 505–514.
[9]  Kazzaz J, Singh M, Ugozzoli M, Chesko J, Soenawan E, et al. (2006) Encapsulation of the immune potentiators MPL and RC529 in PLG microparticles enhances their potency. J Control Release 110: 566–573.
[10]  Reddy ST, van der Vlies AJ, Simeoni E, Angeli V, Randolph GJ, et al. (2007) Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat Biotechnol 25: 1159–1164.
[11]  Ataman-Onal Y, Munier S, Ganee A, Terrat C, Durand PY, et al. (2006) Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models. J Control Release 112: 175–185.
[12]  Cui Z, Patel J, Tuzova M, Ray P, Phillips R, et al. (2004) Strong T cell type-1 immune responses to HIV-1 Tat (1-72) protein-coated nanoparticles. Vaccine 22: 2631–2640.
[13]  Fifis T, Gamvrellis A, Crimeen-Irwin B, Pietersz GA, Li J, et al. (2004) Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol 173: 3148–3154.
[14]  Otten G, Schaefer M, Greer C, Calderon-Cacia M, Coit D, et al. (2003) Induction of broad and potent anti-human immunodeficiency virus immune responses in rhesus macaques by priming with a DNA vaccine and boosting with protein-adsorbed polylactide coglycolide microparticles. J Virol 77: 6087–6092.
[15]  Zhang XQ, Dahle CE, Weiner GJ, Salem AK (2007) A comparative study of the antigen-specific immune response induced by co-delivery of CpG ODN and antigen using fusion molecules or biodegradable microparticles. J Pharm Sci 96: 3283–3292.
[16]  Demento SL, Bonafe N, Cui W, Kaech SM, Caplan MJ, et al. (2010) TLR9-targeted biodegradable nanoparticles as immunization vectors protect against West Nile encephalitis. J Immunol 185: 2989–2997.
[17]  Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, et al. (2011) Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470: 543–547.
[18]  Bershteyn A, Chaparro J, Yau R, Kim M, Reinherz E, et al. (2008) Polymer-supported lipid shells, onions, and flowers. Soft Matter 4: 1787–1791.
[19]  Bershteyn A, Hanson MC, Crespo MP, Moon JJ, Li AV, et al. (2011) Robust IgG responses to nanograms of antigen using a biomimetic lipid-coated particle vaccine. J Control Release. In press.
[20]  Sharp FA, Ruane D, Claass B, Creagh E, Harris J, et al. (2009) Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc Natl Acad Sci U S A 106: 870–875.
[21]  Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, et al. (2009) Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27: 3013–3021.
[22]  Yue Y, Xu W, Hu L, Jiang Z, Xiong S (2009) Enhanced resistance to coxsackievirus B3-induced myocarditis by intranasal co-immunization of lymphotactin gene encapsulated in chitosan particle. Virology 386: 438–447.
[23]  McHeyzer-Williams LJ, McHeyzer-Williams MG (2005) Antigen-specific memory B cell development. Annu Rev Immunol 23: 487–513.
[24]  Nutt SL, Tarlinton DM (2011) Germinal center B and follicular helper T cells: siblings, cousins or just good friends? Nat Immunol 131: 472–477.
[25]  Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, et al. (2009) Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325: 1006–1010.
[26]  Charoenvit Y, Collins WE, Jones TR, Millet P, Yuan L, et al. (1991) Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence. Science 251: 668–671.
[27]  Jones TR, Yuan LF, Marwoto HA, Gordon DM, Wirtz RA, et al. (1992) Low immunogenicity of a Plasmodium vivax circumsporozoite protein epitope bound by a protective monoclonal antibody. Am J Trop Med Hyg 47: 837–843.
[28]  Udhayakumar V, Saekhou A, Fang S, Jue D, Wohlhueter RM, et al. (1998) Immunogenicity of Plasmodium falciparum and Plasmodium vivax circumsporozoite protein repeat multiple antigen constructs (MAC). Vaccine 16: 982–988.
[29]  Kovacsovics-Bankowski M, Clark K, Benacerraf B, Rock KL (1993) Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A 90: 4942–4946.
[30]  Moon JJ, Suh H, Bershteyn A, Stephan MT, Liu H, et al. (2011) Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat Mater 10: 243–251.
[31]  Moon JJ, Suh H, Li AV, Ockenhouse CF, Yadava A, 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. 10.1073/pnas.1112648109.
[32]  Vanderberg JP, Frevert U (2004) Intravital microscopy demonstrating antibody-mediated immobilisation of Plasmodium berghei sporozoites injected into skin by mosquitoes. Int J Parasitol 34: 991–996.
[33]  Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, et al. (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192: 1545–1552.
[34]  Liu H, Kwong B, Irvine DJ (2011) Membrane anchored immunostimulatory oligonucleotides for in vivo cell modification and localized immunotherapy. Angew Chem Int Ed Engl 50: 7052–7055.
[35]  Jewell CM, Bustamante Lopez SC, Irvine DJ (2011) In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. Proc Natl Acad Sci U S A.

Full-Text

comments powered by Disqus