pH-triggered microparticles for peptide vaccination.
Improving vaccine delivery to human APCs is a way to increase the CTL response to vaccines. We report the use of a novel pH-triggered microparticle that exploits the ability of APCs to cross-present MHC I-restricted Ags that have been engulfed in the low pH environment of the phagosome. A model MHC class I-restricted peptide Ag from the influenza A matrix protein was encapsulated in spray-dried microparticles composed of dipalmitoylphosphatidylcholine and the pH-sensitive polymethacrylate Eudragit E100. Release of the peptide from the particle was triggered by a drop in pH to the acidity normally found in the phagosome. The particles were efficiently phagocytosed by human monocytes and dendritic cells with minimal cellular toxicity and no functional impairment. Encapsulation of the peptide in the microparticles resulted in efficient presentation of the peptide to CD8(+) T cells by human dendritic cells in vitro, and was superior to unencapsulated peptide or peptide encapsulated in an analogous pH-insensitive particle. Vaccination of human HLA-A*0201 transgenic mice with peptide encapsulated in pH-triggering microparticles resulted in priming of CTL responses. These microparticles can be modified to coencapsulate a range of adjuvants along with the Ag of interest. Encapsulation of MHC I epitopes in pH-triggered microparticles increases Ag presentation and may improve CD8(+) T cell priming to peptide vaccines against viruses and cancer.
Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Division of Pediatric Hematology/Oncology, Children's Hospital, Boston, MA 02115, USA.
W Nicholas
WN
Haining
Daniel G
DG
Anderson
Steven R
SR
Little
Michael S
MS
von Bergwelt-Baildon
Angelo A
AA
Cardoso
Pedro
P
Alves
Kostas
K
Kosmatopoulos
Lee M
LM
Nadler
Robert
R
Langer
Daniel S
DS
Kohane
Michael S
MS
von Berwelt-Baildon
D015060:1,2-Dipalmitoylphosphatidylcholine; D000179:Acrylates; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008863:Microspheres; D009000:Monocytes / Q000276:immunology; D010316:Particle Size; D010587:Phagocytosis / Q000502:physiology; D011108:Polymers; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*
D000179:Acrylates; D000956:Antigens, Viral; D004337:Drug Carriers; C477020:Eudragit E100; D015395:Histocompatibility Antigens Class I; D011108:Polymers; D022223:Vaccines, Subunit; D015060:1,2-Dipalmitoylphosphatidylcholine