@article{f3680cb43ffe46eaa4d54bb3203c6e42,
title = "Surface conjugation of EP67 to biodegradable nanoparticles increases the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccine after respiratory immunization and subsequent T-cell-mediated protection against respiratory infection",
abstract = " Encapsulation of protein vaccines in biodegradable nanoparticles (NP)increases T-cell expansion after mucosal immunization but requires incorporating a suitable immunostimulant to increase long-lived memory T-cells. EP67 is a clinically viable, host-derived peptide agonist of the C5a receptor that selectively activates antigen presenting cells over neutrophils. We previously found that encapsulating EP67-conjugated CTL peptide vaccines in NP increases long-lived memory subsets of CTL after respiratory immunization. Thus, we hypothesized that alternatively conjugating EP67 to the NP surface can increase long-lived mucosal and systemic memory T-cells generated by encapsulated protein vaccines. We found that respiratory immunization of na{\"i}ve female C57BL/6 mice with LPS-free ovalbumin (OVA)encapsulated in PLGA 50:50 NP (∼380 nm diameter)surface-conjugated with ∼0.1 wt% EP67 through 2 kDa PEG linkers (i)increased T-cell expansion and long-lived memory subsets of OVA 323-339 -specific CD4 + and OVA 257-264 -specific CD8a + T-cells in the lungs (CD44 HI /CD127/KLRG1)and spleen (CD44 HI /CD127/KLRG1/CD62L)and (ii)decreased peak CFU of OVA-expressing L. monocytogenes (LM-OVA)in the lungs, liver, and spleen after respiratory challenge vs. encapsulation in unmodified NP. Thus, conjugating EP67 to the NP surface is one approach to increase the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccines after respiratory immunization.",
keywords = "CD88, Complement-derived immunostimulant, Dendritic cell targeting, Host-derived immunostimulant, Mucosal vaccine, Nanoparticle, Targeted vaccines, Vaccine delivery",
author = "Tallapaka, {Shailendra B.} and Karuturi, {Bala V.K.} and Pravin Yeapuri and Curran, {Stephen M.} and Sonawane, {Yogesh A.} and Phillips, {Joy A.} and {David Smith}, D. and Sam Sanderson and Vetro, {Joseph A.}",
note = "Funding Information: This work was supported by NIH 1R01AI121050/NIAID (JAV), NIH R41AI094710/NIAID (SDS), NIH COBRE 2P20GM103480/NCRR (Nebraska Center for Nanomedicine), the UNMC Edna Ittner Research Fund (JAV), and UNMC Predoctoral Fellowships (SBT, VKK). We thank Dr. Clifford Harding for the murine T-cell hybridomas, Dr. John Harty for LM-OVA, Victoria Smith M.S. and Dr. Philip Hexley in the UNMC Flow Cytometry Facility, Dr. Laurey Steinke in the UNMC Protein Structure Core Facility, and the NIH Tetramer Core Facility (Contract HHSN272201300006C)for OVA tetramers. The UNMC Flow Cytometry Research Facility and Protein Structure Core Facility is managed through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI)and The Fred and Pamela Buffet Cancer Center's National Cancer Institute Cancer Support Grant. Funding Information: This work was supported by NIH 1R01AI121050/NIAID (JAV), NIH R41AI094710/NIAID (SDS), NIH COBRE 2P20GM103480/NCRR (Nebraska Center for Nanomedicine), the UNMC Edna Ittner Research Fund (JAV), and UNMC Predoctoral Fellowships (SBT, VKK). We thank Dr. Clifford Harding for the murine T-cell hybridomas, Dr. John Harty for LM-OVA, Victoria Smith M.S. and Dr. Philip Hexley in the UNMC Flow Cytometry Facility, Dr. Laurey Steinke in the UNMC Protein Structure Core Facility, and the NIH Tetramer Core Facility (Contract HHSN272201300006C) for OVA tetramers. The UNMC Flow Cytometry Research Facility and Protein Structure Core Facility is managed through the Office of the Vice Chancellor for Research and supported by state funds from the Nebraska Research Initiative (NRI) and The Fred and Pamela Buffet Cancer Center{\textquoteright}s National Cancer Institute Cancer Support Grant. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2019",
month = jun,
day = "30",
doi = "10.1016/j.ijpharm.2019.05.012",
language = "English (US)",
volume = "565",
pages = "242--257",
journal = "International journal of pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
}