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

Shailendra B. Tallapaka, Bala V.K. Karuturi, Pravin Yeapuri, Stephen M. Curran, Yogesh A. Sonawane, Joy A. Phillips, D. David Smith, Sam D. Sanderson, Joseph A. Vetro

Research output: Contribution to journalArticle

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 naïve 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.

Original languageEnglish (US)
Pages (from-to)242-257
Number of pages16
JournalInternational Journal of Pharmaceutics
Volume565
DOIs
Publication statusPublished - Jun 30 2019

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Keywords

  • CD88
  • Complement-derived immunostimulant
  • Dendritic cell targeting
  • Host-derived immunostimulant
  • Mucosal vaccine
  • Nanoparticle
  • Targeted vaccines
  • Vaccine delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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