A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4+ effector (CD44high CD62Llow) and memory (CD44high CD62Lhigh) T-cells in immunized mice

Nanomedicine. 2020 Oct:29:102257. doi: 10.1016/j.nano.2020.102257. Epub 2020 Jun 28.

Abstract

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP. Stimulation of mouse primary dendritic cells (DCs) with PLGA-rMOMP augmented endosome processing, induced Th1 cytokines (IL-6 and IL-12p40), and expression of MHC-II and co-stimulatory (CD40, CD80, and CD86) molecules. BALB/c mice immunized with PLGA-rMOMP produced enhanced CD4+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) phenotypes and functional antigen-specific serum IgG antibodies. In vivo biodistribution of PLGA-rMOMP revealed its localization within lymph nodes, suggesting migration from the injection site via DCs. Our data provide evidence that the PLGA (85:15) nanovaccine activates DCs and augments Chlamydia-specific rMOMP adaptive immune responses that are worthy of efficacy testing.

Keywords: Biodistribution; Chlamydia; Dendritic cells trafficking; PLGA [poly (D, L-lactide-co-glycolide)] nanoparticles; T-cells and antibody responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / genetics*
  • Adaptive Immunity / immunology
  • Animals
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / immunology
  • CD4 Antigens / chemistry
  • CD4 Antigens / immunology
  • Chlamydia / genetics
  • Chlamydia / immunology
  • Chlamydia / pathogenicity
  • Dendritic Cells / immunology
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Hyaluronan Receptors / chemistry
  • Hyaluronan Receptors / immunology
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-12 Subunit p40 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • L-Selectin / chemistry
  • L-Selectin / immunology
  • Mice
  • Nanoparticles / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / immunology
  • T-Lymphocytes / immunology
  • Vaccines / genetics
  • Vaccines / immunology*

Substances

  • Bacterial Outer Membrane Proteins
  • CD4 Antigens
  • Histocompatibility Antigens Class II
  • Hyaluronan Receptors
  • Interleukin-12 Subunit p40
  • Interleukin-6
  • Vaccines
  • L-Selectin
  • OMPA outer membrane proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer