Characterization of immunogenicity of avian influenza antigens encapsulated in PLGA nanoparticles following mucosal and subcutaneous delivery in chickens

PLoS One. 2018 Nov 1;13(11):e0206324. doi: 10.1371/journal.pone.0206324. eCollection 2018.

Abstract

Mucosal vaccine delivery systems have paramount importance for the induction of mucosal antibody responses. Two studies were conducted to evaluate immunogenicity of inactivated AIV antigens encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). In the first study, seven groups of specific pathogen free (SPF) layer-type chickens were immunized subcutaneously at 7-days of age with different vaccine formulations followed by booster vaccinations two weeks later. Immune responses were profiled by measuring antibody (Ab) responses in sera and lachrymal secretions of vaccinated chickens. The results indicated that inactivated AIV and CpG ODN co-encapsulated in PLGA NPs (2x NanoAI+CpG) produced higher amounts of hemagglutination inhibiting antibodies compared to a group vaccinated with non-adjuvanted AIV encapsulated in PLGA NPs (NanoAI). The tested adjuvanted NPs-based vaccine (2x NanoAI+CpG) resulted in higher IgG responses in the sera and lachrymal secretions at weeks 3, 4 and 5 post-vaccination when immunized subcutaneously. The incorporation of CpG ODN led to an increase in Ab-mediated responses and was found useful to be included both in the prime and booster vaccinations. In the second study, the ability of chitosan and mannan coated PLGA NPs that encapsulated AIV and CpG ODN was evaluated for inducing antibody responses when delivered via nasal and ocular routes in one-week-old SPF layer-type chickens. These PLGA NPs-based and surface modified formulations induced robust AIV-specific antibody responses in sera and lachrymal secretions. Chitosan coated PLGA NPs resulted in the production of large quantities of lachrymal IgA and IgG compared to mannan coated NPs, which also induced detectable amounts of IgA in addition to the induction of IgG in lachrymal secretions. In both mucosal and subcutaneous vaccination approaches, although NPs delivery enhanced Ab-mediated immunity, one booster vaccination was required to generate significant amount of Abs. These results highlight the potential of NPs-based AIV antigens for promoting the induction of both systemic and mucosal immune responses against respiratory pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Administration, Ophthalmic
  • Animals
  • Antigens, Viral / immunology
  • Chickens* / immunology
  • Chickens* / virology
  • Drug Compounding / methods
  • Female
  • Immunity, Mucosal* / drug effects
  • Immunization
  • Immunization, Secondary / methods
  • Immunization, Secondary / veterinary
  • Immunogenicity, Vaccine / physiology*
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology
  • Influenza in Birds / immunology
  • Influenza in Birds / therapy*
  • Injections, Subcutaneous
  • Mucous Membrane / drug effects
  • Mucous Membrane / immunology
  • Mucous Membrane / metabolism
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Oligodeoxyribonucleotides / administration & dosage
  • Oligodeoxyribonucleotides / chemistry
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / chemistry
  • Poultry Diseases / immunology
  • Poultry Diseases / therapy*
  • Poultry Diseases / virology
  • Vaccination* / methods
  • Vaccination* / veterinary
  • Vaccines, Inactivated

Substances

  • Antigens, Viral
  • CPG-oligonucleotide
  • Influenza Vaccines
  • Oligodeoxyribonucleotides
  • Vaccines, Inactivated
  • Polyglycolic Acid

Grants and funding

This work was supported by the Ontario Ministry of Agriculture, Food and Rural Affairs (OMAFRA), the Canadian Poultry Research Council (CPRC) and Agriculture and Agri-Food Canada. This research is supported in part by the University of Guelph’s Food from Thought initiative, thanks to funding from the Canada First Research Excellence Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.