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Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice
- Source :
- Vaccines, Volume 8, Issue 3, Vaccines, Vol 8, Iss 519, p 519 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Along with their excellent safety profiles, subunit vaccines are typically characterized by much weaker immunogenicity and protection efficacy compared to whole-pathogen vaccines. Here, we present an approach aimed at bridging this disadvantage that is based on synergistic collaboration between pattern-recognition receptors (PRRs) belonging to different families. We prepared a model subunit vaccine formulation using an influenza hemagglutinin antigen incorporated into poly-(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with monophosphoryl lipid A (TLR4 agonist) and muramyl dipeptide (NOD2 agonist). The efficacy studies were conducted in comparison to control vaccine formulations containing individual PRR agonists. We show that the complex adjuvant based on TLR4 and NOD2 agonists potentiates proinflammatory cell responses (measured by activity of transcription factors and cytokine production both in vitro and in vivo) and enhances the phagocytosis of vaccine particles up to comparable levels of influenza virus uptake. Finally, mice immunized with vaccine nanoparticles containing both PRR agonists exhibited enhanced humoral (IgG, hemagglutination-inhibition antibody titers) and cellular (percentage of proliferating CD4+ T-cells, production of IFNɣ) immunity, leading to increased resistance to lethal influenza challenge. These results support the idea that complex adjuvants stimulating different PRRs may present a better alternative to individual PAMP-based adjuvants and could further narrow the gap between the efficacy of subunit versus whole-pathogen vaccines.
- Subjects :
- 0301 basic medicine
Agonist
PAMPs
subunit vaccines
medicine.drug_class
medicine.medical_treatment
Immunology
lcsh:Medicine
Monophosphoryl Lipid A
synergy
complex adjuvant
Virus
Article
NOD2
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Antigen
Immunity
pattern-recognition receptors
Drug Discovery
medicine
Pharmacology (medical)
TLR4
Pharmacology
Chemistry
Immunogenicity
lcsh:R
PLGA
Virology
030104 developmental biology
Infectious Diseases
030220 oncology & carcinogenesis
nanoparticles
influenza
Adjuvant
Muramyl dipeptide
Subjects
Details
- Language :
- English
- ISSN :
- 2076393X
- Database :
- OpenAIRE
- Journal :
- Vaccines
- Accession number :
- edsair.doi.dedup.....03be338e8cd93bfaab4c771cd5c510d2
- Full Text :
- https://doi.org/10.3390/vaccines8030519