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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

Authors :
A. I. Tukhvatulin
Alina S. Erokhova
Natalia V. Shevlyagina
Alina S. Dzharullaeva
Anastasia Zemskaya
Olga V. Zubkova
Alexander L. Gintsburg
Dmitry V. Shcheblyakov
Denis Y. Logunov
Vladimir G. Zhukhovitsky
T A Ozharovskaia
Irina Fedyakina
Maxim Balyasin
Ivan Pruss
Boris S. Naroditsky
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.

Details

Language :
English
ISSN :
2076393X
Database :
OpenAIRE
Journal :
Vaccines
Accession number :
edsair.doi.dedup.....03be338e8cd93bfaab4c771cd5c510d2
Full Text :
https://doi.org/10.3390/vaccines8030519