Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Autor: Harshad P. Patil, Rita Vanbever, Nikolai Petrovsky, Gustavo Bracho, Wouter F. Tonnis, Jasmine Tomar, Henderik W. Frijlink, Wouter L. J. Hinrichs, Anke Huckriede
Přispěvatelé: UCL - SSS/LDRI - Louvain Drug Research Institute, Pharmaceutical Technology and Biopharmacy, Biopharmaceuticals, Discovery, Design and Delivery (BDDD), Translational Immunology Groningen (TRIGR), Nanotechnology and Biophysics in Medicine (NANOBIOMED)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
T-Lymphocytes
Pharmaceutical Science
Immune mechanisms
Antibodies
Viral
IMMUNOGENICITY
0302 clinical medicine
Influenza A Virus
H1N1 Subtype
Medicine
030212 general & internal medicine
B-Lymphocytes
Mice
Inbred BALB C
Mucosal
DELTA INULIN ADJUVANT
Protection
IMMUNE-RESPONSES
Immunogenicity
Inulin
Whole inactivated influenza vaccine
3. Good health
Vaccination
Inhalation
Influenza Vaccines
Female
Powders
Influenza vaccine
Respiratory Mucosa
Article
Advax
03 medical and health sciences
DELIVERY
Immune system
Adjuvants
Immunologic
Orthomyxoviridae Infections
Immunity
PULMONARY IMMUNIZATION
VACCINES
Administration
Inhalation
Animals
business.industry
Lethal dose
MEMORY
030104 developmental biology
Immunization
Vaccines
Inactivated
Immunology
ANTIBODIES
Nasal administration
POLYSACCHARIDE ADJUVANT
business
GENERATION
Zdroj: Journal of controlled release : official journal of the Controlled Release Society, Vol. 288, p. 199-211 (2018)
Journal of Controlled Release, 288, 199-211. Elsevier Bedrijfsinformatie b.v.
Journal of Controlled Release
ISSN: 0168-3659
Popis: Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1–5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.
Graphical abstract Unlabelled Image
Highlights • Effective Advax-adjuvanted powder influenza vaccine formulation can be prepared. • Advax enhances B and T cell immune responses to influenza vaccine. • Complete protection with Advax-adjuvanted influenza vaccine by pulmonary route. • Advax elicits robust B and T cell memory responses upon pulmonary administration. • Advax is a potent mucosal adjuvant.
Databáze: OpenAIRE
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