Quillaja brasiliensis nanoparticle adjuvant formulation improves the efficacy of an inactivated trivalent influenza vaccine in mice

Frontiers in Immunology

Immunology

Samuel P. Cibulski¹  Jose A. Chabalgoity²  Soledad Sienra²  Fernando Silveira²  Mariana Rivera-Patron²  María Moreno²  Jackeline Checa³  Nikita Deshpande⁴  Mariana Baz⁵ 

[1] Centro de Biotecnologia – CBiotec, Laboratório de Biotecnologia Celular e Molecular, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil;Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;Unidad de Biología Parasitaria, Facultad de Ciencias, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay;World Health Organization Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;World Health Organization Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia;Department of Microbiology, Infectious Disease and Immunology, Faculty of Medicine, Université Laval, Quebec City, QC, Canada;

关键词: Quillaja brasiliensis;    adjuvant;    ISCOM-matrices;    protection;    influenza virus;    intranasal route;    neutralizing antibodies;   

DOI  :  10.3389/fimmu.2023.1163858

 received in 2023-02-11, accepted in 2023-04-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

The threat of viral influenza infections has sparked research efforts to develop vaccines that can induce broadly protective immunity with safe adjuvants that trigger robust immune responses. Here, we demonstrate that subcutaneous or intranasal delivery of a seasonal trivalent influenza vaccine (TIV) adjuvanted with the Quillaja brasiliensis saponin-based nanoparticle (IMXQB) increases the potency of TIV. The adjuvanted vaccine (TIV-IMXQB) elicited high levels of IgG2a and IgG1 antibodies with virus-neutralizing capacity and improved serum hemagglutination inhibition titers. The cellular immune response induced by TIV-IMXQB suggests the presence of a mixed Th1/Th2 cytokine profile, antibody-secreting cells (ASCs) skewed toward an IgG2a phenotype, a positive delayed-type hypersensitivity (DTH) response, and effector CD4+ and CD8+ T cells. After challenge, viral titers in the lungs were significantly lower in animals receiving TIV-IMXQB than in those inoculated with TIV alone. Most notably, mice vaccinated intranasally with TIV-IMXQB and challenged with a lethal dose of influenza virus were fully protected against weight loss and lung virus replication, with no mortality, whereas, among animals vaccinated with TIV alone, the mortality rate was 75%. These findings demonstrate that TIV-IMXQB improved the immune responses to TIV, and, unlike the commercial vaccine, conferred full protection against influenza challenge.

【 授权许可】

Unknown   
Copyright © 2023 Silveira, Rivera-Patron, Deshpande, Sienra, Checa, Moreno, Chabalgoity, Cibulski and Baz