A Dual Adjuvant System for Intranasal Boosting of Local and Systemic Immunity for Influenza Vaccination

Autor: Fumi Sato-Kaneko, Shiyin Yao, Fitzgerald S. Lao, Yukiya Sako, Jasmine Jin, Nikunj M. Shukla, Howard B. Cottam, Michael Chan, Masiel M. Belsuzarri, Dennis A. Carson, Tomoko Hayashi
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Vaccines, Vol 10, Iss 10, p 1694 (2022)
Druh dokumentu: article
ISSN: 2076-393X
DOI: 10.3390/vaccines10101694
Popis: Systemically vaccinated individuals against COVID-19 and influenza may continue to support viral replication and shedding in the upper airways, contributing to the spread of infections. Thus, a vaccine regimen that enhances mucosal immunity in the respiratory mucosa is needed to prevent a pandemic. Intranasal/pulmonary (IN) vaccines can promote mucosal immunity by promoting IgA secretion at the infection site. Here, we demonstrate that an intramuscular (IM) priming-IN boosting regimen with an inactivated influenza A virus adjuvanted with the liposomal dual TLR4/7 adjuvant (Fos47) enhances systemic and local/mucosal immunity. The IN boosting with Fos47 (IN-Fos47) enhanced antigen-specific IgA secretion in the upper and lower respiratory tracts compared to the IM boosting with Fos47 (IM-Fos47). The secreted IgA induced by IN-Fos47 was also cross-reactive to multiple influenza virus strains. Antigen-specific tissue-resident memory T cells in the lung were increased after IN boosting with Fos47, indicating that IN-Fos47 established tissue-resident T cells. Furthermore, IN-Fos47 induced systemic cross-reactive IgG antibody titers comparable to those of IM-Fos47. Neither local nor systemic reactogenicity or adverse effects were observed after IN delivery of Fos47. Collectively, these results indicate that the IM/IN regimen with Fos47 is safe and provides both local and systemic anti-influenza immune responses.
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