Journal Article

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

Belsuzarri, Masiel M., Sako, Yukiya, Shukla, Nikunj M., Chan, Michael, Jin, Jasmine, Carson, Dennis A., Sato-Kaneko, Fumi, Lao, Fitzgerald S., Cottam, Howard B., Hayashi, Tomoko, Yao, Shiyin

2022

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Antigens / combination adjuvant / COVID-19 / Dosage and administration / Ethylenediaminetetraacetic acid / FDA approval / Health aspects / IgG antibody / Immune response / Immunity / Immunoglobulin A / Immunoglobulin G / Immunological adjuvants / Immunological memory / Infections / Influenza / Influenza A / Influenza vaccines / influenza virus infection / Influenza viruses / Intranasal medication / intranasal pulmonary boosting regimen / Laboratories / Lavage / liposomal formulation / Lymphocytes / Lymphocytes T / Memory cells / Mucosal immunity / Pandemics / Pharmaceutical research / Priming / Public health / Respiratory tract / Scientific equipment and supplies industry / T cells / TLR4 agonist / TLR4 protein / TLR7 agonist / Toll-like receptors / Vaccination / Vaccines / Viral proteins / Viruses