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

Abstract

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.

Intranasal COVID-19 vaccine induces respiratory memory T cells and protects K18-hACE mice against SARS-CoV-2 infection

“…administration of a synthetic DNA plasmid expressing Spike trimer with a chemokine adjuvant is effective at inducing mucosal antibodies and T cells 50 . A liposomal formulation containing TLR4 and TLR7 agonists was also shown to be an effective mucosal adjuvant for an influenza vaccine in mice 51 .…”

Potentials of saponins-based adjuvants for nasal vaccines

“…For example, a systemic prime-intranasal boost strategy with an influenza vaccine adjuvanted with the liposomal dual TLR4/7 adjuvant has been shown to enhance both systemic and local/mucosal immunity. This regimen results in the secretion of antigen-specific sIgA and development of tissue-resident memory T cells in the respiratory tracts, as well as cross-reactive sIgA to multiple influenza virus strains ( 140 ). Similarly, this prime-boost strategy has been successful in preventing SARS-CoV-2 transmission and disease development through vaccination ( 141 ).…”

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive AS01B-adjuvanted vaccine powders

“…The AS01 B was chosen in this study because a recent report from our group showed that AS01 B -containing vaccines can be converted to dry powders by TFF (AboulFotouh et al, 2022b). Results from a recent study have demonstrated the safety and efficacy of AS01 B as a potential nasal vaccine adjuvant in a mouse model (Sato-Kaneko et al, 2022). Moreover, one can find in the literature intranasal immunization studies wherein the vaccines contain either monophosphoryl lipid A (MPL) or QS21 as the adjuvant (Baldridge et al, 2000; Sasaki et al, 1998a; Sasaki et al, 1998b), and the liposomal AS01 B contains both MPL and QS21.…”