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iScience . Mucosal boosting increases protective efficacy of an influenza vaccine in mice

tetano

Editor, Senior Moderator
iScience


. 2025 May 21;28(6):112721.
doi: 10.1016/j.isci.2025.112721. eCollection 2025 Jun 20. Mucosal boosting increases protective efficacy of an influenza vaccine in mice

Liping Wang[SUP] 1 [/SUP], Chi Ngai Chan[SUP] 1 [/SUP], Jayeshbhai Chaudhari[SUP] 1 [/SUP], David Hope[SUP] 1 [/SUP], Alejandro A Espinosa Perez[SUP] 1 [/SUP], Ninaad Lasrado[SUP] 1 [/SUP], Zhenyu Li[SUP] 1 [/SUP], Alejandra Waller-Pulido[SUP] 1 [/SUP], Dalia N Cabrera-Barragan[SUP] 1 [/SUP], Brookelynne Verette[SUP] 1 [/SUP], Samuel J Nangle[SUP] 1 [/SUP], Jose Ayala-Bernot[SUP] 1 [/SUP], Catherine Jacob-Dolan[SUP] 1 2 3 [/SUP], Michelle Lifton[SUP] 1 [/SUP], Ellis Strutton[SUP] 1 [/SUP], Jana Fisher[SUP] 1 [/SUP], Esther Mbiwan[SUP] 1 [/SUP], Annika Rossler[SUP] 1 [/SUP], Sara Schrag[SUP] 1 [/SUP], Dan H Barouch[SUP] 1 2 3 [/SUP]



Affiliations
Abstract

Influenza virus infection is a significant cause of global mortality. However, the development of influenza vaccines that induce robust immune responses at the site of respiratory mucosal exposure has proven challenging. Here, we assessed immune responses and protective efficacy of a rhesus adenovirus serotype 52 (RhAd52) vectored influenza vaccine encoding the hemagglutinin (HA) glycoprotein from A/California/07/2009 administrated by systemic or mucosal routes of immunization. We observed robust and durable systemic and mucosal immunity, including IgA and tissue resident memory T cells in the respiratory mucosa, in mice that received the vaccine intranasally or intratracheally. In contrast, only systemic immune responses were observed in mice that received the vaccine intramuscularly. Moreover, a single intranasal or intratracheal dose of RhAd52-HA provided near complete protection against a lethal challenge with a mouse-adapted influenza virus strain, whereas intramuscular immunization with RhAd52-HA and mRNA-HA provided less robust protection. Our data demonstrate the importance of mucosal immunity for enhancing vaccine protection against influenza.

Keywords: Immunity; Virology.




 
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