tetano
Editor, Senior Moderator
J Virol
. 2021 Jun 2;JVI0084121.
doi: 10.1128/JVI.00841-21. Online ahead of print.
Intranasal nanoparticle vaccination elicits a persistent, polyfunctional CD4 T cell response in the murine lung specific for a highly conserved influenza antigen that are sufficient to mediate protection from influenza virus challenge
Sean A Nelson[SUP] 1 [/SUP], Thamotharampillai Dileepan[SUP] 2 [/SUP], Amy Rasley[SUP] 3 [/SUP], Marc K Jenkins[SUP] 2 [/SUP], Nicholas O Fischer[SUP] 3 [/SUP], Andrea J Sant[SUP] 1 [/SUP]
Affiliations
Abstract
Lung-localized CD4 T cells play a critical role in the control of influenza virus infection and can provide broadly protective immunity. However, current influenza vaccination strategies primarily target influenza hemagglutinin (HA) and are administered peripherally to induce neutralizing antibodies. We have used an intranasal vaccination strategy targeting the highly conserved influenza nucleoprotein (NP) to elicit broadly protective lung localized CD4 T cell responses. The vaccine platform consists of a self-assembling nanolipoprotein particle (NLP) linked to NP with an adjuvant. We have evaluated the functionality, in vivo localization and persistence of T cells elicited. Our study revealed that intranasal vaccination elicits a polyfunctional subset of lung-localized CD4 T cells that persist long term. A subset of these lung CD4 T cells localize to the airway, where they can act as early responders following encounter with cognate antigen. Polyfunctional CD4 cells isolated from airway and lung tissue produce significantly more effector cytokines IFNγ and TNFα as well as cytotoxic functionality. When adoptively transferred to naïve recipients, CD4 T cells from NLP:NP immunized lung were sufficient to mediate 100% survival from lethal challenge with H1N1 influenza virus. Importance Exploiting new, more efficacious strategies to potentiate influenza-specific immune responses is important, particularly for at-risk populations. We have demonstrated the promise of direct intranasal protein vaccination to establish long-lived immunity in the lung with CD4 T cells that possess features and positioning in the lung that are associated with both immediate and long-term immunity, as well as demonstrating direct protective potential.
. 2021 Jun 2;JVI0084121.
doi: 10.1128/JVI.00841-21. Online ahead of print.
Intranasal nanoparticle vaccination elicits a persistent, polyfunctional CD4 T cell response in the murine lung specific for a highly conserved influenza antigen that are sufficient to mediate protection from influenza virus challenge
Sean A Nelson[SUP] 1 [/SUP], Thamotharampillai Dileepan[SUP] 2 [/SUP], Amy Rasley[SUP] 3 [/SUP], Marc K Jenkins[SUP] 2 [/SUP], Nicholas O Fischer[SUP] 3 [/SUP], Andrea J Sant[SUP] 1 [/SUP]
Affiliations
- PMID: 34076479
- DOI: 10.1128/JVI.00841-21
Abstract
Lung-localized CD4 T cells play a critical role in the control of influenza virus infection and can provide broadly protective immunity. However, current influenza vaccination strategies primarily target influenza hemagglutinin (HA) and are administered peripherally to induce neutralizing antibodies. We have used an intranasal vaccination strategy targeting the highly conserved influenza nucleoprotein (NP) to elicit broadly protective lung localized CD4 T cell responses. The vaccine platform consists of a self-assembling nanolipoprotein particle (NLP) linked to NP with an adjuvant. We have evaluated the functionality, in vivo localization and persistence of T cells elicited. Our study revealed that intranasal vaccination elicits a polyfunctional subset of lung-localized CD4 T cells that persist long term. A subset of these lung CD4 T cells localize to the airway, where they can act as early responders following encounter with cognate antigen. Polyfunctional CD4 cells isolated from airway and lung tissue produce significantly more effector cytokines IFNγ and TNFα as well as cytotoxic functionality. When adoptively transferred to naïve recipients, CD4 T cells from NLP:NP immunized lung were sufficient to mediate 100% survival from lethal challenge with H1N1 influenza virus. Importance Exploiting new, more efficacious strategies to potentiate influenza-specific immune responses is important, particularly for at-risk populations. We have demonstrated the promise of direct intranasal protein vaccination to establish long-lived immunity in the lung with CD4 T cells that possess features and positioning in the lung that are associated with both immediate and long-term immunity, as well as demonstrating direct protective potential.