Intranasal Nanoparticle Vaccination Elicits a Persistent, Polyfunctional CD4 T Cell Response in the Murine Lung Specific for a Highly Conserved Influenza Virus Antigen That Is Sufficient To Mediate Protection from Influenza Virus Challenge

Nelson, Sean A.; Dileepan, Thamotharampillai; Rasley, Amy; Jenkins, Marc K.; Fischer, Nicholas O.; Sant, Andrea J.

doi:10.1128/jvi.00841-21

Title: Intranasal Nanoparticle Vaccination Elicits a Persistent, Polyfunctional CD4 T Cell Response in the Murine Lung Specific for a Highly Conserved Influenza Virus Antigen That Is Sufficient To Mediate Protection from Influenza Virus Challenge

Journal Article · Mon Jul 26 00:00:00 EDT 2021 · Journal of Virology

DOI:https://doi.org/10.1128/jvi.00841-21· OSTI ID:1889526

Nelson, Sean A. ^[1]; Dileepan, Thamotharampillai ^[2]; Rasley, Amy ^[3]; Jenkins, Marc K. ^[2]; Fischer, Nicholas O. ^[3];

^[1]

University of Rochester Medical Center, NY (United States)
University of Minnesota Medical School, Minneapolis, MN (United States)
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

We report 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 the 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 T cells isolated from airway and lung tissue produce significantly more effector cytokines IFN-γ and TNF-α, as well as cytotoxic functionality. When adoptively transferred to naive recipients, CD4 T cells from NLP:NP-immunized lung were sufficient to mediate 100% survival from lethal challenge with H1N1 influenza virus.

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Research Organization:: Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE National Nuclear Security Administration (NNSA); NIAID Centers of Excellence; National Institutes of Health (NIH)

Grant/Contract Number:: AC52-07NA27344; HHSN272201400005C; HHSN272201400005C-17A; 5T32HL066988-19

OSTI ID:: 1889526

Report Number(s):: LLNL-JRNL-839502; 1060144

Journal Information:: Journal of Virology, Vol. 95, Issue 16; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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Title: Intranasal Nanoparticle Vaccination Elicits a Persistent, Polyfunctional CD4 T Cell Response in the Murine Lung Specific for a Highly Conserved Influenza Virus Antigen That Is Sufficient To Mediate Protection from Influenza Virus Challenge

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