Enhancement of antigen-specific CD4+ and CD8+ T cell responses using a self-assembled biologic nanolipoprotein particle vaccine. Issue 11 (13th March 2017)

• Record Type: Journal Article
• Authors: Weilhammer, Dina; Dunkle, Alexis D.; Blanchette, Craig D.; Fischer, Nicholas O.; Corzett, Michele; Lehmann, Doerte; Boone, Tyler; Hoeprich, Paul; Driks, Adam; Rasley, Amy
• Is Part Of: Vaccine. Volume 35:Issue 11(2017)
• Page Start: 1475
• Page End: 1481
• Publication Date: 2017-03-13
• Subjects: Nanolipoprotein -- Nanoparticle -- Intranasal -- Vaccine -- T cell activation -- Nanodisc; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2017.02.004
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: The model antigen OVA was covalently conjugated to nanolipoprotein particles (NLPs). NLP conjugation enhanced uptake of OVA by antigen presenting cells in vitro . NLP conjugation enhanced CD4 + and CD8 + T cell responses to OVA in vitro and in vivo . Abstract: To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4 + and CD8 + T cells in vitro compared to co-administration of free OVA and MPLA. Upon intranasal immunization of mice harboring TCR-transgenic cells, NLPs enhanced the adjuvant effects of MPLA and the in vivo delivery of OVA, leading to significantly increased expansion of CD4 + and CD8 + T cells in lung-draining lymph nodes. Therefore, NLPs are a promising vaccine platform for inducing T cell responses following intranasal administration.