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Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.

ABSTRACT: The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8⁺ T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350-specific CD4⁺ T cells and EBV-specific CD8⁺ T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization. This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.

SUBMITTER: Dasari V

PROVIDER: S-EPMC10409721 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.

Dasari Vijayendra V McNeil Lisa K LK Beckett Kirrilee K Solomon Matthew M Ambalathingal George G Thuy T Le TL Panikkar Archana A Smith Caitlyn C Steinbuck Martin P MP Jakubowski Aniela A Seenappa Lochana M LM Palmer Erica E Zhang Jeff J Haqq Christopher M CM DeMuth Peter C PC Khanna Rajiv R

Nature communications 20230808 1

The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV. Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8<sup>+</sup> T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses ...[more]

PMID: 37553346

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Project description:PurposeTo determine the imaging and receptor-binding properties of a multireporter probe designed for sentinel lymph node (SLN) mapping via nuclear and fluorescence detection.Materials and methodsThe animal experiments were approved by the institutional animal care and use committee. A multireporter probe was synthesized by covalently attaching cyanine 7 (Cy7), a near-infrared cyanine dye, to tilmanocept, a radiopharmaceutical that binds to a receptor specific to recticuloendothelial cells. In vitro binding assays of technetium 99m (99mTc)-labeled Cy7 tilmanocept were conducted at 4°C by using receptor-bearing macrophages. Optical SLN imaging after foot pad administration was performed by using two molar doses of Cy7 tilmanocept. Six mice were injected with 0.11 nmol of 99mTc-labeled Cy7 tilmanocept (low-dose group); an additional six mice were injected with 31 nmol of 99mTc-labeled Cy7 tilmanocept (high-dose group) to saturate the receptor sites within the SLN. After 2.5 hours of imaging, the mice were euthanized, and the sentinel and distal lymph nodes were excised and assayed for radioactivity for calculation of SLN percentage of injected dose and extraction. Four mice were used as controls for autofluorescence. Standard optical imaging software was used to plot integrated fluorescence intensity against time for calculation of the SLN uptake rate constant and scaled peak intensity. Significance was calculated by using the Student t test.ResultsIn vitro binding assays showed subnanomolar affinity (mean dissociation constant, 0.25 nmol/L±0.10 [standard deviation]). Fluorescence imaging showed a detection sensitivity of 1.6×10(3) counts·sec(-1)·μW(-1) per picomole of Cy7. All four imaging metrics (percentage of injected dose, SLN extraction, SLN uptake rate constant, and expected peak fluorescence intensity) exhibited higher values (P=.005 to P=.042) in the low-dose group than in the high-dose group; this finding was consistent with receptor-mediated image formation.ConclusionThe multireporter probe 99mTc-labeled Cy7 tilmanocept exhibits in vitro and in vivo receptor-binding properties for successful receptor-targeted SLN mapping with nuclear and optical imaging.

Dataset Information

Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.

Publications

Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice.

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