Development of an Engineered Extracellular Vesicles-Based Vaccine Platform for Combined Delivery of mRNA and Protein To Induce Functional Immunity

Authors

Xin Luo
Kathleen M McAndrews
Kent A Arian
Sami J Morse
Viktoria Boeker
Shreyasee V Kumbhar
Yingying Hu
Krishnan K Mahadevan
Kaira A Church
Sriram Chitta
Nicolas T Ryujin
Janine Hensel
Jianli Dai
Dara P Dowlatshahi
Hikaru Sugimoto
Michelle L Kirtley
Valerie S LeBleu
Shabnam Shalapour
Joe H Simmons
Raghu Kalluri

Publication Date

10-1-2024

Journal

Journal of Control Release

Abstract

mRNA incorporated in lipid nanoparticles (LNPs) became a new class of vaccine modality for induction of immunity against COVID-19 and ushered in a new era in vaccine development. Here, we report a novel, easy-to-execute, and cost effective engineered extracellular vesicles (EVs)-based combined mRNA and protein vaccine platform (EVX-M+P vaccine) and explore its utility in proof-of-concept immunity studies in the settings of cancer and infectious disease. As a first example, we engineered EVs, natural nanoparticle carriers shed by all cells, to contain ovalbumin mRNA and protein (EVOvaM+P vaccine) to serve as cancer vaccine against ovalbumin-expressing melanoma tumors. EVOvaM+P administration to mice with established melanoma tumors resulted in tumor regression associated with effective humoral and adaptive immune responses. As a second example, we generated engineered EVs that contain Spike (S) mRNA and protein to serve as a combined mRNA and protein vaccine (EVSpikeM+P vaccine) against SARS-CoV-2 infection. EVSpikeM+P vaccine administration in mice and baboons elicited robust production of neutralizing IgG antibodies against RBD (receptor binding domain) of S protein and S protein specific T cell responses. Our proof-of-concept study describes a new platform with an ability for rapid development of combination mRNA and protein vaccines employing EVs for deployment against cancer and other diseases.

Keywords

Animals, Extracellular Vesicles, COVID-19 Vaccines, Cancer Vaccines, RNA, Messenger, COVID-19, Ovalbumin, Mice, Inbred C57BL, Mice, Female, Nanoparticles, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Humans, Cell Line, Tumor, Melanoma, Lipids, Liposomes

DOI

10.1016/j.jconrel.2024.08.017

PMID

39146981

PMCID

PMC11978227

PubMedCentral® Posted Date

4-8-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes