Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis

Abstract

BackgroundmRNAs are highly versatile, non-toxic molecules that are easy to produce and store, which can allow transient protein expression in all cell types. The safety aspects of mRNA-based treatments in gene therapy make this molecule one of the most promising active components of therapeutic or prophylactic methods. The use of mRNA as strategy for the stimulation of the immune system has been used mainly in current strategies for the cancer treatment but until now no one tested this molecule as vaccine for infectious disease.ResultsWe produce messenger RNA of Hsp65 protein from Mycobacterium leprae and show that vaccination of mice with a single dose of 10 μg of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of Mycobacterium tuberculosis. Moreover it was shown that this immunization was associated with specific production of IL-10 and TNF-alpha in spleen. In order to determine if antigen presenting cells (APCs) present in the lung are capable of capture the mRNA, labeled mRNA-Hsp65 was administered by intranasal route and lung APCs were analyzed by flow cytometry. These experiments showed that after 30 minutes until 8 hours the populations of CD11c+, CD11b+ and CD19+ cells were able to capture the mRNA. We also demonstrated in vitro that mRNA-Hsp65 leads nitric oxide (NO) production through Toll-like receptor 7 (TLR7).ConclusionsTaken together, our results showed a novel and efficient strategy to control experimental tuberculosis, besides opening novel perspectives for the use of mRNA in vaccines against infectious diseases and clarifying the mechanisms involved in the disease protection we noticed as well.

Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity

“…The reason for this could be that the robust innate immune response mediated by cholera toxin facilitated the induction of an adaptive immune response following naked mRNA immunization in the nasal cavity. This corroborates data from another study demonstrating that nasally administered naked mRNA induces immune responses for the treatment of tuberculosis26.…”

TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice

“…In a separate study, Kasturi and colleagues showed that purified HA alone did not elicit virusneutralizing antibody titers, whereas the addition of a TLR7 ligand to HA increased antibody production in mice (30). The additions of synthetic TLR7 agonist to subunit-, purified protein-, or mRNA-based vaccines were shown to enhance the immunogenicity of vaccines against a variety of targets (17,29,39,53,62). Collectively, these studies show that the presence of vRNA that engages TLR7 signaling contributes to the immunogenicity of commercially available TIVs.…”

DNA Vaccines for the Induction of Immune Responses in Mucosal Tissues

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