mRNA-LNP vaccines encoding for optimized prM-ENV proteins of Dengue virus serotypes 1-4 induce robust and protective immunity without ADE

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B551
Abstract ID: 6117

Presenting Author:
Enzo LaMontia-Hankin , Graduate Student at Univ. of Illinois Col. of Med.

Abstract:

Dengue virus (DENV) consists of four distinct serotypes, DENV 1-4, and it is the most common mosquito-borne virus in the world, causing nearly 400 million infections annually. Despite DENV’s prevalence in tropical areas of the world, current vaccines are not approved for all populations. While primary DENV infections typically cause mild febrile illness, heterotypic secondary infections can cause Dengue hemorrhagic fever and death due in-part to antibody-dependent-enhancement (ADE). We have engineered nucleotide modified mRNA-LNP DENV vaccines for each serotype that encodes the premembrane (prM) and envelope (E) proteins. Upon translation, the mRNA vaccines form viral like particles (VLP’s) that maintain the same antigenic landscape found on DENV. The E protein has been modified to increase VLP stability and antigen expression and to remove epitopes known to drive ADE. Our synthesized mRNA-LNP vaccines elicited neutralizing titers of serotype specific antibodies in mice and are protective against a lethal homotypic DENV challenge.  Importantly our vaccines did not induce ADE antibodies characteristic of the canonical polyclonal response to a DENV infection. Cumulatively, we have now generated DENV mRNA-LNP vaccines against all DENV serotypes and these vaccines generate protective immunity without ADE in mouse models.