Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine

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School of Dental Medicine::Departmental Papers (Dental)
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Dentistry
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herpes simplex virus type 2; nucleoside-modified mRNA; lipid nanoparticle; glycoprotein D; genital herpes vaccine; IgG ELISA; neutralizing antibodies; epitope mapping; surface plasmon resonance
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2022
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Lauren M. Hook; Sita Awasthi; Tina M. Cairns; Mohamad-Gabriel Alameh; Bernard T. Fowler; Kevin P. Egan; Molly M. H. Sung; Drew Weissman; Gary H. Cohen; Harvey M. Friedman
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Abstract

The toxicity of mRNA-lipid nanoparticle (LNP) vaccines depends on the total mRNA-LNP dose. We established that the maximum tolerated dose of our trivalent mRNA-LNP genital herpes vaccine was 10 μg/immunization in mice. We then evaluated one of the mRNAs, gD2 mRNA-LNP, to determine how much of the 10 μg total dose to assign to this immunogen. We immunized mice with 0.3, 1.0, 3.0, or 10 μg of gD2 mRNA-LNP and measured serum IgG ELISA, neutralizing antibodies, and antibodies to six crucial gD2 epitopes involved in virus entry and spread. Antibodies to crucial gD2 epitopes peaked at 1 μg, while ELISA and neutralizing titers continued to increase at higher doses. The epitope results suggested no immunologic benefit above 1 μg of gD2 mRNA-LNP, while ELISA and neutralizing titers indicated higher doses may be useful. We challenged the gD2 mRNA-immunized mice intravaginally with HSV-2. The 1-μg dose provided total protection, confirming the epitope studies, and supported assigning less than one-third of the trivalent vaccine maximum dose of 10 μg to gD2 mRNA-LNP. Epitope mapping as performed in mice can also be accomplished in phase 1 human trials to help select the optimum dose of each immunogen in a multivalent vaccine.

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14
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2022-03-05
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MDPI
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