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Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine
- Source :
- Viruses; Volume 14; Issue 3; Pages: 540
- Publication Year :
- 2022
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2022.
-
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.
- Subjects :
- Vaccines
Herpes Genitalis
Herpesvirus 2, Human
Antibodies, Viral
Antibodies, Neutralizing
Epitopes
Mice
Infectious Diseases
Viral Envelope Proteins
Virology
Liposomes
Animals
Nanoparticles
RNA, Messenger
herpes simplex virus type 2
nucleoside-modified mRNA
lipid nanoparticle
glycoprotein D
genital herpes vaccine
IgG ELISA
neutralizing antibodies
epitope mapping
surface plasmon resonance
Subjects
Details
- Language :
- English
- ISSN :
- 19994915
- Database :
- OpenAIRE
- Journal :
- Viruses; Volume 14; Issue 3; Pages: 540
- Accession number :
- edsair.doi.dedup.....888d4dd4978073f3ecbad8659ff5b16e
- Full Text :
- https://doi.org/10.3390/v14030540