التفاصيل البيبلوغرافية
| العنوان: |
Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine |
| المؤلفون: |
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 |
| المصدر: |
Viruses, Vol 14, Iss 3, p 540 (2022) |
| بيانات النشر: |
MDPI AG, 2022. |
| سنة النشر: |
2022 |
| المجموعة: |
LCC:Microbiology |
| مصطلحات موضوعية: |
herpes simplex virus type 2, nucleoside-modified mRNA, lipid nanoparticle, glycoprotein D, genital herpes vaccine, IgG ELISA, Microbiology, QR1-502 |
| الوصف: |
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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1999-4915 |
| Relation: |
https://www.mdpi.com/1999-4915/14/3/540; https://doaj.org/toc/1999-4915 |
| DOI: |
10.3390/v14030540 |
| URL الوصول: |
https://doaj.org/article/76b703be13f248fdb48237fd38d0e99f |
| رقم الانضمام: |
edsdoj.76b703be13f248fdb48237fd38d0e99f |
| قاعدة البيانات: |
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