Your browser doesn't support javascript.
Antibodies to Crucial Epitopes on HSV-2 Glycoprotein D as a Guide to Dosing an mRNA Genital Herpes Vaccine.
Hook, Lauren M; Awasthi, Sita; Cairns, Tina M; Alameh, Mohamad-Gabriel; Fowler, Bernard T; Egan, Kevin P; Sung, Molly M H; Weissman, Drew; Cohen, Gary H; Friedman, Harvey M.
  • Hook LM; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Awasthi S; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Cairns TM; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Alameh MG; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Fowler BT; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Egan KP; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Sung MMH; Acuitas Therapeutics Inc., Vancouver, BC V6T 1Z3, Canada.
  • Weissman D; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Cohen GH; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Friedman HM; Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Viruses ; 14(3)2022 03 05.
Article in English | MEDLINE | ID: covidwho-1765948
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Herpes Genitalis Type of study: Experimental Studies Topics: Vaccines Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: V14030540

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccines / Herpes Genitalis Type of study: Experimental Studies Topics: Vaccines Limits: Animals Language: English Year: 2022 Document Type: Article Affiliation country: V14030540