Browsing by Subject "Herpes Simplex"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    A non-neutralizing glycoprotein B monoclonal antibody protects against herpes simplex virus disease in mice.
    (The Journal of clinical investigation, 2023-02) Kuraoka, Masayuki; Aschner, Clare Burn; Windsor, Ian W; Mahant, Aakash Mahant; Garforth, Scott J; Kong, Susan Luozheng; Achkar, Jacqueline M; Almo, Steven C; Kelsoe, Garnett; Herold, Betsy C
    There is an unmet need for monoclonal antibodies (mAbs) for prevention or as adjunctive treatment of herpes simplex virus (HSV) disease. Most vaccine and mAb efforts focus on neutralizing antibodies, but for HSV this strategy has proven ineffective. Preclinical studies with a candidate HSV vaccine strain, ΔgD-2, demonstrated that non-neutralizing antibodies that activate Fcγ receptors (FcγRs) to mediate antibody-dependent cellular cytotoxicity (ADCC) provide active and passive protection against HSV-1 and HSV-2. We hypothesized that this vaccine provides a tool to identify and characterize protective mAbs. We isolated HSV-specific mAbs from germinal center and memory B cells and bone marrow plasmacytes of ΔgD-2-vaccinated mice and evaluated these mAbs for binding, neutralizing, and FcγR-activating activity and for protective efficacy in mice. The most potent protective mAb, BMPC-23, was not neutralizing but activated murine FcγRIV, a biomarker of ADCC. The cryo-electron microscopic structure of the Fab-glycoprotein B (gB) assembly identified domain IV of gB as the epitope. A single dose of BMPC-23 administered 24 hours before or after viral challenge provided significant protection when configured as mouse IgG2c and protected mice expressing human FcγRIII when engineered as a human IgG1. These results highlight the importance of FcR-activating antibodies in protecting against HSV.
  • Thumbnail Image
    ItemOpen Access
    Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease.
    (Early human development, 2022-07) Ericson, Jessica E; Benjamin, Daniel K; Boakye-Agyeman, Felix; Balevic, Stephen J; Cotten, C Michael; Adler-Shohet, Felice; Laughon, Matthew; Poindexter, Brenda; Harper, Barrie; Payne, Elizabeth H; Kaneshige, Kim; Smith, P Brian; Best Pharmaceuticals for Children Act - Pediatric Trials Network

    Background

    Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.

    Aims

    Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).

    Study design

    We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model.

    Subjects

    Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals.

    Outcome measures

    We identified clinical and laboratory adverse events (AEs).

    Results and conclusions

    We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2-37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.