Nonclinical safety evaluation of two vaccine candidates for herpes simplex virus type 2 to support combined administration in humans. Issue 4 (22nd November 2022)

• Record Type: Journal Article
• Authors: Piras, Fabienne; Plitnick, Lisa M.; Berglund, Peter; Bernard, Marie‐Clotilde; Desert, Paul
• Is Part Of: Journal of applied toxicology. Volume 43:Issue 4(2023)
• Page Start: 534
• Page End: 556
• Publication Date: 2022-11-22
• Subjects: G103 vaccine -- genital herpes -- GLA‐SE adjuvant -- HSV‐2 -- HSV529 vaccine -- live attenuated virus vaccine -- nonclinical safety evaluation -- prime‐boosting -- vaccine; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.4404
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Herpes simplex virus type 2 (HSV‐2) is the most common cause of genital disease worldwide. The development of an effective HSV‐2 vaccine would significantly impact global health based on the psychological distress caused by genital herpes for some individuals, the risk transmitting the infection from mother to infant, and the elevated risk of acquiring HIV‐1. Five nonclinical safety studies were conducted with the replication defective HSV529 vaccine, alone or adjuvanted with GLA‐SE, and the G103 subunit vaccine containing GLA‐SE. A biodistribution study was conducted in guinea pigs to evaluate distribution, persistence, and shedding of HSV529. A preliminary immunogenicity study was conducted in rabbits to demonstrate HSV529‐specific humoral response and its enhancement by GLA‐SE. Three repeated‐dose toxicity studies, one in guinea pigs and two in rabbits, were conducted to assess systemic toxicity and local tolerance of HSV529, alone or adjuvanted with GLA‐SE, or G103 containing GLA‐SE. Data from these studies show that both vaccines are safe and well tolerated and support the ongoing HSV‐2 clinical trial in which the two vaccine candidates will be given either sequentially or concomitantly to explore their potential synergistic and incremental effects. Abstract : Herpes simplex virus type 2 (HSV‐2) is the most common cause of genital disease worldwide, with no preventive or curative vaccine available. Five nonclinical safety studies were conducted with the replication defective HSV529 vaccine, alone or adjuvanted with GLA‐SE, and the G103 subunit vaccine containing GLA‐SE. The two vaccine candidates were found safe and well tolerated supporting the ongoing HSV‐2 clinical trial in which they will be given either sequentially or concomitantly to explore their potential synergistic and incremental effects.