Lack of developmental neurotoxicity of MN rgp 120/HIV-1 administered subcutaneously to neonatal rats

• Published in: Toxicological sciences Vol. 48; no. 1; pp. 90 - 99
• Main Authors: Bussiere, J L, Hardy, L M, Peterson, M, Foss, J A, Garman, R H, Hoberman, A M, Christian, M S
• Format: Journal Article
• Language: English
• Published: United States 01.03.1999
• Subjects: AIDS Vaccines - toxicity; Animals; Animals, Newborn; Avoidance Learning - drug effects; Behavior, Animal - drug effects; Body Weight - drug effects; Brain - drug effects; Brain - embryology; Brain - physiopathology; Embryonic and Fetal Development - drug effects; Female; HIV Envelope Protein gp120 - immunology; Injections, Subcutaneous; Maze Learning - drug effects; Milk - immunology; Motor Activity - drug effects; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Sexual Maturation - drug effects; Vaccines, Synthetic - toxicity
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/48.1.90

The potential for neurotoxic effects was evaluated in rat off-spring after exposure in utero and/or during the neonatal period to a recombinant subunit vaccine of gp120 prepared from the MN strain of HIV-1 (MN rgp 120/HIV-1). Thirty pregnant female rats were given MN rgp120/HIV-1 with alum adjuvant, and 30 rats were given vehicle, once every 3 days from Day 1 of presumed gestation until parturition. One pup/sex/litter from treated and control group dams were given a daily subcutaneous injection, from Day 1 through Day 22 postpartum (PP) of vehicle, MN rgp120/HIV-1, MN rgp120/HIV-1 with alum, or MN rgp120/HIV-1 with QS-21 adjuvant. Neurobehavioral and physical development were evaluated (preweaning reflex and development, sexual maturation, motor activity, acoustic startle, passive avoidance, functional observational battery, and water M-maze testing), and tissues were processed for anatomical examination (whole and regional brain weights, and neuropathology). Administration of MN rgp120/HIV-1, with or without adjuvant, to pups did not cause any persistent effect on any parameter evaluated. Neurohistological examination did not reveal any pathological effects related to treatment. Thus, MN rgp120/HIV-1 alone or formulated as a vaccine does not cause neurotoxicity or developmental toxicity in neonatal rats after exposure in utero and/or during the neonatal period.