Biodistribution and toxicology evaluation of a recombinant measles Schwarz-based Lassa vaccine in cynomolgus macaques.

Abstract

MV-LASV is an investigational measles Schwarz-based vaccine for the prevention of Lassa fever. A repeated-dose toxicity study in cynomolgus macaques was performed to assess the biodistribution and local and systemic toxicological effects. Monkeys received three immunizations of MV-LASV or saline intramuscularly with a 2-week interval. An increase in anti-measles antibodies confirmed the reaction of the immune system to the vaccine backbone. Clinical observations, body weight, body temperature, local tolerance, electrocardiogram parameters, various clinical pathology parameters (hematology, coagulation urinalysis, serum chemistry, and C-reactive protein) were monitored. Gross pathology and histopathology of various tissues were evaluated. MV-LASV induced a mild increase in fibrinogen and C-reactive protein concentrations. This coincided with microscopic inflammation at the injection sites which partially or fully resolved following a 3-week recovery period. Viral RNA was found in secondary lymphoid organs and injection sites and gall bladder. No viral shedding to the environment was observed. Overall, the vaccine was locally and systemically well tolerated, supporting a first-in-human study.