title: Toxicology, biodistribution and shedding profile of a recombinant measles vaccine vector expressing HIV-1 antigens, in cynomolgus macaques.
abstract: As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live-attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered to express the F4 antigen (MV1-F4). F4 is a fusion protein comprising HIV-1 antigens p17 and p24, reverse transcriptase and Nef. This study assessed the toxicity, biodistribution and shedding profiles of MV1-F4. Cynomolgus macaques were intramuscularly immunized one or three times with the highest dose of MV1-F4 intended for clinical use, the reference (Schwarz) measles vaccine or saline, and monitored clinically for 11 or 85 days. Toxicological parameters included local and systemic clinical signs, organ weights, haematology, clinical and gross pathology and histopathology. Both vaccines were well tolerated, with no morbidity, clinical signs or gross pathological findings observed. Mean spleen weights were increased after three doses of either vaccine, which corresponded with increased numbers and/or sizes of germinal centers. This was likely a result of the immune response to the vaccines. Either vaccine virus replicated preferentially in secondary lymphoid organs and to a lesser extent in epithelium-rich tissues (e.g., intestine, urinary bladder and trachea) and the liver. At the expected peak of viremia, viral RNA was detected in some biological fluid samples from few animals immunized with either vaccine, but none of these samples contained infectious virus. In conclusion, no shedding of infectious viral particles was identified in cynomolgus monkeys after injection of MV1-F4 or Schwarz measles vaccines. Furthermore, no toxic effect in relation to the MV vaccination was found with these vaccines in this study.
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Lorin
authors.forename: Lawrence
authors.initials: L
authors.lastname: Segal
authors.forename: Johann
authors.initials: J
authors.lastname: Mols
authors.forename: Danielle
authors.initials: D
authors.lastname: Morelle
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourguignon
authors.forename: Olga
authors.initials: O
authors.lastname: Rovira
authors.forename: Pascal
authors.initials: P
authors.lastname: Mettens
authors.forename: Jérémy
authors.initials: J
authors.lastname: Silvano
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dumey
authors.forename: Frédérick
authors.initials: F
authors.lastname: Le Goff
authors.forename: Marguerite
authors.initials: M
authors.lastname: Koutsoukos
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D005260:Female; D005818:Genetic Engineering / Q000379:methods; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007273:Injections, Intramuscular; D008252:Macaca fascicularis; D008297:Male; D008458:Measles Vaccine / Q000276:immunology* / Q000493:pharmacokinetics / Q000633:toxicity; D008459:Measles virus / Q000276:immunology*; D009929:Organ Size / Q000276:immunology; D012367:RNA, Viral / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens; D008458:Measles Vaccine; D012367:RNA, Viral