title: Absence of systemic toxicity changes following intramuscular administration of novel pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines to BALB/c mice.
abstract: BACKGROUND
  The systemic toxicity of three candidate HIV-1 vaccines plasmid pSG2.HIVconsv DNA (D), ChAdV63.HIVconsv (C) and MVA.HIVconsv (M) expressing chimeric immunogen derived from the most conserved regions of the HIV-1 proteome was evaluated in two repeat-dose studies in the male and female BALB/c mice.
  
  
  METHODS
  In study UNO011, mice received three doses of 2×10(7) plaque-forming units of MVA.HIVconsv vaccine (MMM). In study UNO012, mice received 3 doses of 50μg of pSG2.HIVconsv DNA followed by a single dose of 5.95×10(9) virus particles of ChAdV63.HIVconsv vaccine (DDDC). Similarly constituted control groups received the vehicle alone (phosphate buffered saline) at the same volume-dose. All vaccines were administered by intramuscular needle injection into the right hind limb at 14-day intervals and animals were sacrificed 7 days after the last dose. Assessment of local and systemic toxicity was made. Induction of HIV-1-specific responses was confirmed. Parameters assessed included clinical condition, body weight, food consumption, ophthalmoscopy, haematology, blood chemistry, organ weight and macroscopic and microscopic pathology.
  
  
  RESULTS
  In both studies, treatment with the candidate vaccines elicited strong HIV-1-specific T-cell responses. The vaccine treatment was well-tolerated without any adverse systemic toxicological changes. The local toxicity findings observed in these studies were consistent with the predicted response to a vaccine/substance administration by intramuscular injection.
  
  
  CONCLUSIONS
  The three novel anti-HIV-1 vaccines were well tolerated when administered by intramuscular injection to BALB/c mice. These results supported an application for authorisation by the Medicines and Healthcare Products Regulatory Agency of the UK to test these vaccines for the first time in phase I clinical trials in healthy both uninfected subjects and HIV-1-infected patients stable on antiretroviral treatment.
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ondondo
authors.forename: Caroline
authors.initials: C
authors.lastname: Brennan
authors.forename: Alfredo
authors.initials: A
authors.lastname: Nicosia
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Crome
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004337:Drug Carriers; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic
keywords: ALP; ALT; AST; Chimpanzee adenovirus; Conserved regions of HIV-1; HIV-1 vaccines; Hb; Hct; LUC; MCHC; MCV; MVA; Modified vaccinia virus Ankara (MVA); Plasmid DNA; Plt; Pre-clinical toxicity; RBC; WBC; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; erythrocyte; gGT; gamma-glutamyl transpeptidase; haematocrit; haemoglobin; large unstained cells; mean cell haemoglobin concentration; mean cell volume; modified vaccinia virus Ankara; platelet; total white cell count