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Vaccine. 2013 Nov 12;31(47):5594-601. doi: 10.1016/j.vaccine.2013.06.068. Epub 2013 Jul 2.

Absence of systemic toxicity changes following intramuscular administration of novel pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines to BALB/c mice.

Author information

1
The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

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.

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

PMID:
23831324
PMCID:
PMC3898262
DOI:
10.1016/j.vaccine.2013.06.068
[Indexed for MEDLINE]
Free PMC Article

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