Preclinical pharmacokinetics and biodistribution of human papillomavirus DNA vaccine delivered in human endogenous retrovirus envelope-coated baculovirus vector

Pharm Res. 2012 Feb;29(2):585-93. doi: 10.1007/s11095-011-0598-z. Epub 2011 Sep 23.

Abstract

Purpose: Test pharmacokinetics and biodistribution of a human papillomavirus(HPV)16L1 DNA vaccine delivered in human endogenous retrovirus envelope protein (HERV)-expressing baculovirus (AcHERV) and those of naked plasmid vaccine.

Method: HPV16L1 gene was administrated as a naked plasmid or in AcHERV to mice via intravenous and intramuscular routes. HPV16L1 gene was extracted and assayed by quantitative real-time polymerase chain reaction, which was determined to have a detection limit of 50 copies/µg genomic DNA..

Results: Mean residence times of HPV16L1 in AcHERV were 4.8- and 272.2-fold higher than naked HPV16L1 DNA vaccines after intramuscular and intravenous administration, respectively. Naked HPV16L1 DNA levels 1 month after injection were >3 orders of magnitude lower in each tissue tested than AcHERV-delivered HPV16L1, which was retained in most tissues without specific tissue tropism. AcHERV-delivered HPV16L1 administered intramuscularly persisted at the injection sites. However, the levels of copy numbers in muscle were low (1,800/μg genomic DNA) after 1 month, and undetectable after 6 months.

Conclusions: HPV16L1 delivered via AcHERV resides longer in the body than HPV16L1 in naked form. The lack of tissue tropism ensures the safety of AcHERV vectors for further development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / pharmacokinetics*
  • Vaccines, DNA / administration & dosage*
  • Vaccines, DNA / pharmacokinetics*

Substances

  • Papillomavirus Vaccines
  • Vaccines, DNA