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Preclinical Pharmacokinetics and Biodistribution of Human Papillomavirus DNA Vaccine Delivered in Human Endogenous Retrovirus Envelope-Coated Baculovirus Vector

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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.

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Abbreviations

AcHERV:

human endogenous retrovirus envelope protein-expressing baculovirus

AUC:

area under the curve

AUMC:

area under the momentum curve

CV:

coefficient of variation

GAPDH:

glyceraldehyde 3-phosphate dehydrogenase

gDNA:

genomic DNA

HERV:

human endogenous retrovirus envelope protein

HPV:

human papillomavirus

MRT:

mean residence time

QRT-PCR:

quantitative real-time polymerase chain reaction

VLP:

virus-like particles

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ACKNOWLEDGMENTS & DISCLOSURES

This work has been financially supported by grants from the Korean Health Technology R&D Project (No. A092010), Ministry for Health, Welfare & Family Affairs, Republic of Korea, and from the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government (MEST) (No. 20110019640).

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Authors and Affiliations

  1. College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Daehak-dong, Gwanank-gu, Seoul, 151-742, South Korea

    Hee-Jeong Cho, Saewon Im, Mi-Gyeong Kim & Yu-Kyoung Oh

  2. Department of Molecular Medicine & Biopharmaceutical Sciences Graduate School of Convergence Science & Technology, Seoul National University, Seoul, South Korea

    Soondong Lee & Jaewoo Lee

  3. Department of Animal Biotechnology College of Animal Bioscience & Technology, Konkuk University, Seoul, 143-701, South Korea

    Hee-Jung Lee & Young Bong Kim

  4. Kolon Life Science, Seoul, 153-786, South Korea

    Keyong Ho Lee & Sujeong Kim

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  1. Hee-Jeong Cho
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  2. Soondong Lee
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Correspondence to Yu-Kyoung Oh.

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Cho, HJ., Lee, S., Im, S. et al. Preclinical Pharmacokinetics and Biodistribution of Human Papillomavirus DNA Vaccine Delivered in Human Endogenous Retrovirus Envelope-Coated Baculovirus Vector. Pharm Res 29, 585–593 (2012). https://doi.org/10.1007/s11095-011-0598-z

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  • DOI: https://doi.org/10.1007/s11095-011-0598-z

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