Efficiency of HPV 16 L1/E7 DNA immunization: Influence of cellular localization and capsid assembly

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  • Dirk Kuck
  • Christoph Leder
  • Andrea Kern
  • Martin Müller
  • Konrad Piuko
  • Lutz Gissmann
  • Jürgen A. Kleinschmidt
Infections by human papillomaviruses (HPV) are the major cause of uterine cancer in women worldwide. Aiming to develop a combined prophylactic and therapeutic vaccine we have previously demonstrated immunogenicity of chimeric virus-like particles consisting of a C-terminally truncated HPV 16 L1 capsid protein fused to an E7 portion. Here we show that genetic vaccination with a corresponding DNA was inefficient in the induction of a L1-specific prophylactic immune response. DNA immunization with C-terminally truncated HPV 16 L1 genes of different lengths revealed that only short deletions (L1(1-498)) were tolerated for eliciting a humoral immune response against viral capsids. This correlates with the observation that the C-terminal sequences are critical for nuclear localization, capsomere and capsid assembly. However, only the ability of L1 protein to form capsomeres or capsids showed a direct influence on the outcome of the immune response. C-terminal insertion of 60 amino acids of E7 was tolerated in fusion constructs, whereas insertion of full-length E7(1-98) or shuffled E7 (149 aa) completely abolished the humoral immune response. The L1(1-498)/E7(1-60) fusion construct not only induced L1-specific antibodies but also L1- and E7-specific CTL responses after DNA vaccination.
Original languageEnglish
Issue number15
Pages (from-to)2952-2965
Number of pages14
Publication statusPublished - 05.04.2006
Externally publishedYes

Bibliographical note

Funding Information:
We thank Nico Michel and Corinna Klein for help with the ELISPOT assay, Petra Galmbacher for the L1-VLP production and Martin Friedel from the DKFZ animal facility. We are grateful to Harald zur Hausen for his continuous support. J.A.K. and M.M. were supported by grant 10–1912 Kl 1 of the Deutsche Krebshilfe.

    Research areas

  • Biology
  • DNA immunization, Papillomavirus