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@ARTICLE{Zhang:288564,
      author       = {Y. Zhang$^*$ and F. C. Mariz$^*$ and P. Sehr and G.
                      Spagnoli and K. M. Koenig$^*$ and S. Çelikyürekli$^*$ and
                      T. Kreuziger and X. Zhao$^*$ and A. Bolchi and S. Ottonello
                      and M. Müller$^*$},
      title        = {{I}nter-epitope spacer variation within polytopic
                      {L}2-based human papillomavirus antigens affects
                      immunogenicity.},
      journal      = {npj vaccines},
      volume       = {9},
      number       = {1},
      issn         = {2059-0105},
      address      = {[London]},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2024-00410},
      pages        = {44},
      year         = {2024},
      note         = {#EA:F035#LA:F035# /NEU/ #EA:D335#LA:D335#},
      abstract     = {The human papillomavirus minor capsid protein L2 is being
                      extensively explored in pre-clinical studies as an
                      attractive vaccine antigen capable of inducing
                      broad-spectrum prophylactic antibody responses. Recently, we
                      have developed two HPV vaccine antigens - PANHPVAX and
                      CUT-PANHPVAX- both based on heptameric nanoparticle antigens
                      displaying polytopes of the L2 major cross-neutralizing
                      epitopes of eight mucosal and twelve cutaneous HPV types,
                      respectively. Prompted by the variable neutralizing antibody
                      responses against some of the HPV types targeted by the
                      antigens observed in previous studies, here we investigated
                      the influence on immunogenicity of six distinct
                      glycine-proline spacers inserted upstream to a specific L2
                      epitope. We show that spacer variants differentially
                      influence antigen immunogenicity in a mouse model, with the
                      antigen constructs M8merV6 and C12merV6 displaying a
                      superior ability in the induction of neutralizing antibodies
                      as determined by pseudovirus-based neutralization assays
                      (PBNAs). L2-peptide enzyme-linked immunosorbent assay
                      (ELISA) assessments determined the total anti-L2 antibody
                      level for each antigen variant, showing for the majority of
                      sera a correlation with their repective neutralizing
                      antibody level. Surface Plasmon Resonance revealed that L2
                      epitope-specific, neutralizing monoclonal antibodies (mAbs)
                      display distinct avidities to different antigen spacer
                      variants. Furthermore, mAb affinity toward individual spacer
                      variants was well correlated with their neutralizing
                      antibody induction capacity, indicating that the mAb
                      affinity assay predicts L2-based antigen immunogenicity.
                      These observations provide insights on the development and
                      optimization of L2-based HPV vaccines.},
      cin          = {F035 / D335},
      ddc          = {610},
      cid          = {I:(DE-He78)F035-20160331 / I:(DE-He78)D335-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38402256},
      doi          = {10.1038/s41541-024-00832-0},
      url          = {https://inrepo02.dkfz.de/record/288564},
}