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<p>Developing an effective human immunodeficiency virus (HIV) vaccine remains challenging due to difficulties to induce antibodies that neutralize the wide range of HIV-variants. Native-like HIV envelope (Env) trimers in a closed conformation represent promising immunogens. We evaluated the immunogenicity of the chimeric vesicular stomatitis virus-based vector VSV-GP encoding clade C membrane-tethered native-like trimers in heterologous prime/boost combinations with autologous protein. Infected cells displayed high levels of native-like trimers on the surface in a favorable conformation and native-like trimers were also efficiently incorporated into VSV-GP particles. Heterologous vector/protein immunizations outperformed homologous vector regimens, regardless of administration order. In rabbits, these regimens elicited Tier 1 and autologous Tier 2 neutralizing antibodies. Tier 2 neutralization was restricted to pseudoviruses matching the engineered Env-immunogen, with no cross-neutralization of parental Env-variants. Our findings support the use of VSV-GP as a potent platform for displaying native-like Env-trimers and highlight its potential in prime-boost strategies for HIV vaccine development.</p>

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Heterologous combinations of VSV-GP and native-like trimers elicit autologous Tier 2 HIV antibodies in rabbits

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月15日

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  • Frederik Radvan,
  • Alexandra Hauser,
  • Li-Yun Lin,
  • Sarah Wilmschen-Tober,
  • Marion Schaber,
  • Marta Bermejo-Jambrina,
  • Tariq Oluwakunmi Agbabiaka,
  • David Peterhoff,
  • Lydia Riepler,
  • Nadja Mendrzyk,
  • Anja Beierfuß,
  • Cornelia Speth,
  • Christiane Moog,
  • Dorothee von Laer,
  • Ralf Wagner,
  • Janine Kimpel

摘要

Developing an effective human immunodeficiency virus (HIV) vaccine remains challenging due to difficulties to induce antibodies that neutralize the wide range of HIV-variants. Native-like HIV envelope (Env) trimers in a closed conformation represent promising immunogens. We evaluated the immunogenicity of the chimeric vesicular stomatitis virus-based vector VSV-GP encoding clade C membrane-tethered native-like trimers in heterologous prime/boost combinations with autologous protein. Infected cells displayed high levels of native-like trimers on the surface in a favorable conformation and native-like trimers were also efficiently incorporated into VSV-GP particles. Heterologous vector/protein immunizations outperformed homologous vector regimens, regardless of administration order. In rabbits, these regimens elicited Tier 1 and autologous Tier 2 neutralizing antibodies. Tier 2 neutralization was restricted to pseudoviruses matching the engineered Env-immunogen, with no cross-neutralization of parental Env-variants. Our findings support the use of VSV-GP as a potent platform for displaying native-like Env-trimers and highlight its potential in prime-boost strategies for HIV vaccine development.