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

Résumé fourni par la source

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.

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