Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template

Andrabi, R.; Pallesen, J.; Allen, J.; Song, G.; Zhang, J.; de Val, N.; Gegg, G.; Porter, K.; Su, C.-Y.; Pauthner, M.; Newman, A.; Bouton-Vervelle, H.; Garces, F.; Wilson, I. A.; Crispin, M.; Hahn, B. H.; Haynes, B. F.; Verkoczy, L.; Ward, A. B.; Burton, D. R.

doi:10.1101/459164

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bioRxiv · 10.1101/459164

Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template

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Abstract

Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. Chimpanzee SIV Envelope (Env) shares a single bnAb site, the V2-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Accordingly, we generated a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determined the structure of the MT145K trimer by cryo-EM and showed its architecture was remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knock-in mouse with chimpanzee MT145K trimer induced HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induced responses exhibiting some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs.

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Andrabi, R., Pallesen, J., Allen, J., Song, G., Zhang, J., de Val, N., Gegg, G., Porter, K., Su, C.-Y., Pauthner, M., Newman, A., Bouton-Vervelle, H., Garces, F., Wilson, I. A., Crispin, M., Hahn, B. H., Haynes, B. F., Verkoczy, L., Ward, A. B., Burton, D. R.. 2018-11-01. Chimpanzee SIV Envelope trimer: structure and deployment as an HIV vaccine template. https://doi.org/10.1101/459164

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