Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates

Pauthner, M. G.; Nkolola, J. P.; Havenar-Daughton, C.; Murrell, B.; Reiss, S. M.; Bastidas, R.; Prevost, J.; Nedellec, R.; von Bredow, B.; Abbink, P.; Cottrell, C. A.; Kulp, D. W.; Tokatlian, T.; Nogal, B.; Bianchi, M.; Li, H.; Lee, J. H.; Butera, S. T.; Evans, D. T.; Hangartner, L.; Finzi, A.; Wilson, I. A.; Wyatt, R. T.; Irvine, D. J.; Schief, W. R.; Ward, A. B.; Sanders, R. W.; Crotty, S.; Shaw, G. M.; Barouch, D. H.; Burton, D. R.

doi:10.1101/454769

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bioRxiv · 10.1101/454769

Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates

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Abstract

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (Tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection following vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers from the BG505 HIV isolate. Repeat intrarectal challenge with homologous Tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. In contrast, high-titer animals demonstrated protection that was gradually lost as nAb titers waned over weeks to months. From these results, we determined that an autologous serum ID50 nAb titer of ~1:500 was required to afford over 90% protection from medium-dose SHIV infection. We further identified autologous nAb titers, but not ADCC or T cell activity, as strong correlates of protection. These results provide proof-of-concept that Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing Tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

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Pauthner, M. G., Nkolola, J. P., Havenar-Daughton, C., Murrell, B., Reiss, S. M., Bastidas, R., Prevost, J., Nedellec, R., von Bredow, B., Abbink, P., Cottrell, C. A., Kulp, D. W., Tokatlian, T., Nogal, B., Bianchi, M., Li, H., Lee, J. H., Butera, S. T., Evans, D. T., Hangartner, L., Finzi, A., Wilson, I. A., Wyatt, R. T., Irvine, D. J., Schief, W. R., Ward, A. B., Sanders, R. W., Crotty, S., Shaw, G. M., Barouch, D. H., Burton, D. R.. 2018-10-29. Vaccine-induced protection from homologous Tier 2 simian-human immunodeficiency virus challenge in nonhuman primates. https://doi.org/10.1101/454769

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