Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth

Roark, R. S.; Li, H.; Williams, W. B.; Chug, H.; Mason, R. D.; Gorman, J.; Wang, S.; Lee, F.-H.; Rando, J.; Bonsignori, M.; Hwang, K.-K.; Saunders, K. O.; Wiehe, K.; Moody, M. A.; Hraber, P. T.; Wagh, K.; Giorgi, E. E.; Russell, R. M.; Bibollet-Ruche, F.; Liu, W.; Connell, J.; Smith, A. G.; DeVoto, J.; Murphy, A. I.; Smith, J.; Ding, W.; Zhao, C.; Chohan, N.; Okumura, M.; Rosario, C.; Ding, Y.; Lindemuth, E.; Bauer, A. M.; Bar, K. J.; Ambrozak, D.; Chao, C. W.; Chuang, G.-Y.; Geng, H.; Lin, B. C.; Louder, M. K.; Nguyen, R.; Zhang, B.; Lewis, M. G.; Raymond, D.; Doria-Rose, N. A.; Schramm, C. A

doi:10.1101/2020.08.05.237693

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bioRxiv · 10.1101/2020.08.05.237693

Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth

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Abstract

Neutralizing antibodies elicited by HIV-1 coevolve with viral Envs in distinctive patterns, in some cases acquiring substantial breadth. Here we show that primary HIV-1 Envs, when expressed by simian-human immunodeficiency viruses in rhesus macaques, elicited patterns of Env-antibody coevolution strikingly similar to those in humans. This included conserved immunogenetic, structural and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2-apex mode of recognition like that of human bNAbs PGT145/PCT64-35M. Another rhesus antibody bound the CD4-binding site by CD4 mimicry mirroring human bNAbs 8ANC131/CH235/VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design. One sentence summaryVirus-antibody coevolution in rhesus macaques recapitulates developmental features of human antibodies.

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Roark, R. S., Li, H., Williams, W. B., Chug, H., Mason, R. D., Gorman, J., Wang, S., Lee, F.-H., Rando, J., Bonsignori, M., Hwang, K.-K., Saunders, K. O., Wiehe, K., Moody, M. A., Hraber, P. T., Wagh, K., Giorgi, E. E., Russell, R. M., Bibollet-Ruche, F., Liu, W., Connell, J., Smith, A. G., DeVoto, J., Murphy, A. I., Smith, J., Ding, W., Zhao, C., Chohan, N., Okumura, M., Rosario, C., Ding, Y., Lindemuth, E., Bauer, A. M., Bar, K. J., Ambrozak, D., Chao, C. W., Chuang, G.-Y., Geng, H., Lin, B. C., Louder, M. K., Nguyen, R., Zhang, B., Lewis, M. G., Raymond, D., Doria-Rose, N. A., Schramm, C. A. 2020-08-05. Recapitulation of HIV-1 Env-Antibody Coevolution in Macaques Leading to Neutralization Breadth. https://doi.org/10.1101/2020.08.05.237693

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