Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual

Krebs, Shelly J.; Kwon, Young D.; Schramm, Chaim A.; Law, William H.; Donofrio, Gina; Zhou, Kenneth H.; Gift, Syna; Dussupt, Vincent; Georgiev, Ivelin S.; Schätzle, Sebastian; McDaniel, Jonathan R.; Lai, Yen-Ting; Sastry, Mallika; Zhang, Baoshan; Jarosinski, Marissa C.; Ransier, Amy; Chenine, Agnes L.; Asokan, Mangaiarkarasi; Bailer, Robert T.; Bose, Meera; Cagigi, Alberto; Cale, Evan M.; Chuang, Gwo-Yu; Darko, Samuel; Driscoll, Jefferson I.; Druz, Aliaksandr; Gorman, Jason; Laboune, Farida; Louder, Mark K.; McKee, Krisha; Mendez, Letzibeth; Moody, M. Anthony; O’Sullivan, Anne Marie; Owen, Christopher; Peng, Dongjun; Rawi, Reda; Sanders-Buell, Eric; Shen, Chen-Hsiang; Shiakolas, Andrea R.; Stephens, Tyler; Tsybovsky, Yaroslav; Tucker, Courtney; Verardi, Raffaello; Wang, Keyun; Zhou, Jing; Zhou, Tongqing; Georgiou, George; Alam, S. Munir; Haynes, Barton F.; Rolland, Morgane; Matyas, Gary R.; Polonis, Victoria R.; McDermott, Adrian B.; Douek, Daniel C.; Shapiro, Lawrence; Tovanabutra, Sodsai; Michael, Nelson L.; Mascola, John R.; Robb, Merlin L.; Kwong, Peter D.; Doria-Rose, Nicole A.

doi:10.1016/j.immuni.2019.02.008

Title: Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual

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Abstract

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

Authors:: Krebs, Shelly J.; Kwon, Young D.; Schramm, Chaim A.; Law, William H.; Donofrio, Gina; Zhou, Kenneth H.; Gift, Syna; Dussupt, Vincent; Georgiev, Ivelin S.; Schätzle, Sebastian; McDaniel, Jonathan R.; Lai, Yen-Ting; Sastry, Mallika; Zhang, Baoshan; Jarosinski, Marissa C.; Ransier, Amy; Chenine, Agnes L.; Asokan, Mangaiarkarasi; Bailer, Robert T.; Bose, Meera more »« less

Publication Date:: Fri Mar 01 00:00:00 EST 2019

Research Org.:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

OSTI Identifier:: 1605457

Alternate Identifier(s):: OSTI ID: 1836705

Grant/Contract Number:: W-31-109-Eng-38

Resource Type:: Published Article

Journal Name:: Immunity

Additional Journal Information:: Journal Name: Immunity Journal Volume: 50 Journal Issue: 3; Journal ID: ISSN 1074-7613

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; HIV envelope; neutralizing antibody; next-generation sequencing

Citation Formats


                    Krebs, Shelly J., Kwon, Young D., Schramm, Chaim A., Law, William H., Donofrio, Gina, Zhou, Kenneth H., Gift, Syna, Dussupt, Vincent, Georgiev, Ivelin S., Schätzle, Sebastian, McDaniel, Jonathan R., Lai, Yen-Ting, Sastry, Mallika, Zhang, Baoshan, Jarosinski, Marissa C., Ransier, Amy, Chenine, Agnes L., Asokan, Mangaiarkarasi, Bailer, Robert T., Bose, Meera, Cagigi, Alberto, Cale, Evan M., Chuang, Gwo-Yu, Darko, Samuel, Driscoll, Jefferson I., Druz, Aliaksandr, Gorman, Jason, Laboune, Farida, Louder, Mark K., McKee, Krisha, Mendez, Letzibeth, Moody, M. Anthony, O’Sullivan, Anne Marie, Owen, Christopher, Peng, Dongjun, Rawi, Reda, Sanders-Buell, Eric, Shen, Chen-Hsiang, Shiakolas, Andrea R., Stephens, Tyler, Tsybovsky, Yaroslav, Tucker, Courtney, Verardi, Raffaello, Wang, Keyun, Zhou, Jing, Zhou, Tongqing, Georgiou, George, Alam, S. Munir, Haynes, Barton F., Rolland, Morgane, Matyas, Gary R., Polonis, Victoria R., McDermott, Adrian B., Douek, Daniel C., Shapiro, Lawrence, Tovanabutra, Sodsai, Michael, Nelson L., Mascola, John R., Robb, Merlin L., Kwong, Peter D., and Doria-Rose, Nicole A. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.  United States: N. p., 2019. 
Web.  doi:10.1016/j.immuni.2019.02.008.

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                    Krebs, Shelly J., Kwon, Young D., Schramm, Chaim A., Law, William H., Donofrio, Gina, Zhou, Kenneth H., Gift, Syna, Dussupt, Vincent, Georgiev, Ivelin S., Schätzle, Sebastian, McDaniel, Jonathan R., Lai, Yen-Ting, Sastry, Mallika, Zhang, Baoshan, Jarosinski, Marissa C., Ransier, Amy, Chenine, Agnes L., Asokan, Mangaiarkarasi, Bailer, Robert T., Bose, Meera, Cagigi, Alberto, Cale, Evan M., Chuang, Gwo-Yu, Darko, Samuel, Driscoll, Jefferson I., Druz, Aliaksandr, Gorman, Jason, Laboune, Farida, Louder, Mark K., McKee, Krisha, Mendez, Letzibeth, Moody, M. Anthony, O’Sullivan, Anne Marie, Owen, Christopher, Peng, Dongjun, Rawi, Reda, Sanders-Buell, Eric, Shen, Chen-Hsiang, Shiakolas, Andrea R., Stephens, Tyler, Tsybovsky, Yaroslav, Tucker, Courtney, Verardi, Raffaello, Wang, Keyun, Zhou, Jing, Zhou, Tongqing, Georgiou, George, Alam, S. Munir, Haynes, Barton F., Rolland, Morgane, Matyas, Gary R., Polonis, Victoria R., McDermott, Adrian B., Douek, Daniel C., Shapiro, Lawrence, Tovanabutra, Sodsai, Michael, Nelson L., Mascola, John R., Robb, Merlin L., Kwong, Peter D., & Doria-Rose, Nicole A. Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.  United States.  https://doi.org/10.1016/j.immuni.2019.02.008

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                    Krebs, Shelly J., Kwon, Young D., Schramm, Chaim A., Law, William H., Donofrio, Gina, Zhou, Kenneth H., Gift, Syna, Dussupt, Vincent, Georgiev, Ivelin S., Schätzle, Sebastian, McDaniel, Jonathan R., Lai, Yen-Ting, Sastry, Mallika, Zhang, Baoshan, Jarosinski, Marissa C., Ransier, Amy, Chenine, Agnes L., Asokan, Mangaiarkarasi, Bailer, Robert T., Bose, Meera, Cagigi, Alberto, Cale, Evan M., Chuang, Gwo-Yu, Darko, Samuel, Driscoll, Jefferson I., Druz, Aliaksandr, Gorman, Jason, Laboune, Farida, Louder, Mark K., McKee, Krisha, Mendez, Letzibeth, Moody, M. Anthony, O’Sullivan, Anne Marie, Owen, Christopher, Peng, Dongjun, Rawi, Reda, Sanders-Buell, Eric, Shen, Chen-Hsiang, Shiakolas, Andrea R., Stephens, Tyler, Tsybovsky, Yaroslav, Tucker, Courtney, Verardi, Raffaello, Wang, Keyun, Zhou, Jing, Zhou, Tongqing, Georgiou, George, Alam, S. Munir, Haynes, Barton F., Rolland, Morgane, Matyas, Gary R., Polonis, Victoria R., McDermott, Adrian B., Douek, Daniel C., Shapiro, Lawrence, Tovanabutra, Sodsai, Michael, Nelson L., Mascola, John R., Robb, Merlin L., Kwong, Peter D., and Doria-Rose, Nicole A. Fri .  
"Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual".  United States.  https://doi.org/10.1016/j.immuni.2019.02.008.

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@article{osti_1605457,

  title        = {Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual},

  author       = {Krebs, Shelly J. and Kwon, Young D. and Schramm, Chaim A. and Law, William H. and Donofrio, Gina and Zhou, Kenneth H. and Gift, Syna and Dussupt, Vincent and Georgiev, Ivelin S. and Schätzle, Sebastian and McDaniel, Jonathan R. and Lai, Yen-Ting and Sastry, Mallika and Zhang, Baoshan and Jarosinski, Marissa C. and Ransier, Amy and Chenine, Agnes L. and Asokan, Mangaiarkarasi and Bailer, Robert T. and Bose, Meera and Cagigi, Alberto and Cale, Evan M. and Chuang, Gwo-Yu and Darko, Samuel and Driscoll, Jefferson I. and Druz, Aliaksandr and Gorman, Jason and Laboune, Farida and Louder, Mark K. and McKee, Krisha and Mendez, Letzibeth and Moody, M. Anthony and O’Sullivan, Anne Marie and Owen, Christopher and Peng, Dongjun and Rawi, Reda and Sanders-Buell, Eric and Shen, Chen-Hsiang and Shiakolas, Andrea R. and Stephens, Tyler and Tsybovsky, Yaroslav and Tucker, Courtney and Verardi, Raffaello and Wang, Keyun and Zhou, Jing and Zhou, Tongqing and Georgiou, George and Alam, S. Munir and Haynes, Barton F. and Rolland, Morgane and Matyas, Gary R. and Polonis, Victoria R. and McDermott, Adrian B. and Douek, Daniel C. and Shapiro, Lawrence and Tovanabutra, Sodsai and Michael, Nelson L. and Mascola, John R. and Robb, Merlin L. and Kwong, Peter D. and Doria-Rose, Nicole A.},

  abstractNote = {Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.},

  doi          = {10.1016/j.immuni.2019.02.008},

  journal      = {Immunity},

  number       = 3,

  volume       = 50,

  place        = {United States},

  year         = {Fri Mar 01 00:00:00 EST 2019},

  month        = {Fri Mar 01 00:00:00 EST 2019}

}

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