Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.
A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nA...
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Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009624&type=printable |
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| author | Fangping Cai Wei-Hung Chen Weimin Wu Julia A Jones Misook Choe Neelakshi Gohain Xiaoying Shen Celia LaBranche Amanda Eaton Laura Sutherland Esther M Lee Giovanna E Hernandez Nelson R Wu Richard Scearce Michael S Seaman M Anthony Moody Sampa Santra Kevin Wiehe Georgia D Tomaras Kshitij Wagh Bette Korber Mattia Bonsignori David C Montefiori Barton F Haynes Natalia de Val M Gordon Joyce Kevin O Saunders |
| author_facet | Fangping Cai Wei-Hung Chen Weimin Wu Julia A Jones Misook Choe Neelakshi Gohain Xiaoying Shen Celia LaBranche Amanda Eaton Laura Sutherland Esther M Lee Giovanna E Hernandez Nelson R Wu Richard Scearce Michael S Seaman M Anthony Moody Sampa Santra Kevin Wiehe Georgia D Tomaras Kshitij Wagh Bette Korber Mattia Bonsignori David C Montefiori Barton F Haynes Natalia de Val M Gordon Joyce Kevin O Saunders |
| author_sort | Fangping Cai |
| collection | DOAJ |
| description | A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes. |
| format | Article |
| id | doaj-art-49af7daf7eef4bd3a19720f1036c1e68 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-49af7daf7eef4bd3a19720f1036c1e682025-08-20T03:25:19ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-06-01176e100962410.1371/journal.ppat.1009624Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.Fangping CaiWei-Hung ChenWeimin WuJulia A JonesMisook ChoeNeelakshi GohainXiaoying ShenCelia LaBrancheAmanda EatonLaura SutherlandEsther M LeeGiovanna E HernandezNelson R WuRichard ScearceMichael S SeamanM Anthony MoodySampa SantraKevin WieheGeorgia D TomarasKshitij WaghBette KorberMattia BonsignoriDavid C MontefioriBarton F HaynesNatalia de ValM Gordon JoyceKevin O SaundersA primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009624&type=printable |
| spellingShingle | Fangping Cai Wei-Hung Chen Weimin Wu Julia A Jones Misook Choe Neelakshi Gohain Xiaoying Shen Celia LaBranche Amanda Eaton Laura Sutherland Esther M Lee Giovanna E Hernandez Nelson R Wu Richard Scearce Michael S Seaman M Anthony Moody Sampa Santra Kevin Wiehe Georgia D Tomaras Kshitij Wagh Bette Korber Mattia Bonsignori David C Montefiori Barton F Haynes Natalia de Val M Gordon Joyce Kevin O Saunders Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. PLoS Pathogens |
| title | Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. |
| title_full | Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. |
| title_fullStr | Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. |
| title_full_unstemmed | Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. |
| title_short | Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates. |
| title_sort | structural and genetic convergence of hiv 1 neutralizing antibodies in vaccinated non human primates |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1009624&type=printable |
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