High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope.
A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized th...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011717&type=printable |
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| author | Rohini Mopuri Sarah Welbourn Tysheena Charles Pooja Ralli-Jain David Rosales Samantha Burton Areeb Aftab Kirti Karunakaran Kathryn Pellegrini William Kilembe Etienne Karita Sandrasegaram Gnanakaran Amit A Upadhyay Steven E Bosinger Cynthia A Derdeyn |
| author_facet | Rohini Mopuri Sarah Welbourn Tysheena Charles Pooja Ralli-Jain David Rosales Samantha Burton Areeb Aftab Kirti Karunakaran Kathryn Pellegrini William Kilembe Etienne Karita Sandrasegaram Gnanakaran Amit A Upadhyay Steven E Bosinger Cynthia A Derdeyn |
| author_sort | Rohini Mopuri |
| collection | DOAJ |
| description | A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages. |
| format | Article |
| id | doaj-art-1134d83f0e044f18b5105af8a940f58d |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2023-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1134d83f0e044f18b5105af8a940f58d2025-08-20T03:12:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742023-10-011910e101171710.1371/journal.ppat.1011717High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope.Rohini MopuriSarah WelbournTysheena CharlesPooja Ralli-JainDavid RosalesSamantha BurtonAreeb AftabKirti KarunakaranKathryn PellegriniWilliam KilembeEtienne KaritaSandrasegaram GnanakaranAmit A UpadhyaySteven E BosingerCynthia A DerdeynA protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011717&type=printable |
| spellingShingle | Rohini Mopuri Sarah Welbourn Tysheena Charles Pooja Ralli-Jain David Rosales Samantha Burton Areeb Aftab Kirti Karunakaran Kathryn Pellegrini William Kilembe Etienne Karita Sandrasegaram Gnanakaran Amit A Upadhyay Steven E Bosinger Cynthia A Derdeyn High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. PLoS Pathogens |
| title | High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. |
| title_full | High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. |
| title_fullStr | High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. |
| title_full_unstemmed | High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. |
| title_short | High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope. |
| title_sort | high throughput analysis of b cell dynamics and neutralizing antibody development during immunization with a novel clade c hiv 1 envelope |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1011717&type=printable |
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