التفاصيل البيبلوغرافية
| العنوان: |
Live-virus exposure of vaccine-protected macaques alters the anti-HIV-1 antibody repertoire in the absence of viremia |
| المؤلفون: |
Bachler, Barbara C, Humbert, Michael, Lakhashe, Samir K, Rasmussen, Robert A, Ruprecht, Ruth M |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2013 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
Macaque model, Recombinant protein vaccine, Heterologous R5 SHIV clade C challenge, Complete protection, Subtractive peptide phage display, V3 crown, Boosting of vaccine-induced Ab titers after multiple challenges, Neo-antigen reactivity |
| الوصف: |
Background We addressed the question whether live-virus challenges could alter vaccine-induced antibody (Ab) responses in vaccinated rhesus macaques (RMs) that completely resisted repeated exposures to R5-tropic simian-human immunodeficiency viruses encoding heterologous HIV clade C envelopes (SHIV-Cs). Results We examined the Ab responses in aviremic RMs that had been immunized with a multi-component protein vaccine (multimeric HIV-1 gp160, HIV-1 Tat and SIV Gag-Pol particles) and compared anti-Env plasma Ab titers before and after repeated live-virus exposures. Although no viremia was ever detected in these animals, they showed significant increases in anti-gp140 Ab titers after they had encountered live SHIVs. When we investigated the dynamics of anti-Env Ab titers during the immunization and challenge phases further, we detected the expected, vaccine-induced increases of Ab responses about two weeks after the last protein immunization. Remarkably, these titers kept rising during the repeated virus challenges, although no viremia resulted. In contrast, in vaccinated RMs that were not exposed to virus, anti-gp140 Ab titers declined after the peak seen two weeks after the last immunization. These data suggest boosting of pre-existing, vaccine-induced Ab responses as a consequence of repeated live-virus exposures. Next, we screened polyclonal plasma samples from two of the completely protected vaccinees by peptide phage display and designed a strategy that selects for recombinant phages recognized only by Abs present after – but not before – any SHIV challenge. With this “subtractive biopanning” approach, we isolated V3 mimotopes that were only recognized after the animals had been exposed to live virus. By detailed epitope mapping of such anti-V3 Ab responses, we showed that the challenges not only boosted pre-existing binding and neutralizing Ab titers, but also induced Abs targeting neo-antigens presented by the heterologous challenge virus. Conclusions Anti-Env Ab responses induced by recombinant ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| Relation: |
http://www.retrovirology.com/content/10/1/63 |
| الاتاحة: |
http://www.retrovirology.com/content/10/1/63 |
| Rights: |
Copyright 2013 Bachler et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.64D72907 |
| قاعدة البيانات: |
BASE |