V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144.
Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound g...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5498072?pdf=render |
| _version_ | 1818495614585929728 |
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| author | Lautaro G Perez David R Martinez Allan C deCamp Abraham Pinter Phillip W Berman Donald Francis Faruk Sinangil Carter Lee Kelli Greene Hongmei Gao Sorachai Nitayaphan Supachai Rerks-Ngarm Jaranit Kaewkungwal Punnee Pitisuttithum James Tartaglia Robert J O'Connell Merlin L Robb Nelson L Michael Jerome H Kim Peter Gilbert David C Montefiori |
| author_facet | Lautaro G Perez David R Martinez Allan C deCamp Abraham Pinter Phillip W Berman Donald Francis Faruk Sinangil Carter Lee Kelli Greene Hongmei Gao Sorachai Nitayaphan Supachai Rerks-Ngarm Jaranit Kaewkungwal Punnee Pitisuttithum James Tartaglia Robert J O'Connell Merlin L Robb Nelson L Michael Jerome H Kim Peter Gilbert David C Montefiori |
| author_sort | Lautaro G Perez |
| collection | DOAJ |
| description | Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial. |
| first_indexed | 2024-12-10T18:22:59Z |
| format | Article |
| id | doaj.art-c36ea6f861184e5d9675e59626f76437 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T18:22:59Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c36ea6f861184e5d9675e59626f764372022-12-22T01:38:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01127e018072010.1371/journal.pone.0180720V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144.Lautaro G PerezDavid R MartinezAllan C deCampAbraham PinterPhillip W BermanDonald FrancisFaruk SinangilCarter LeeKelli GreeneHongmei GaoSorachai NitayaphanSupachai Rerks-NgarmJaranit KaewkungwalPunnee PitisuttithumJames TartagliaRobert J O'ConnellMerlin L RobbNelson L MichaelJerome H KimPeter GilbertDavid C MontefioriNon-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.http://europepmc.org/articles/PMC5498072?pdf=render |
| spellingShingle | Lautaro G Perez David R Martinez Allan C deCamp Abraham Pinter Phillip W Berman Donald Francis Faruk Sinangil Carter Lee Kelli Greene Hongmei Gao Sorachai Nitayaphan Supachai Rerks-Ngarm Jaranit Kaewkungwal Punnee Pitisuttithum James Tartaglia Robert J O'Connell Merlin L Robb Nelson L Michael Jerome H Kim Peter Gilbert David C Montefiori V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. PLoS ONE |
| title | V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. |
| title_full | V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. |
| title_fullStr | V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. |
| title_full_unstemmed | V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. |
| title_short | V1V2-specific complement activating serum IgG as a correlate of reduced HIV-1 infection risk in RV144. |
| title_sort | v1v2 specific complement activating serum igg as a correlate of reduced hiv 1 infection risk in rv144 |
| url | http://europepmc.org/articles/PMC5498072?pdf=render |
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