Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.
Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT0...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5922559?pdf=render |
| _version_ | 1818864302027702272 |
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| author | Siriwat Akapirat Chitraporn Karnasuta Sandhya Vasan Supachai Rerks-Ngarm Punnee Pitisuttithum Sirinan Madnote Hathairat Savadsuk Surawach Rittiroongrad Jiraporn Puangkaew Sanjay Phogat James Tartaglia Faruk Sinangil Mark S de Souza Jean-Louis Excler Jerome H Kim Merlin L Robb Nelson L Michael Viseth Ngauy Robert J O'Connell Nicos Karasavvas RV305 Study Group |
| author_facet | Siriwat Akapirat Chitraporn Karnasuta Sandhya Vasan Supachai Rerks-Ngarm Punnee Pitisuttithum Sirinan Madnote Hathairat Savadsuk Surawach Rittiroongrad Jiraporn Puangkaew Sanjay Phogat James Tartaglia Faruk Sinangil Mark S de Souza Jean-Louis Excler Jerome H Kim Merlin L Robb Nelson L Michael Viseth Ngauy Robert J O'Connell Nicos Karasavvas RV305 Study Group |
| author_sort | Siriwat Akapirat |
| collection | DOAJ |
| description | Sexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold) and SP (2 fold) two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma IgG levels (p<0.001). Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition. |
| first_indexed | 2024-12-19T10:29:29Z |
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| id | doaj.art-b6a6cce028b540d6b3b05c44c133477e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T10:29:29Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b6a6cce028b540d6b3b05c44c133477e2022-12-21T20:25:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019639710.1371/journal.pone.0196397Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations.Siriwat AkapiratChitraporn KarnasutaSandhya VasanSupachai Rerks-NgarmPunnee PitisuttithumSirinan MadnoteHathairat SavadsukSurawach RittiroongradJiraporn PuangkaewSanjay PhogatJames TartagliaFaruk SinangilMark S de SouzaJean-Louis ExclerJerome H KimMerlin L RobbNelson L MichaelViseth NgauyRobert J O'ConnellNicos KarasavvasRV305 Study GroupSexual transmission is the principal driver of the human immunodeficiency virus (HIV) pandemic. Understanding HIV vaccine-induced immune responses at mucosal surfaces can generate hypotheses regarding mechanisms of protection, and may influence vaccine development. The RV144 (ClinicalTrials.gov NCT00223080) efficacy trial showed protection against HIV infections but mucosal samples were not collected, therefore, the contribution of mucosal antibodies to preventing HIV-1 acquisition is unknown. Here, we report the generation, magnitude and persistence of antibody responses to recombinant gp120 envelope and antigens including variable one and two loop scaffold antigens (gp70V1V2) previously shown to correlate with risk in RV144. We evaluated antibody responses to gp120 A244gD and gp70V1V2 92TH023 (both CRF01_AE) and Case A2 (subtype B) in cervico-vaginal mucus (CVM), seminal plasma (SP) and rectal secretions (RS) from HIV-uninfected RV144 vaccine recipients, who were randomized to receive two late boosts of ALVAC-HIV/AIDSVAX®B/E, AIDSVAX®B/E, or ALVAC-HIV alone at 0 and 6 months. Late vaccine boosting increased IgG geometric mean titers (GMT) to gp120 A244gD in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (28 and 17 fold, respectively), followed by SP and RS. IgG to gp70V1V2 92TH023 increased in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM (11-17 fold) and SP (2 fold) two weeks post first boost. IgG to Case A2 was only detected in AIDSVAX®B/E and ALVAC-HIV/AIDSVAX®B/E CVM. Mucosal IgG to gp120 A244gD (CVM, SP, RS), gp70V1V2 92TH023 (CVM, SP), and Case A2 (CVM) correlated with plasma IgG levels (p<0.001). Although the magnitude of IgG responses declined after boosting, anti-gp120 A244gD IgG responses in CVM persisted for 12 months post final vaccination. Further studies in localization, persistence and magnitude of envelope specific antibodies (IgG and dimeric IgA) in anogenital secretions will help determine their role in preventing mucosal HIV acquisition.http://europepmc.org/articles/PMC5922559?pdf=render |
| spellingShingle | Siriwat Akapirat Chitraporn Karnasuta Sandhya Vasan Supachai Rerks-Ngarm Punnee Pitisuttithum Sirinan Madnote Hathairat Savadsuk Surawach Rittiroongrad Jiraporn Puangkaew Sanjay Phogat James Tartaglia Faruk Sinangil Mark S de Souza Jean-Louis Excler Jerome H Kim Merlin L Robb Nelson L Michael Viseth Ngauy Robert J O'Connell Nicos Karasavvas RV305 Study Group Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. PLoS ONE |
| title | Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. |
| title_full | Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. |
| title_fullStr | Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. |
| title_full_unstemmed | Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. |
| title_short | Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. |
| title_sort | characterization of hiv 1 gp120 antibody specificities induced in anogenital secretions of rv144 vaccine recipients after late boost immunizations |
| url | http://europepmc.org/articles/PMC5922559?pdf=render |
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