TY - JOUR
T1 - Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations
AU - on behalf of The RV305 Study Group
AU - Akapirat, Siriwat
AU - Karnasuta, Chitraporn
AU - Vasan, Sandhya
AU - Rerks-Ngarm, Supachai
AU - Pitisuttithum, Punnee
AU - Madnote, Sirinan
AU - Savadsuk, Hathairat
AU - Rittiroongrad, Surawach
AU - Puangkaew, Jiraporn
AU - Phogat, Sanjay
AU - Tartaglia, James
AU - Sinangil, Faruk
AU - de Souza, Mark S.
AU - Excler, Jean Louis
AU - Kim, Jerome H.
AU - Robb, Merlin L.
AU - Michael, Nelson L.
AU - Ngauy, Viseth
AU - O’Connell, Robert J.
AU - Karasavvas, Nicos
N1 - Funding Information:
This work was supported by the US Army Medical Research and Materiel Command (Military Infectious Diseases Research Program) (cooperative agreements W81XWH-11-2-0174 and W81XWH-07-2-0067 with the Henry M. Jackson Foundation for the Advancement of Military Medicine); the National Institute of Allergy and Infectious Disease (interagency agreement Y1-AI-2642-12 with the US Army Medical Research and Materiel Command and an F31 fellowship), and the Bill & Melinda Gates Foundation (CAVIMC grants OPP1032144 and OP1146996). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder (Sanofi Pasteur and Global Solutions for Infectious Diseases (GSID)) provided support in the form of investigational products and salaries for authors (Sanofi Pasteur: S.P. and J.T.; GSID: F.S.), but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the’authors contributions’ section. Disclaimer: Material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70–25. We gratefully thank the volunteers for their dedication and active participation in this study. We thank Dr. Abraham Pinter for gp70V1V2 scaffold proteins. The RV305 Study Group included the following: Ministry of Public Health: S. R. N., Nakorn Premsri, Narongsak Ekwattanakul, Thanakorn Arunngamwong, Chawetsan Namwat, Prayura Kunasol, Prasert Thongcharoen, and Attaya Limwattanayingyong; Mahidol University: P. P., Jittima Dhitavat, and Benjaluck Phonrat; Center of Excellence for Biomedical and Public Health Informatics: Jaranit Kaewkungwal and Pawinee Jarujareet; Armed Forces Research Institute of Medical Sciences: R. J. O., S. V., N. K., Alexandra Schuetz, Susan Mason, V. N., Nampueng Churikanont, Nongluck Sangnoi, Saowanit Getchalarat, Patricia Morgan, Pornsuk Visudhiphan, M. D. S., S. A., Bessara Nuntapinit, Rapee Trichavaroj, Kirsten S. Smith, and C. K.; Royal Thai Army–Armed Forces Research Institute of Medical Sciences: Sora-chai Nitayaphan and Chirapa Eamsila; US Military HIV Research Program: J. H. K., M. L. R., J. L. E., Jintanat Ananworanich, Silvia Ratto-Kim, N. L. M., Charla Andrews, Robert Gramzinski, Poonam Pegu, and Michael Eller.; US Army Medical Materiel Development Activity: Elizabeth Heger; Emmes Corporation: Don Stablein and Peter Dawson; Global Solutions for Infectious Diseases: F. S., Carter Lee, and D. P. F.; Sanofi Pasteur: J. T., Sanjay Garunathan, S. P., and Carlos DiazGranados.
Publisher Copyright:
© This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2018/4
Y1 - 2018/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046090819&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0196397
DO - 10.1371/journal.pone.0196397
M3 - Article
C2 - 29702672
AN - SCOPUS:85046090819
SN - 1932-6203
VL - 13
JO - PLoS ONE
JF - PLoS ONE
IS - 4
M1 - e0196397
ER -