Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency
JournalJournal of virology
PublisherAmerican Society for Microbiology
MetadataShow full item record
AbstractInduction of protective antibodies is a critical goal of HIV-1 vaccine development. One strategy is to induce nonneutralizing antibodies (NNAbs) that kill virus-infected cells, as these antibody specificities have been implicated in slowing HIV-1 disease progression and in protection. HIV-1 Env constant region 1 and 2 (C1C2) monoclonal antibodies (MAbs) frequently mediate potent antibody-dependent cellular cytotoxicity (ADCC), making them an important vaccine target. Here, we explore the effect of delayed and repetitive boosting of RV144 vaccine recipients with AIDSVAX B/E on the C1C2-specific MAb repertoire. It was found that boosting increased clonal lineage-specific ADCC breadth and potency. A ligand crystal structure of a vaccine-induced broad and potent ADCC-mediating C1C2-specific MAb showed that it bound a highly conserved Env gp120 epitope. Thus, boosting to affinity mature these types of IgG C1C2-specific antibody responses may be one method by which to make an improved HIV vaccine with higher efficacy than that seen in the RV144 trial.IMPORTANCE Over one million people become infected with HIV-1 each year, making the development of an efficacious HIV-1 vaccine an important unmet medical need. The RV144 human HIV-1 vaccine regimen is the only HIV-1 clinical trial to date to demonstrate vaccine efficacy. An area of focus has been on identifying ways by which to improve upon RV144 vaccine efficacy. The RV305 HIV-1 vaccine regimen was a follow-up boost of RV144 vaccine recipients that occurred 6 to 8 years after the conclusion of RV144. Our study focused on the effect of delayed boosting in humans on the vaccine-induced Env constant region 1 and 2 (C1C2)-specific antibody repertoire. It was found that boosting with an HIV-1 Env vaccine increased C1C2-specific antibody-dependent cellular cytotoxicity potency and breadth. Copyright 2020 Easterhoff et al.
SponsorsThis work was primarily supported by Collaboration for AIDS Vaccine Discovery grant OPP1114721 from the Bill & Melinda Gates Foundation to B.F.H., NIH grants NIAID R01 AI116274 and R01 AI129769 to M.P. and NIAID P01 AI120756 to G.D.T., and Henry M. Jackson Foundation for the Advancement of Military Medicine grant number 829295 to B.F.H.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85078869916&doi=10.1128%2fJVI.01120-19&partnerID=40&md5=240c6ae4f68cd97707e84c80a780f4ea; http://hdl.handle.net/10713/11987
- Recognition Patterns of the C1/C2 Epitopes Involved in Fc-Mediated Response in HIV-1 Natural Infection and the RV114 Vaccine Trial.
- Authors: Tolbert WD, Van V, Sherburn R, Tuyishime M, Yan F, Nguyen DN, Stanfield-Oakley S, Easterhoff D, Bonsignori M, Haynes BF, Moody MA, Ray K, Ferrari G, Lewis GK, Pazgier M
- Issue date: 2020 Jun 30
- A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques.
- Authors: Jones AT, Chamcha V, Kesavardhana S, Shen X, Beaumont D, Das R, Wyatt LS, LaBranche CC, Stanfield-Oakley S, Ferrari G, Montefiori DC, Moss B, Tomaras GD, Varadarajan R, Amara RR
- Issue date: 2018 Mar 1
- Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.
- Authors: Easterhoff D, Moody MA, Fera D, Cheng H, Ackerman M, Wiehe K, Saunders KO, Pollara J, Vandergrift N, Parks R, Kim J, Michael NL, O'Connell RJ, Excler JL, Robb ML, Vasan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Kepler TB, Alam SM, Liao HX, Ferrari G, Seaman MS, Montefiori DC, Tomaras GD, Harrison SC, Haynes BF
- Issue date: 2017 Feb
- Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001.
- Authors: Costa MR, Pollara J, Edwards RW, Seaman MS, Gorny MK, Montefiori DC, Liao HX, Ferrari G, Lu S, Wang S
- Issue date: 2016 Nov 15
- HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.
- Authors: Easterhoff D, Pollara J, Luo K, Janus B, Gohain N, Williams LD, Tay MZ, Monroe A, Peachman K, Choe M, Min S, Lusso P, Zhang P, Go EP, Desaire H, Bonsignori M, Hwang KK, Beck C, Kakalis M, O'Connell RJ, Vasan S, Kim JH, Michael NL, Excler JL, Robb ML, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Wiehe K, Saunders KO, Montefiori DC, Tomaras GD, Moody MA, Arthos J, Rao M, Joyce MG, Ofek G, Ferrari G, Haynes BF
- Issue date: 2020 Jan 30