Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates
E. I. M. M. Reiss,
M. M. van Haaren,
J. van Schooten,
M. A. F. Claireaux,
P. Maisonnasse,
A. Antanasijevic,
J. D. Allen,
I. Bontjer,
J. L. Torres,
W-H Lee,
G. Ozorowski,
N. Vázquez Bernat,
M. Kaduk,
Y. Aldon,
J. A. Burger,
H. Chawla,
A. Aartse,
M. Tolazzi,
H. Gao,
P. Mundsperger,
M. Crispin,
D. C. Montefiori,
G. B. Karlsson Hedestam,
G. Scarlatti,
A. B. Ward,
R. Le Grand,
R. Shattock,
N. Dereuddre-Bosquet,
R. W. Sanders,
M. J. van Gils
Affiliations
E. I. M. M. Reiss
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
M. M. van Haaren
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
J. van Schooten
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
M. A. F. Claireaux
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
P. Maisonnasse
Université Paris-Saclay – CEA - INSERM U1184, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
A. Antanasijevic
Department of Integrative Structural and Computational Biology, Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
J. D. Allen
School of Biological Sciences, University of Southampton
I. Bontjer
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
J. L. Torres
Department of Integrative Structural and Computational Biology, Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
W-H Lee
Department of Integrative Structural and Computational Biology, Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
G. Ozorowski
Department of Integrative Structural and Computational Biology, Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
N. Vázquez Bernat
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
M. Kaduk
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
Y. Aldon
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
J. A. Burger
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
H. Chawla
School of Biological Sciences, University of Southampton
A. Aartse
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
M. Tolazzi
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele
H. Gao
Department of Surgery, Duke University Medical Center
School of Biological Sciences, University of Southampton
D. C. Montefiori
Department of Surgery, Duke University Medical Center
G. B. Karlsson Hedestam
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
G. Scarlatti
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele
A. B. Ward
Department of Integrative Structural and Computational Biology, Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
R. Le Grand
Université Paris-Saclay – CEA - INSERM U1184, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
R. Shattock
Division of Mucosal Infection and Immunity, Department of Medicine, Imperial College of Science, Technology and Medicine
N. Dereuddre-Bosquet
Université Paris-Saclay – CEA - INSERM U1184, Center for Immunology of Viral, Auto-immune, Hematological and Bacterial diseases (IMVA-HB/IDMIT)
R. W. Sanders
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
M. J. van Gils
Amsterdam UMC, location University of Amsterdam, Department of Medical Microbiology and Infection Prevention, Laboratory of Experimental Virology
Abstract The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.
