Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context
Summary: Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection. Methods: Healthy adult volun...
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Elsevier
2025-02-01
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| author | Katrina M. Pollock Hannah M. Cheeseman Leon R. McFarlane Suzanne Day Monica Tolazzi Hannah L. Turner Jennifer Joypooranachandran Katsiaryna Shramko Stefania Dispinseri Philipp Mundsperger Ilja Bontjer Nana-Marie Lemm Sofia Coelho Maniola Tanaka Tom Cole Bette Korber Dietmar Katinger Quentin J. Sattentau Andrew B. Ward Gabriella Scarlatti Rogier W. Sanders Robin J. Shattock |
| author_facet | Katrina M. Pollock Hannah M. Cheeseman Leon R. McFarlane Suzanne Day Monica Tolazzi Hannah L. Turner Jennifer Joypooranachandran Katsiaryna Shramko Stefania Dispinseri Philipp Mundsperger Ilja Bontjer Nana-Marie Lemm Sofia Coelho Maniola Tanaka Tom Cole Bette Korber Dietmar Katinger Quentin J. Sattentau Andrew B. Ward Gabriella Scarlatti Rogier W. Sanders Robin J. Shattock |
| author_sort | Katrina M. Pollock |
| collection | DOAJ |
| description | Summary: Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection. Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.2). All immunogens were co-formulated with liposomal Monophosphoryl-Lipid A (MPLA) adjuvant, and volunteers were followed up for 28 days post final Mosaic booster injection. Participants gave written informed consent to join the study. The study is registered on ClinicalTrials.gov ID NCT03816137. Findings: Fifty-one participants (men n = 23 and women n = 28) aged 18–55 were enrolled. The seroconversion rate against Env was 100% with all participants having measurable anti-Env IgG antibodies after their second injection and throughout the study. Neutralisation was detected against the ConM pseudovirus in sera of those who had received both ConM and ConS immunogens. However, this activity was limited in breadth and was neither boosted nor broadened in those receiving the Mos3.1 and Mos3.2 immunogens. Neutralising antibody function correlated with binding to V1/V3 and V5 epitopes and peaked after the third injection. Interpretation: Rationally designed prefusion-stabilised native-like Env trimers are robustly immunogenic in a prime-boost schedule. When given alone they are insufficient to induce neutralising antibody titres of significant breadth, but they represent potentially valuable polishing immunogens after germline-targeting. Funding: European Aids Vaccine initiative (EAVI2020) received funding from EU Horizon 2020, grant number 681137. Structural studies were supported by the Bill and Melinda Gates Foundation (INV-002916). |
| format | Article |
| id | doaj-art-cf19eba3cf1d49198575d28427122808 |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | EBioMedicine |
| spelling | doaj-art-cf19eba3cf1d49198575d284271228082025-01-04T04:56:32ZengElsevierEBioMedicine2352-39642025-02-01112105544Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in contextKatrina M. Pollock0Hannah M. Cheeseman1Leon R. McFarlane2Suzanne Day3Monica Tolazzi4Hannah L. Turner5Jennifer Joypooranachandran6Katsiaryna Shramko7Stefania Dispinseri8Philipp Mundsperger9Ilja Bontjer10Nana-Marie Lemm11Sofia Coelho12Maniola Tanaka13Tom Cole14Bette Korber15Dietmar Katinger16Quentin J. Sattentau17Andrew B. Ward18Gabriella Scarlatti19Rogier W. Sanders20Robin J. Shattock21Imperial College London, Department of Infectious Disease, UK; NIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKImperial College London, Department of Infectious Disease, UKImperial College London, Department of Infectious Disease, UKImperial College London, Department of Infectious Disease, UKViral Evolution and Transmission Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USAImperial College London, Department of Infectious Disease, UKImperial College London, Department of Infectious Disease, UKViral Evolution and Transmission Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, ItalyPolymun Scientific Immunbiologische Forschung GmbH, Klosterneuburg, AustriaDepartment of Medical Microbiology, Academic Medical Centre University of Amsterdam, Amsterdam, the NetherlandsNIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKNIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKNIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKNIHR Imperial Clinical Research Facility and NIHR Imperial Biomedical Research Centre, London, UKNew Mexico Consortium, Los Alamos, NM, USAPolymun Scientific Immunbiologische Forschung GmbH, Klosterneuburg, AustriaThe Sir William Dunn School of Pathology, The University of Oxford, Oxford, UKDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USAViral Evolution and Transmission Unit, Division of Immunology, Transplantation, and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Medical Microbiology, Academic Medical Centre University of Amsterdam, Amsterdam, the NetherlandsImperial College London, Department of Infectious Disease, UK; Corresponding author.Summary: Background: We report findings from an experimental medicine study of rationally designed prefusion stabilised native-like HIV envelope glycoprotein (Env) immunogens, representative of global circulating strains, delivered by sequential intramuscular injection. Methods: Healthy adult volunteers were enrolled into one of five groups (A to E) each receiving a different schedule of one of two consensus Env immunogens (ConM SOSIP, ConS UFO, either unmodified or stabilised by chemical cross-linking, followed by a boost with two mosaic Env immunogens (Mos3.1 and Mos3.2). All immunogens were co-formulated with liposomal Monophosphoryl-Lipid A (MPLA) adjuvant, and volunteers were followed up for 28 days post final Mosaic booster injection. Participants gave written informed consent to join the study. The study is registered on ClinicalTrials.gov ID NCT03816137. Findings: Fifty-one participants (men n = 23 and women n = 28) aged 18–55 were enrolled. The seroconversion rate against Env was 100% with all participants having measurable anti-Env IgG antibodies after their second injection and throughout the study. Neutralisation was detected against the ConM pseudovirus in sera of those who had received both ConM and ConS immunogens. However, this activity was limited in breadth and was neither boosted nor broadened in those receiving the Mos3.1 and Mos3.2 immunogens. Neutralising antibody function correlated with binding to V1/V3 and V5 epitopes and peaked after the third injection. Interpretation: Rationally designed prefusion-stabilised native-like Env trimers are robustly immunogenic in a prime-boost schedule. When given alone they are insufficient to induce neutralising antibody titres of significant breadth, but they represent potentially valuable polishing immunogens after germline-targeting. Funding: European Aids Vaccine initiative (EAVI2020) received funding from EU Horizon 2020, grant number 681137. Structural studies were supported by the Bill and Melinda Gates Foundation (INV-002916).http://www.sciencedirect.com/science/article/pii/S2352396424005802HIV envelopeExperimental medicineHIV-1PrefusionTrimerVaccine |
| spellingShingle | Katrina M. Pollock Hannah M. Cheeseman Leon R. McFarlane Suzanne Day Monica Tolazzi Hannah L. Turner Jennifer Joypooranachandran Katsiaryna Shramko Stefania Dispinseri Philipp Mundsperger Ilja Bontjer Nana-Marie Lemm Sofia Coelho Maniola Tanaka Tom Cole Bette Korber Dietmar Katinger Quentin J. Sattentau Andrew B. Ward Gabriella Scarlatti Rogier W. Sanders Robin J. Shattock Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context EBioMedicine HIV envelope Experimental medicine HIV-1 Prefusion Trimer Vaccine |
| title | Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context |
| title_full | Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context |
| title_fullStr | Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context |
| title_full_unstemmed | Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context |
| title_short | Experimental medicine study with stabilised native-like HIV-1 Env immunogens drives long-term antibody responses, but lacks neutralising breadthResearch in context |
| title_sort | experimental medicine study with stabilised native like hiv 1 env immunogens drives long term antibody responses but lacks neutralising breadthresearch in context |
| topic | HIV envelope Experimental medicine HIV-1 Prefusion Trimer Vaccine |
| url | http://www.sciencedirect.com/science/article/pii/S2352396424005802 |
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