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Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers. / Gallinaro, Alessandra; Pirillo, Maria Franca; Aldon, Yoann; Cecchetti, Serena; Michelini, Zuleika; Tinari, Antonella; Borghi, Martina; Canitano, Andrea; McKay, Paul F.; Bona, Roberta; Vescio, Maria Fenicia; Grasso, Felicia; Blasi, Maria; Baroncelli, Silvia; Scarlatti, Gabriella; LaBranche, Celia; Montefiori, David; Klotman, Mary E.; Sanders, Rogier W.; Shattock, Robin J.; Negri, Donatella; Cara, Andrea.

In: npj Vaccines, Vol. 7, No. 1, 44, 01.12.2022.

Research output: Contribution to journalArticleAcademicpeer-review

Harvard

Gallinaro, A, Pirillo, MF, Aldon, Y, Cecchetti, S, Michelini, Z, Tinari, A, Borghi, M, Canitano, A, McKay, PF, Bona, R, Vescio, MF, Grasso, F, Blasi, M, Baroncelli, S, Scarlatti, G, LaBranche, C, Montefiori, D, Klotman, ME, Sanders, RW, Shattock, RJ, Negri, D & Cara, A 2022, 'Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers', npj Vaccines, vol. 7, no. 1, 44. https://doi.org/10.1038/s41541-022-00465-1

APA

Gallinaro, A., Pirillo, M. F., Aldon, Y., Cecchetti, S., Michelini, Z., Tinari, A., Borghi, M., Canitano, A., McKay, P. F., Bona, R., Vescio, M. F., Grasso, F., Blasi, M., Baroncelli, S., Scarlatti, G., LaBranche, C., Montefiori, D., Klotman, M. E., Sanders, R. W., ... Cara, A. (2022). Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers. npj Vaccines, 7(1), [44]. https://doi.org/10.1038/s41541-022-00465-1

Vancouver

Author

Gallinaro, Alessandra ; Pirillo, Maria Franca ; Aldon, Yoann ; Cecchetti, Serena ; Michelini, Zuleika ; Tinari, Antonella ; Borghi, Martina ; Canitano, Andrea ; McKay, Paul F. ; Bona, Roberta ; Vescio, Maria Fenicia ; Grasso, Felicia ; Blasi, Maria ; Baroncelli, Silvia ; Scarlatti, Gabriella ; LaBranche, Celia ; Montefiori, David ; Klotman, Mary E. ; Sanders, Rogier W. ; Shattock, Robin J. ; Negri, Donatella ; Cara, Andrea. / Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers. In: npj Vaccines. 2022 ; Vol. 7, No. 1.

BibTeX

@article{ddfadc9c4fb844c8bcec0bb3bc97e10e,
title = "Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers",
abstract = "Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV-1 immunogen design demonstrated that native-like HIV-1 Envelope (Env) trimers that mimic the structure of virion-associated Env induce neutralization breadth in rabbits and macaques. Here, we describe the development of an IDLV-based HIV-1 vaccine expressing either soluble ConSOSL.UFO.664 or membrane-tethered ConSOSL.UFO.750 native-like Env immunogens with enhanced bNAb epitopes exposure. We show that IDLV can be pseudotyped with properly folded membrane-tethered native-like UFO.750 trimers. After a single IDLV injection in BALB/c mice, IDLV-UFO.750 induced a faster humoral kinetic as well as higher levels of anti-Env IgG compared to IDLV-UFO.664. IDLV-UFO.750 vaccinated cynomolgus macaques developed unusually long-lasting anti-Env IgG antibodies, as underlined by their remarkable half-life both after priming and boost with IDLV. After boosting with recombinant ConM SOSIP.v7 protein, two animals developed neutralization activity against the autologous tier 1B ConS virus mediated by V1/V2 and V3 glycan sites responses. By combining the possibility to display stabilized trimeric Env on the vector particles with the ability to induce sustained humoral responses, IDLVs represent an appropriate strategy for delivering rationally designed antigens to progress towards an effective HIV-1 vaccine.",
author = "Alessandra Gallinaro and Pirillo, {Maria Franca} and Yoann Aldon and Serena Cecchetti and Zuleika Michelini and Antonella Tinari and Martina Borghi and Andrea Canitano and McKay, {Paul F.} and Roberta Bona and Vescio, {Maria Fenicia} and Felicia Grasso and Maria Blasi and Silvia Baroncelli and Gabriella Scarlatti and Celia LaBranche and David Montefiori and Klotman, {Mary E.} and Sanders, {Rogier W.} and Shattock, {Robin J.} and Donatella Negri and Andrea Cara",
note = "Funding Information: We are grateful to Dr. Omar Leoni and Dr. Gianluca Panzini for veterinary assistance and to all personnel responsible for the animal facility: Antonio Di Virgilio, Luigia Cancemi, Maurizio Chiodi, Anna Rita Lamagna, Isabella Marcucci, and Francesca Ubaldi. We are grateful to Stefania Donnini for secretarial assistance; Ferdinando Costa and Patrizia Cocco for technical support. We also thank Iole Farina for her help in NHP samples processing. We thank Dr. Dietmar Katinger for providing recombinant human monoclonal antibody to HIV-1 gp120, 2G12 (#AB002); recombinant human monoclonal antibody to HIV-1 gp120, PT145; ConM SOSIP.v7 and ConSOSL.UFO.664 Protein and MPLA adjuvant. We thank Marit J. van Gils and Emma I. M. M. Reiss for donating recombinant human monoclonal antibody to HIV-1 gp120, PGDM1400. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (NIAID; 1P01AI110485-01A1 to M.E.K.) and Italian Ministry of Health Ricerca Finalizzata (PE-2011-02347035 to A. Cara and PE-2016-02364927). This project has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under grant agreement no. 681137 (EAVI2020) and the European Union{\textquoteright}s Seventh Programme for Research, Technological Development and Demonstration under grant agreement no. 280873 (ADITEC; to A. Cara and D.N.). We thank Fondation Dormeur, Vaduz for the donation of laboratory instruments relevant to this project to the Istituto Superiore di Sanit{\`a}. The following reagents were obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID, NIH: Polyclonal Anti-Human Immunodeficiency Virus Type 1 SF2 p24 (antiserum, Rabbit), ARP-4250, contributed by DAIDS/NIAID; produced by BioMelecular Technologies; SIVmac239 p27 Recombinant Protein from NIAID, DAIDS (cat# 13446). The article was previously published as a preprint: Gallinaro, A. et al. Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane-tethered Native-Like HIV-1 Envelope Trimers. bioRxiv 2021.10.08.462761; https://doi.org/10.1101/2021.10.08.462761 Funding Information: We are grateful to Dr. Omar Leoni and Dr. Gianluca Panzini for veterinary assistance and to all personnel responsible for the animal facility: Antonio Di Virgilio, Luigia Cancemi, Maurizio Chiodi, Anna Rita Lamagna, Isabella Marcucci, and Francesca Ubaldi. We are grateful to Stefania Donnini for secretarial assistance; Ferdinando Costa and Patrizia Cocco for technical support. We also thank Iole Farina for her help in NHP samples processing. We thank Dr. Dietmar Katinger for providing recombinant human monoclonal antibody to HIV-1 gp120, 2G12 (#AB002); recombinant human monoclonal antibody to HIV-1 gp120, PT145; ConM SOSIP.v7 and ConSOSL.UFO.664 Protein and MPLA adjuvant. We thank Marit J. van Gils and Emma I. M. M. Reiss for donating recombinant human monoclonal antibody to HIV-1 gp120, PGDM1400. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (NIAID; 1P01AI110485-01A1 to M.E.K.) and Italian Ministry of Health Ricerca Finalizzata (PE-2011-02347035 to A. Cara and PE-2016-02364927). This project has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement no. 681137 (EAVI2020) and the European Union?s Seventh Programme for Research, Technological Development and Demonstration under grant agreement no. 280873 (ADITEC; to A. Cara and D.N.). We thank Fondation Dormeur, Vaduz for the donation of laboratory instruments relevant to this project to the Istituto Superiore di Sanit?. The following reagents were obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID, NIH: Polyclonal Anti-Human Immunodeficiency Virus Type 1 SF2 p24 (antiserum, Rabbit), ARP-4250, contributed by DAIDS/NIAID; produced by BioMelecular Technologies; SIVmac239 p27 Recombinant Protein from NIAID, DAIDS (cat# 13446). The article was previously published as a preprint: Gallinaro, A. et al. Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane-tethered Native-Like HIV-1 Envelope Trimers. bioRxiv 2021.10.08.462761; https://doi.org/10.1101/2021.10.08.462761 Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
day = "1",
doi = "10.1038/s41541-022-00465-1",
language = "English",
volume = "7",
journal = "npj Vaccines",
issn = "2059-0105",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers

AU - Gallinaro, Alessandra

AU - Pirillo, Maria Franca

AU - Aldon, Yoann

AU - Cecchetti, Serena

AU - Michelini, Zuleika

AU - Tinari, Antonella

AU - Borghi, Martina

AU - Canitano, Andrea

AU - McKay, Paul F.

AU - Bona, Roberta

AU - Vescio, Maria Fenicia

AU - Grasso, Felicia

AU - Blasi, Maria

AU - Baroncelli, Silvia

AU - Scarlatti, Gabriella

AU - LaBranche, Celia

AU - Montefiori, David

AU - Klotman, Mary E.

AU - Sanders, Rogier W.

AU - Shattock, Robin J.

AU - Negri, Donatella

AU - Cara, Andrea

N1 - Funding Information: We are grateful to Dr. Omar Leoni and Dr. Gianluca Panzini for veterinary assistance and to all personnel responsible for the animal facility: Antonio Di Virgilio, Luigia Cancemi, Maurizio Chiodi, Anna Rita Lamagna, Isabella Marcucci, and Francesca Ubaldi. We are grateful to Stefania Donnini for secretarial assistance; Ferdinando Costa and Patrizia Cocco for technical support. We also thank Iole Farina for her help in NHP samples processing. We thank Dr. Dietmar Katinger for providing recombinant human monoclonal antibody to HIV-1 gp120, 2G12 (#AB002); recombinant human monoclonal antibody to HIV-1 gp120, PT145; ConM SOSIP.v7 and ConSOSL.UFO.664 Protein and MPLA adjuvant. We thank Marit J. van Gils and Emma I. M. M. Reiss for donating recombinant human monoclonal antibody to HIV-1 gp120, PGDM1400. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (NIAID; 1P01AI110485-01A1 to M.E.K.) and Italian Ministry of Health Ricerca Finalizzata (PE-2011-02347035 to A. Cara and PE-2016-02364927). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 681137 (EAVI2020) and the European Union’s Seventh Programme for Research, Technological Development and Demonstration under grant agreement no. 280873 (ADITEC; to A. Cara and D.N.). We thank Fondation Dormeur, Vaduz for the donation of laboratory instruments relevant to this project to the Istituto Superiore di Sanità. The following reagents were obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID, NIH: Polyclonal Anti-Human Immunodeficiency Virus Type 1 SF2 p24 (antiserum, Rabbit), ARP-4250, contributed by DAIDS/NIAID; produced by BioMelecular Technologies; SIVmac239 p27 Recombinant Protein from NIAID, DAIDS (cat# 13446). The article was previously published as a preprint: Gallinaro, A. et al. Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane-tethered Native-Like HIV-1 Envelope Trimers. bioRxiv 2021.10.08.462761; https://doi.org/10.1101/2021.10.08.462761 Funding Information: We are grateful to Dr. Omar Leoni and Dr. Gianluca Panzini for veterinary assistance and to all personnel responsible for the animal facility: Antonio Di Virgilio, Luigia Cancemi, Maurizio Chiodi, Anna Rita Lamagna, Isabella Marcucci, and Francesca Ubaldi. We are grateful to Stefania Donnini for secretarial assistance; Ferdinando Costa and Patrizia Cocco for technical support. We also thank Iole Farina for her help in NHP samples processing. We thank Dr. Dietmar Katinger for providing recombinant human monoclonal antibody to HIV-1 gp120, 2G12 (#AB002); recombinant human monoclonal antibody to HIV-1 gp120, PT145; ConM SOSIP.v7 and ConSOSL.UFO.664 Protein and MPLA adjuvant. We thank Marit J. van Gils and Emma I. M. M. Reiss for donating recombinant human monoclonal antibody to HIV-1 gp120, PGDM1400. This work was supported in part by grants from the National Institute of Allergy and Infectious Diseases (NIAID; 1P01AI110485-01A1 to M.E.K.) and Italian Ministry of Health Ricerca Finalizzata (PE-2011-02347035 to A. Cara and PE-2016-02364927). This project has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement no. 681137 (EAVI2020) and the European Union?s Seventh Programme for Research, Technological Development and Demonstration under grant agreement no. 280873 (ADITEC; to A. Cara and D.N.). We thank Fondation Dormeur, Vaduz for the donation of laboratory instruments relevant to this project to the Istituto Superiore di Sanit?. The following reagents were obtained through the NIH HIV Reagent Program, Division of AIDS, NIAID, NIH: Polyclonal Anti-Human Immunodeficiency Virus Type 1 SF2 p24 (antiserum, Rabbit), ARP-4250, contributed by DAIDS/NIAID; produced by BioMelecular Technologies; SIVmac239 p27 Recombinant Protein from NIAID, DAIDS (cat# 13446). The article was previously published as a preprint: Gallinaro, A. et al. Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane-tethered Native-Like HIV-1 Envelope Trimers. bioRxiv 2021.10.08.462761; https://doi.org/10.1101/2021.10.08.462761 Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV-1 immunogen design demonstrated that native-like HIV-1 Envelope (Env) trimers that mimic the structure of virion-associated Env induce neutralization breadth in rabbits and macaques. Here, we describe the development of an IDLV-based HIV-1 vaccine expressing either soluble ConSOSL.UFO.664 or membrane-tethered ConSOSL.UFO.750 native-like Env immunogens with enhanced bNAb epitopes exposure. We show that IDLV can be pseudotyped with properly folded membrane-tethered native-like UFO.750 trimers. After a single IDLV injection in BALB/c mice, IDLV-UFO.750 induced a faster humoral kinetic as well as higher levels of anti-Env IgG compared to IDLV-UFO.664. IDLV-UFO.750 vaccinated cynomolgus macaques developed unusually long-lasting anti-Env IgG antibodies, as underlined by their remarkable half-life both after priming and boost with IDLV. After boosting with recombinant ConM SOSIP.v7 protein, two animals developed neutralization activity against the autologous tier 1B ConS virus mediated by V1/V2 and V3 glycan sites responses. By combining the possibility to display stabilized trimeric Env on the vector particles with the ability to induce sustained humoral responses, IDLVs represent an appropriate strategy for delivering rationally designed antigens to progress towards an effective HIV-1 vaccine.

AB - Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV-1 immunogen design demonstrated that native-like HIV-1 Envelope (Env) trimers that mimic the structure of virion-associated Env induce neutralization breadth in rabbits and macaques. Here, we describe the development of an IDLV-based HIV-1 vaccine expressing either soluble ConSOSL.UFO.664 or membrane-tethered ConSOSL.UFO.750 native-like Env immunogens with enhanced bNAb epitopes exposure. We show that IDLV can be pseudotyped with properly folded membrane-tethered native-like UFO.750 trimers. After a single IDLV injection in BALB/c mice, IDLV-UFO.750 induced a faster humoral kinetic as well as higher levels of anti-Env IgG compared to IDLV-UFO.664. IDLV-UFO.750 vaccinated cynomolgus macaques developed unusually long-lasting anti-Env IgG antibodies, as underlined by their remarkable half-life both after priming and boost with IDLV. After boosting with recombinant ConM SOSIP.v7 protein, two animals developed neutralization activity against the autologous tier 1B ConS virus mediated by V1/V2 and V3 glycan sites responses. By combining the possibility to display stabilized trimeric Env on the vector particles with the ability to induce sustained humoral responses, IDLVs represent an appropriate strategy for delivering rationally designed antigens to progress towards an effective HIV-1 vaccine.

UR - http://www.scopus.com/inward/record.url?scp=85128623382&partnerID=8YFLogxK

U2 - 10.1038/s41541-022-00465-1

DO - 10.1038/s41541-022-00465-1

M3 - Article

C2 - 35449174

VL - 7

JO - npj Vaccines

JF - npj Vaccines

SN - 2059-0105

IS - 1

M1 - 44

ER -

ID: 23349928