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Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs

View ORCID ProfileBlasi Maria, Negri Donatella, Saunders O Kevin, Baker J Erich, Stadtler Hannah, LaBranche Celia, Mildenberg Benjamin, Morton Georgeanna, Ciarla Andrew, Shen Xiaoying, Wang Yunfei, Rountree Wes, Balakumaran Bala, Santra Sampa, Haynes F Barton, Moody M Anthony, Cara Andrea, Klotman E Mary
doi: https://doi.org/10.1101/2020.03.06.980680
Blasi Maria
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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  • ORCID record for Blasi Maria
  • For correspondence: maria.blasi@duke.edu mary.klotman@dm.duke.edu
Negri Donatella
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
3Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
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Saunders O Kevin
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Baker J Erich
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Stadtler Hannah
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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LaBranche Celia
4Department of Surgery, Duke University School of Medicine, Durham, NC, USA
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Mildenberg Benjamin
5Beth Israel Deaconess Medical Center, Boston, MA, USA
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Morton Georgeanna
5Beth Israel Deaconess Medical Center, Boston, MA, USA
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Ciarla Andrew
5Beth Israel Deaconess Medical Center, Boston, MA, USA
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Shen Xiaoying
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Wang Yunfei
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Rountree Wes
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Balakumaran Bala
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Santra Sampa
5Beth Israel Deaconess Medical Center, Boston, MA, USA
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Haynes F Barton
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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Moody M Anthony
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
6Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA
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Cara Andrea
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
7National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy
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Klotman E Mary
1Department of Medicine, Duke University School of Medicine, Durham, NC, USA
2Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA
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  • For correspondence: maria.blasi@duke.edu mary.klotman@dm.duke.edu
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Abstract

A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study we report the immunogenicity, safety and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Env induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six month after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Our results show that while IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms, the use of non-stabilized sequential envelope trimers did not induce broadly neutralizing antibody responses.

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Posted March 08, 2020.
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Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs
Blasi Maria, Negri Donatella, Saunders O Kevin, Baker J Erich, Stadtler Hannah, LaBranche Celia, Mildenberg Benjamin, Morton Georgeanna, Ciarla Andrew, Shen Xiaoying, Wang Yunfei, Rountree Wes, Balakumaran Bala, Santra Sampa, Haynes F Barton, Moody M Anthony, Cara Andrea, Klotman E Mary
bioRxiv 2020.03.06.980680; doi: https://doi.org/10.1101/2020.03.06.980680
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Immunogenicity, safety and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs
Blasi Maria, Negri Donatella, Saunders O Kevin, Baker J Erich, Stadtler Hannah, LaBranche Celia, Mildenberg Benjamin, Morton Georgeanna, Ciarla Andrew, Shen Xiaoying, Wang Yunfei, Rountree Wes, Balakumaran Bala, Santra Sampa, Haynes F Barton, Moody M Anthony, Cara Andrea, Klotman E Mary
bioRxiv 2020.03.06.980680; doi: https://doi.org/10.1101/2020.03.06.980680

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