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Research Article
A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
Jean-Francois Bruxelle
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
Corresponding Author
Ralph Pantophlet
Faculty of Health Sciences, Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada
Corresponding Author
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation evoked antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, likely explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.
Keywords
Antibody, Oligomannose, Glycoconjugate, Adjuvant, HIV
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Research Article
A glycoside analog of mammalian oligomannose formulated with a TLR4-stimulating adjuvant elicits HIV-1 cross-reactive antibodies
Jean-Francois Bruxelle
Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
Corresponding Author
Ralph Pantophlet
Faculty of Health Sciences, Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 06 Jan, 2021
No community comments so far
No comments provided
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved the use of non-human vertebrates.
- The author has confirmed that all appropriate ethical guidelines for the handling and use of animals in research have been followed and details of the oversight board have been included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
The occurrence of oligomannose-specific broadly neutralizing antibodies (bnAbs) has spurred efforts to develop immunogens that can elicit similar antibodies. Here, we report on the antigenicity and immunogenicity of a CRM197-conjugate of a previously reported oligomannose mimetic. Oligomannose-specific bnAbs that are less dependent on interactions with the HIV envelope protein sequence showed strong binding to the glycoconjugates, with affinities approximating those reported for their cognate epitope. The glycoconjugate is also recognized by germline precursors of oligomannose-specific bnAbs, albeit with the expected low avidity, supporting its potential as an immunogen. Immunization of human-antibody transgenic mice revealed that only a TLR4-stimulating adjuvant formulation evoked antibodies able to bind a panel of recombinant HIV trimers. These antibodies bound at relatively modest levels, likely explaining their inability to neutralize HIV infectivity. Nevertheless, these findings contribute further to understanding conditions for eliciting HIV-cross-reactive oligomannose-specific antibodies and inform on next steps for improving on the elicited response.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5