Rational HIV Immunogen Design to Target Specific Germline B Cell Receptors
Open accessAbstract
Building Better Vaccines: In the past few years, several highly potent, broadly neutralizing antibodies (bNAbs) specific for the gp120 envelope protein of HIV-1 have been discovered. The goal of this work is to use this information to inform the design of vaccines that are able to induce such antibodies (see the Perspective by Crowe ). However, because of extensive somatic hypermutation, the epitope bound by these antibodies often does not bind to the germline sequence. Jardine et al. (p. 711 , published online 28 March; see the cover) used computational analysis and in vitro screening to design an immunogen that could bind to VRC01-class bNAbs and to their germline precursors. Georgiev et al. (p. 751 ) took advantage of the fact that only four sites on the HIV viral envelope protein seem to bind bNAbs, and sera that contain particular bNAbs show characteristic patterns of neutralization. An algorithm was developed that could successfully delineate the neutralization specificity of antibodies present in polyclonal sera from HIV-infected patients.
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Structure-based design of epitopes recognized by template neutralizing antibodies can engineer antigenicity.
“We and others have engineered antigenicity (13-17) through structure-based design of the epitopes recognized by template neutralizing antibodies.”
From Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus (2013) · cites this paper as [16]
Atomic-level control of antigenicity increasingly appears to be within the reach of structure-based design.
“Importantly, atomic-level control of antigenicity increasingly appears to be within the reach of structure-based design (16, 39, 40).”
From Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus (2013) · cites this paper as [16]
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- Authors
- Jardine, J., Julien, J.-P., Menis, S., Ota, T., Kalyuzhniy, O., McGuire, A., Sok, D., Huang, P.-S., MacPherson, S., Jones, M., Nieusma, T., Mathison, J., Baker, D., Ward, A. B., Burton, D. R., Stamatatos, L., Nemazee, D., Wilson, I. A., & Schief, W. R.
- Affiliations
- Scripps Research Institute (US)
- Center for Infectious Disease Research (US)
- University of Washington (US)
- Corresponding author
- Jardine, Joseph
- Julien, Jean-Philippe
- Menis, Sergey
- Schief, William R.
- ORCID
- Venue
- Science
- Published
- 2013-05-10
- Volume
- 340
- Issue
- 6133
- Pages
- 711-716
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3689846
- OpenAlex
- W2052937459
- Cited by
- 770
- References
- 48
- Citations by year
- 2026: 43 · 2025: 47 · 2024: 56 · 2023: 56 · 2022: 63 · 2021: 59 · 2020: 55 · 2019: 49 · 2018: 58 · 2017: 74 · 2016: 55 · 2015: 63 · 2014: 62 · 2013: 30
- FWCI
- 32.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Cancer Institute (Y1-CO-1020, T32CA080416)
- National Institute of General Medical Sciences (Y1-GM-1104)
- National Institute of Allergy and Infectious Diseases (T32AI007606, AI-33292, AI081625, R37AI033292, R56AI084817, R01AI033292, R01AI073148, R01AI084817, R01AI081625, AI84817, UM1AI100663, P01AI094419, P30AI027767)
- National Center for Research Resources (P41RR001209)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- HIV-1 vaccine, broadly neutralizing antibodies, immunogen design, CD4 binding site, B cell activation
- MeSH terms
- Amino Acid Sequence, Animals, B-Lymphocytes, DNA Mutational Analysis, Germ Cells, Humans, Macaca, Molecular Sequence Data, Receptors, Antigen, B-Cell, Protein Engineering, HIV-1, HIV Infections, HIV Envelope Protein gp120, CD4 Antigens, AIDS Vaccines, Protein Structure, Tertiary, Crystallography, X-Ray, Models, Animal, Mice, Nanoparticles, Antibodies, Neutralizing
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