Publication Date:
2013-03-30
Description:
Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689846/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689846/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph -- Julien, Jean-Philippe -- Menis, Sergey -- Ota, Takayuki -- Kalyuzhniy, Oleksandr -- McGuire, Andrew -- Sok, Devin -- Huang, Po-Ssu -- MacPherson, Skye -- Jones, Meaghan -- Nieusma, Travis -- Mathison, John -- Baker, David -- Ward, Andrew B -- Burton, Dennis R -- Stamatatos, Leonidas -- Nemazee, David -- Wilson, Ian A -- Schief, William R -- 5T32AI007606-10/AI/NIAID NIH HHS/ -- AI081625/AI/NIAID NIH HHS/ -- AI33292/AI/NIAID NIH HHS/ -- AI84817/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P30 AI027767-24/AI/NIAID NIH HHS/ -- P41RR001209/RR/NCRR NIH HHS/ -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI073148/AI/NIAID NIH HHS/ -- R01 AI081625/AI/NIAID NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- R37 AI033292/AI/NIAID NIH HHS/ -- T32 CA080416/CA/NCI NIH HHS/ -- T32CA080416/CA/NCI NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Y1-CO-1020/CO/NCI NIH HHS/ -- Y1-GM-1104/GM/NIGMS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2013 May 10;340(6133):711-6. doi: 10.1126/science.1234150. Epub 2013 Mar 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23539181" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/chemistry/genetics/*immunology
;
Amino Acid Sequence
;
Animals
;
Antibodies, Neutralizing/immunology
;
Antigens, CD4/immunology
;
B-Lymphocytes/immunology
;
Crystallography, X-Ray
;
DNA Mutational Analysis
;
Germ Cells/*immunology
;
HIV Envelope Protein gp120/chemistry/genetics/*immunology
;
HIV Infections/*prevention & control
;
HIV-1/*immunology
;
Humans
;
Macaca
;
Mice
;
Models, Animal
;
Molecular Sequence Data
;
Nanoparticles
;
Protein Engineering
;
Protein Structure, Tertiary
;
Receptors, Antigen, B-Cell/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
