Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus-like particles.
Journal Article (Journal Article)
The broadly neutralizing antibody against HIV-1, b12, binds to the CD4 binding site (CD4bs) on the outer domain (OD) of the gp120 subunit of HIV-1 Env. We have previously reported the design of an E. coli expressed fragment of HIV-1 gp120, b122a, containing about 70% of the b12 epitope with the idea of focusing the immune response to this structure. Since the b122a structure was found to be only partially folded, as assessed by circular dichroism and protease resistance, we attempted to stabilize it by the introduction of additional disulfide bonds. One such mutant, b122a1-b showed increased stability and bound b12 with 30-fold greater affinity as compared to b122a. Various b122a and OD fragment proteins were displayed on the surface of Qβ virus-like particles. Sera raised against these particles in six-month long rabbit immunization studies could neutralize Tier1 viruses across different subtypes with the best results observed with b122a1-b displayed particles. Significantly higher amounts of antibodies directed towards the CD4bs were also elicited by particles displaying b122a1-b. This study highlights the ability of fragment immunogens to focus the antibody response to the conserved CD4bs of HIV-1.
Full Text
Duke Authors
Cited Authors
- Purwar, M; Pokorski, JK; Singh, P; Bhattacharyya, S; Arendt, H; DeStefano, J; La Branche, CC; Montefiori, DC; Finn, MG; Varadarajan, R
Published Date
- October 8, 2018
Published In
Volume / Issue
- 36 / 42
Start / End Page
- 6345 - 6353
PubMed ID
- 30220462
Pubmed Central ID
- PMC6364316
Electronic International Standard Serial Number (EISSN)
- 1873-2518
Digital Object Identifier (DOI)
- 10.1016/j.vaccine.2018.07.032
Language
- eng
Conference Location
- Netherlands