Abstract

Based on our understanding of envelope-based mechanisms of humoral evasion, we have attempted to design envelope-based immunogens with these mechanisms disabled. Such modied immunogens with weakened defenses may elicit more broadly neutralizing antibodies. We have also devised scaffolding technologies, as a means of presenting structural mimics of the epitopes of broadly neutralizing antibodies to assist in their re-elicitation. Scaffolds can be non-homologous proteins, identified through searches of the entire protein data bank. Alternatively, scaffolds can be homologous proteins, which are structurally similar, but antigenically distinct from the HIV-1 envelope glycoproteins. An alternative to scaffolding involves """"""""cloaking"""""""", where the surface of a molecule, not involved in eliciting a desired response, is altered between """"""""prime"""""""" and """"""""boost"""""""" phases of immunization.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI005024-08
Application #
7964827
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2009
Total Cost
$169,604
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Xu, Kai; Acharya, Priyamvada; Kong, Rui et al. (2018) Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat Med 24:857-867
Rawi, Reda; Mall, Raghvendra; Kunji, Khalid et al. (2018) PaRSnIP: sequence-based protein solubility prediction using gradient boosting machine. Bioinformatics 34:1092-1098
Rutten, Lucy; Lai, Yen-Ting; Blokland, Sven et al. (2018) A Universal Approach to Optimize the Folding and Stability of Prefusion-Closed HIV-1 Envelope Trimers. Cell Rep 23:584-595
Zhang, Peng; Gorman, Jason; Geng, Hui et al. (2018) Interdomain Stabilization Impairs CD4 Binding and Improves Immunogenicity of the HIV-1 Envelope Trimer. Cell Host Microbe 23:832-844.e6
Georgiev, Ivelin S; Joyce, Michael Gordon; Chen, Rita E et al. (2018) Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens. ACS Infect Dis 4:788-796
Kwong, Peter D; Mascola, John R (2018) HIV-1 Vaccines Based on Antibody Identification, B Cell Ontogeny, and Epitope Structure. Immunity 48:855-871
Duan, Hongying; Chen, Xuejun; Boyington, Jeffrey C et al. (2018) Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies. Immunity 49:301-311.e5
Alam, S Munir; Aussedat, Baptiste; Vohra, Yusuf et al. (2017) Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide. Sci Transl Med 9:
Sastry, Mallika; Zhang, Baoshan; Chen, Man et al. (2017) Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus. PLoS One 12:e0186854
Joyce, M Gordon; Georgiev, Ivelin S; Yang, Yongping et al. (2017) Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains. Cell Rep 21:2992-3002

Showing the most recent 10 out of 58 publications