Abstract

The present studies examine the breadth and magnitude of neutralizing antibody responses in small animals and rhesus monkeys after various immunization regimens. Using a standardized multi-tier panel of reference Env pseudoviruses for neutralizing antibody assessment, we show that both protein immunization, and DNA prime, rAd boost immunization, can generate high antibody titers. Ongoing studies are evaluating novel immunogens based on structure-based information from studies of the HIV-1 envelope glycoprotein. The use of novel transgenic mouse models allows testing of immunogen strategies based on our previous studies of HIV neutralizing antibody structure and function.

  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 #
1ZIAAI005012-16
Application #
9564619
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2017
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
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
Bricault, Christine A; Kovacs, James M; Badamchi-Zadeh, Alexander et al. (2018) Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs. J Virol :
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
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
Chuang, Gwo-Yu; Geng, Hui; Pancera, Marie et al. (2017) Structure-Based Design of a Soluble Prefusion-Closed HIV-1 Env Trimer with Reduced CD4 Affinity and Improved Immunogenicity. J Virol 91:
Cheng, Cheng; Pancera, Marie; Bossert, Adam et al. (2016) Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody. J Virol 90:2740-55
Tian, Ming; Cheng, Cheng; Chen, Xuejun et al. (2016) Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell 166:1471-1484.e18
Ingale, Jidnyasa; Tran, Karen; Kong, Leopold et al. (2014) Hyperglycosylated stable core immunogens designed to present the CD4 binding site are preferentially recognized by broadly neutralizing antibodies. J Virol 88:14002-16
Pegu, Amarendra; Yang, Zhi-yong; Boyington, Jeffrey C et al. (2014) Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci Transl Med 6:243ra88
Chakrabarti, Bimal K; Feng, Yu; Sharma, Shailendra Kumar et al. (2013) Robust neutralizing antibodies elicited by HIV-1 JRFL envelope glycoprotein trimers in nonhuman primates. J Virol 87:13239-51

Showing the most recent 10 out of 30 publications