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Mimotopes selected by biopanning with high-titer HIV-neutralizing antibodies in plasma from Chinese slow progressors
Zhang, Xiaoli; Han, Xiaoxu; Dai, Di; Mingjia, Bao; Zhang, Zining; Zhang, Min; Bice, Tristan; Zhao, Min; Cao, Yaming; Shang, Hong.
  • Zhang, Xiaoli; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Han, Xiaoxu; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Dai, Di; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Mingjia, Bao; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Zhang, Zining; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Zhang, Min; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Bice, Tristan; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Zhao, Min; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Cao, Yaming; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
  • Shang, Hong; China Medical University. The First Affiliated Hospital. Key Laboratory of Immunology of AIDS. Liaoning. CN
Braz. j. infect. dis ; 16(6): 510-516, Nov.-Dec. 2012. ilus, tab
Article in English | LILACS | ID: lil-658919
ABSTRACT

OBJECTIVE:

One approach to identifying HIV-1 vaccine candidates is to dissect the natural antiviral immune response in treatment-naïve individuals infected for over ten years, considered slow progressor patients (SPs). It is suspected that SP plasma has strongly neutralizing antibodies (NAb) targeting specific HIV viral epitopes.

METHODS:

NAbs levels of 11 HIV-1-infected SPs were detected by PBMC-based neutralization assays. To investigate SP NAb epitope, this study used a biopanning approach to obtain mimotopes of HIV-1 that were recognized by SP plasma NAbs. IgG was purified from hightiter NAb SP plasma, and used as the ligand for three rounds of biopanning to select HIV-specific mimotopes from a phage-displayed random peptide library. Double-antibody sandwich ELISA, competitive inhibition assays, and peptide sequence analysis were used to evaluate the characteristics of phage-borne mimotopes.

RESULTS:

SPs had significantly more plasma neutralizing activity than typical progressors (TPs) (p = 0.04). P2 and P9 plasma, which have highest-titer HIV-NAb, were selected as ligands for biopanning. After three rounds of biopanning, 48 phage clones were obtained, of which 22 clones were consistent with requirement, binding with HIV-1 positive plasma and unbinding with HIV-1 negative plasma. Compared with linear HIV-1 protein sequence and HIV-1 protein structure files, only 12 clones were possible linear mimotopes of NAbs. In addition, the C40 clone located in gp41 CHR was found to be a neutralizing epitope, which could inhibit pooled HIV-1 positive plasma reaction.

CONCLUSION:

Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.
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Full text: Available Index: LILACS (Americas) Main subject: HIV Antibodies / HIV Infections / HIV-1 / Antibodies, Neutralizing / Epitopes Type of study: Prognostic study Limits: Humans Country/Region as subject: Asia Language: English Journal: Braz. j. infect. dis Journal subject: Communicable Diseases Year: 2012 Type: Article / Project document Affiliation country: China Institution/Affiliation country: China Medical University/CN

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Full text: Available Index: LILACS (Americas) Main subject: HIV Antibodies / HIV Infections / HIV-1 / Antibodies, Neutralizing / Epitopes Type of study: Prognostic study Limits: Humans Country/Region as subject: Asia Language: English Journal: Braz. j. infect. dis Journal subject: Communicable Diseases Year: 2012 Type: Article / Project document Affiliation country: China Institution/Affiliation country: China Medical University/CN