ABSTRACT
A case of human immunodefi ciency virus (HIV) infection from North India is described with a 20-year follow-up. Patient fi rst reported in 1993 when he was detected HIV positive, remained healthy without treatment, married in 1999 and did not transmit the disease to his children or his wife and was lost to follow-up. He was thought to be an elite controller. After 15 years of the initial visit, his CD4 cells, however, were found to be low, with a viral load of 10,000/copies/ml. He was negative for human leukocyte antigen B57 and B27 alleles with a normal expression of CCR5 and CXCR4 on CD4 cells. Lymphocytes showed a signifi cant production of tumour necrosis factor alpha and interferon , but not of interleukin (IL)-2, IL4 or IL10. It is possible that gut infection, common in India, could have triggered T cell activation in the ensuing years, resulting in activation of HIV. The case illustrates the signifi cance of long-term follow-up of these patients for timely institution of anti-retroviral therapy.
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.