Neutralizing antibody patterns and viral escape in HIV-1 non-B subtype chronically infected treatment-naive individuals

Issue title: Humoral immune response against HIV-1

Guest editors: M.K. Gorny

Article type: Research Article

Authors: Kelly, Halonna R.^a | Urbanski, Mateusz^a | Burda, Sherri^a | Zhong, Ping^{a; c} | Konings, Frank^b | Nanfack, Joseph^d | Tongo, Marcel^d | Kinge, Thompson^e | Achkar, Jacqueline^c | Nyambi, Phillipe^{a; f; *}

Affiliations: [a] Department of Pathology, New York University School of Medicine, New York, NY, USA | [b] Department of Microbiology, New York University School of Medicine, New York, NY, USA | [c] Shanghai Center for Disease Control and Prevention, P.R. China | [d] Laboratoire de Sante Hygiene Mobile, Yaoundé, Cameroon | [e] Ministry of Health, Yaoundé, Cameroon | [f] Research Enhancement Award Program, Veterans Affairs New York Harbor Healthcare Systems, New York, NY, USA | New York University School of Medicine, c/o Veterans Affairs Medical Center, 423 East, 23rd Street, Room 18124N New York, NY 10010, USA

Correspondence: [*] Corresponding author: Phillipe Nyambi, Department of Pathology, New York University School of Medicine, c/o V.A. Medical Center, 423 E 23rd Street, Room 18124N, New York, NY 10010, USA. Tel.: +1 212 263 6769; Fax: +1 212 951 6321; E-mail: phillipe.nyambi@med.nyu.edu.

Abstract: Here we studied the patterns of generation of neutralizing antibodies (NAbs) and virus escape during non-B subtype HIV-1 chronic infection among asymptomatic patients, and established whether a correlation exists between the generation of NAbs and the kinetics of CD4 T-cell decline. Therefore, sequential viruses and plasma obtained at 6 months to one year intervals over a three years period from ten HIV-1 group M subtype A, CRF02_AG, G, and H infected treatment-naïve individuals were tested in neutralization assays. Overall, NAbs were present in all ten individuals, and had the capacity to neutralize autologous virus obtained six months earlier. Eight of the ten subjects showed an increasing capacity to neutralize early viruses and a low capacity to neutralize contemporaneous and later time-point viruses. The neutralizing activities within these individuals resulted in emergence of neutralization resistant viruses, and with the subsequent generation of more NAbs to the emerging resistant viruses. In the remaining two individuals, the capacity to neutralize early, contemporaneous, and later time-point viruses remained conserved. While the kinetics of CD4 T-cell decline varied among all ten individuals, there was no correlation with the capacity to generate NAbs in that, sequential plasmas from individuals with moderately or rapidly declining CD4 T-cells were capable of neutralizing early sequential viruses. We conclude from this study that in non-B subtype chronically infected asymptomatic patients with moderately and rapidly declining CD4 T-cells, potent NAbs are readily generated as the virus evolves to escape the effect of these antibodies.

Keywords: Neutralizing antibodies, non-B HIV-1, chronic infection, CD4 T-cell decline

DOI: 10.3233/HAB-2005-143-406

Journal: Human Antibodies, vol. 14, no. 3-4, pp. 89-99, 2005