Expansion of antibody secreting cells and modulation of neutralizing antibody activity in HIV infected individuals undergoing structured treatment interruptions.

Abstract

BACKGROUND:

HIV-1 infection generates numerous abnormalities in the B cell compartment which can be partly reversed by antiretroviral therapy. Our aim was to evaluate the effects that re-exposure to HIV antigens might have on the frequency and functionality of antibody secreting cells (ASC) in patients undergoing structured treatment interruptions (STI). As re-exposure to viral antigens may also boost the production of (neutralizing) antibodies, we also assessed the neutralizing activities during STI cycles.

METHODS:

Retrospective study of 10 patients undergoing 3 cycles of STI with 2 weeks on and 4 weeks off HAART. ASC frequencies were determined by flow cytometry in samples obtained at the beginning and the end of STI. Neutralization capacity, total IgG concentration and anti-gp120-IgG titres were evaluated.

RESULTS:

As expected, median viral loads were higher at the end of STI compared to on-HAART time points. The level of CD27 and CD38 expressing ACS followed the same pattern; with ASC being elevated up to 16 fold in some patients (median increase of 3.5% ± 4.13). Eight out of 10 patients maintained stable total IgG levels during the study. After purifying IgG fractions from plasma, HIV-neutralizing activity was observed in the two subjects with highest anti-gp120 titers. In one of these patients the neutralizing activity remained constant while the other showed elevated neutralizing Ab after first STI and once treatment was reinitiated after the 2nd STI.

CONCLUSIONS:

Our data suggest that STI and its associated transient increases in viral load drive the frequencies of ASC in an antigen-specific manner. In some subjects, this re-exposure to autologous virus boosts the presence of neutralizing antibodies, similar to what is seen after influenza vaccination. STI may not boost clinically beneficial nAb levels but offers opportunities to isolate nAb producing cells at considerably higher levels than in subjects with completely suppressed viral replication.

• Authors: Anuska Llano, Jorge Carrillo, Beatriz Mothe, Lidia Ruiz, Silvia Marfil, Elisabet García, Eloísa Yuste, Víctor Sánchez, Bonaventura Clotet, Julià Blanco, Christian Brander
• Journal: Journal of translational medicine (J Transl Med) Vol. 11 Pg. 48 (Feb 22 2013) ISSN: 1479-5876 [Electronic] England
• PMID: 23433486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Antibodies, Neutralizing
• Immunoglobulin G

Topics

• Anti-HIV Agents (administration & dosage, therapeutic use)
• Antibodies, Neutralizing (immunology)
• Antiretroviral Therapy, Highly Active
• Cohort Studies
• Drug Administration Schedule
• Flow Cytometry
• HIV Infections (drug therapy, immunology)
• Humans
• Immunoglobulin G (immunology)