Maturation of the humoral immune response to HIV-1 infection

Abstract

We have examined the maturation of the humoral immune response to human immunodeficiency virus (HIV-1) infection, by correlating the individual antibody isotype profiles (titre, affinity and epitope specificity) with time elapsed following initial infection. The methodology we have used includes isotype specific Western blots, antibody isotype and antigen specific enzyme immunoassays and the analysis of direct antibody-antigen interaction using surface plasmon resonance. We have analysed sequential samples obtained from individuals undergoing serocon-version, individuals placed on highly active anti-retroviral treatment (HAART) early following infection and individuals who have undertaken structured treatment interruptions (STI) following early HAART intervention. As the humoral immune response to HIV develops we have observed different antibody isotypes, directed to discrete HIV antigens, occurring at different time points following infection, and often these interactions only occur transiently. The administration of HAART decreases the viral load to undetectable levels. This loss of antigenic stimulation delays maturation of the humoral immune response. Re-exposure to viral antigens during STI stimulates continuing maturation of the immune response. The humoral immune profiles generated in response to HIV-1 infection may assist in providing insight into the best strategies to employ for effective vaccines and potential correlates of disease progression.