ABSTRACT
All biotherapeutics have the potential to generate anti-drug antibodies (ADAs) in patients. The main factors leading to an immune response are thought to be product, treatment and patient related. In this review, reasons for the formation of ADAs, and particularly neutralizing antibodies (NAbs), are considered, with a focus on IFN-ß as a well-studied example. The time course for the production of NAbs, the measurement of NAbs, the defining of IFN-ß responders and non-responders, the implications for disease progression in patients, and future methods for avoiding the production of ADAs and of tolerizing patients are considered.
Subject(s)
Drug Resistance/immunology , Immunologic Factors/immunology , Interferon-beta/immunology , Antibody Formation , Humans , Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunologyABSTRACT
We developed highly expressing clade B and AE DNA and envelope protein (Env) vaccines for evaluation in mice and macaques as DNA prime/protein boost regimens. High levels of Env-specific antibodies were induced in mice, albeit with limited neutralizing activity in vitro. A combined clade B and AE regimen induced high titer Env-specific antibody in two pigtail macaques that neutralized several strains of HIV-1. However, upon mucosal challenge with SHIV(SF162P3) no protection from infection was observed. Although the vaccines tested provide a platform for inducing robust humoral immunity, further refinements to broaden coverage against divergent strains and induce mucosal immunity are needed.
