Humoral dysregulation among injection drug users: implications for HIV vaccine strategies

The primary objective of a preventative HIV vaccine is the induction of a persistent humoral response that mediates sterilizing immunity. Although modest, yet encouraging, a reduction in infections in low-risk individuals was obtained in the RV144 HIV vaccine efficacy trial; for high-risk individuals, including injection drug users (IDU) no substantial reduction in infection has been observed in efficacy trials. The impact of injection drug use on humoral responses is poorly defined, particularly in the context of HIV prevention. Through a cross-sectional assessment of peripheral B cells and plasma antibodies, we have identified substantial alterations in the HIV-/HepC- active heroin IDU population. IDU exhibited significantly increased total B cells compared to healthy subjects, that were associated with significantly increased memory B cells and plasmablasts. Additionally, although plasma total IgG levels were similar between IDU and healthy subjects, IDU had significantly higher titers of IgG3 and IgG4 subclass plasma antibodies. Total IgM plasma antibodies were also increased in IDU. This humoral dysregulation may be the consequence of a pro-inflammatory environment as evident by significantly increased plasma sCD40L in IDU. These results demonstrate extensive differences in the steady-state humoral profile of IDU, which could have the potential to severely influence the quality of the B cell and antibody response, and ultimate efficacy of future HIV vaccine strategies.