Multiple roles of humoral responses in the control of HIV infection

Spontaneous control of HIV replication has been primarily associated with cellular immune responses. However, it remains multifactorial, and viral determinants, innate and humoral immune responses could be additional relevant contributors. Furthermore, posttreatment control cases reveal new roles for humoral responses. This review describes the direct, indirect and passive roles of humoral responses in HIV control.

New evidence supports the role of the humoral responses in the natural control of HIV. Indeed, a strong association has been reported between polyfunctional humoral responses and slow disease progression, highlighting the active role of both neutralizing and nonneutralizing antibodies in natural control. Moreover, broadly neutralizing antibodies (bNAbs) are being considered as therapeutic interventions to directly or indirectly mediate HIV control in cure strategies. Data from the latest clinical trials show that treatment with bNAbs may induce high-quality CD8 T-cell responses, pointing to bNAbs as a major indirect strategy to induce durable HIV control. Finally, humoral responses can serve as biomarkers for monitoring elite controllers and have been useful to identify stable aviremic controllers, providing new clinical monitoring tools.

Humoral responses are relevant for understanding immune mechanisms of control, for defining therapeutic interventions and for the clinical follow-up of elite controllers.