Michael Roche

This session described Immune responses critical for viral control. Presentations included the role of dendritic cells in the first interactions with HIV in the anogenital mucosa; mechanisms of natural killer cell viral control; and harnessing ADCC responses for protection from HIV infection.

Tony Cunningham (Westmead Institute) described the role of dendritic cells in HIV infection and disease. CD11c+ conventional dendritic cells in anogenital mucosa support high levels of HIV infection and efficiently transfer HIV to tissue resident memory CD4+ T cells. Langerhans cells and other dendritic cells also transport HIV to CD4+ T cells via type C lectin receptors, possibly through CLEC5A. Angelique Hölzemer (Leibniz Institut) provided data on a potential new role for NK cells to control HIV infection. Many receptors recognised by NK cells are downregulated on HIV-infected cells except for HLA-F. This receptor was shown to be upregulated on CD4+ T cells from people with HIV and is also upregulated on activated CD4+ T cells. It was shown that NK cells can recognise HLA-F through the KIR3DS1 receptor and lead to killing of the HLA-F positive cell. Guido Ferrari (Duke University) discussed the role of Antibody-dependent cellular cytotoxicity (ADCC) in HIV infection, and how it might best be harnessed for mediating protection from infection. Trials have shown that delaying a boost can improve ADCC responses although typically only against vaccine matched virus. Studies in non-human primates with antigen diversified vaccines show promise to induce cross-protection.

For future vaccine studies, time, multiple boosting and antigenic diversity will be needed to develop broadly neutralising and non-neutralising antibody functions. Prophylactic vaccines must deploy immune effectors in the mucosa rapidly to block DC transfer. Blocking type C lectins may be a useful approach in microbicides to inhibit dendritic cell transfer to CD4+ T cells. NK cells controlling CD4+ T cell activation is a promising finding for immune control of HIV replication and associated inflammation. This is particularly exciting as IL-15 superagonists – currently in clinical trials for HIV cure - enhance NK cell cytotoxicity and drive KIR3DS1 expression.