HIV frequently escapes CD8 T cell responses, leading to the accumulation of viral adaptations. We recently demonstrated that, during chronic HIV infection, adapted epitopes can promote dendritic cells (DC) maturation through direct CD8 T cell interactions and lead to enhanced HIV -infection of CD4 T cells. Here, we sought to determine the role of such adaptations following HIV MRKAd5 vaccination. We observed that vaccine-induced adapted epitope specific CD8 T cells promoted higher levels of DC maturation than non-adapted ones and these matured DCs significantly enhanced HIV -infection. The latter was associated with higher levels of IL5 and IL13 and a lower level of CXCL5, which have been shown to impact DC mat... More
HIV frequently escapes CD8 T cell responses, leading to the accumulation of viral adaptations. We recently demonstrated that, during chronic HIV infection, adapted epitopes can promote dendritic cells (DC) maturation through direct CD8 T cell interactions and lead to enhanced HIV -infection of CD4 T cells. Here, we sought to determine the role of such adaptations following HIV MRKAd5 vaccination. We observed that vaccine-induced adapted epitope specific CD8 T cells promoted higher levels of DC maturation than non-adapted ones and these matured DCs significantly enhanced HIV -infection. The latter was associated with higher levels of IL5 and IL13 and a lower level of CXCL5, which have been shown to impact DC maturation, as well as a lower level of CXCL16. Finally, we observed that vaccine recipients with high HLA-I associated adaptation became HIV infected more quickly. Our results offer another possible mechanism for the enhanced infection among MRKAd5 vaccinees. Despite the well-established contribution of CD8 T cells in HIV control, prior CD8 T cell-based HIV vaccines have failed to demonstrate any efficacy in preventing viral infection. One such vaccine, known as the MRKAd5 vaccine, showed a potential increased risk of viral infection among vaccine recipients. However, the underlying mechanism(s) remains unclear. In this study, we observed vaccine recipients with high adaptation to their HLA-I were associated with an increased HIV infection risk than the others. Similar to what we observed in HIV infection in the prior study, adapted epitope specific CD8 T cells obtained from vaccine recipients exhibit a greater capacity in facilitating viral infection by promoting dendritic cell maturation. Our findings provide a possible explanation for the enhanced viral acquisition risk among MRKAd5 vaccine recipients and highlight the importance to optimize the vaccine design with consideration of HLA-I associated HIV adaptation.
