Figure 2.

Proposed mechanism to explain enhancement of hRSV-induced disease following FI-hRSV vaccination. Formalin hRSV inactivation produces a non-infectious virus with a high proportion of post-fusion conformation epitopes in the F protein (Post-F) (1). The inactivated virus is then phagocyted by B cells (2) that can present hRSV antigens to T cells in the context of MHC molecules (3). The interaction between B and T cells allows the differentiation of B cells into plasma cells that generate antibodies against the post-fusion conformation of the hRSV F protein (4). Such antibodies failed to neutralize hRSV infection but also may enhance the infection of FcγR bearing cells such as DCs. When infection by hRSV occurs, the low neutralizing antibodies induced by the FI-hRSV vaccine can form immune-complexes (ICs) with hRSV (5) that leads to the activation of Fc-gamma receptors expressed on the surface of DCs (6). Subsequently, an impaired DC-mediated T cell activation (7) can induced CD4⁺ T cells with a Th2-biased phenotype that promotes lung damage (8). Furthermore, low secretion of IL-2 by CD4⁺ cells activated by hRSV-IC-loaded DCs can lead to a poor memory response that contributes to hRSV re-infection (9).