Viral-Induced Enhanced Disease Illness

Figures

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  Figure 1. Mechanisms of ADE of viral infections. (A) Enhancement on FcγR bearing cells: (1) Viruses-antibody complexes are internalized to cells after antibody Fc-region binding to FcγR on the immune cells. (2) Subversion of the immune system response by reducing Th1 cytokines IL2, TNF-α and IFN-γ, increasing Th2 cytokines IL-10, IL-6, PGE-2 and INF-α, and inhibiting STAT pathway leading to decreased levels IRF and subsequent decrease in the antiviral iNOS. (3) Increased viral replication as a result of suppression of the antiviral response. (B) Enhancement on CR-bearing cells: (1) Formation of virus-antibody complexes. (2) This complex will activate the complement pathway by binding to C1q. Following activation, C2a and C4b proteins are recruited to produce C3 convertase, which in turn hydrolyses C3, to produce C3b. (3) C3b binds to the virus and to complement receptor (CR) on CR bearing cells. (4) Cell lysis and enhanced disease pathology.

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  Figure 2. A general strategy for designing an efficacious vaccine that overcomes ADE requires: 1, Identifying the right epitope that elicits functional protective antibodies: An effective vaccine should be designed using conserved and functional epitopes, which usually exist in the pre-fusion conformation of the surface glycoproteins; 2, Selection of the right adjuvant that can direct the immune system toward a balanced Th1/Th2 response; and 3, A carful and accurate assessment of the efficacy and safety of the vaccine at different doses in pre-clinical and clinical trials.