Immune Immune 3: Two epitopes, four serotypes, and a partridge in a pear tree
Dec 16, 2017
Explore the complexities of dengue virus vaccines and the challenges posed by antibody-dependent enhancement. The discussion dives into the design flaws of Dengvaxia, revealing why it can worsen disease in certain cases. Transitioning to Zika, the hosts delve into the promising research on bispecific monoclonal antibodies and their therapeutic implications, including innovative engineering techniques to improve efficacy. They also touch on listener queries, productivity tips, and a stunning polar bear video, making for an engaging blend of science and fun.
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Antibodies Can Make Dengue Worse
- Dengue secondary infections can cause severe disease via antibody-dependent enhancement (ADE) when non-neutralizing antibodies help virus enter Fc-receptor cells.
- Vaccine-induced antibodies that are subneutralizing can similarly sensitize seronegative recipients to worse disease upon later exposure.
T Cells Matter For Dengue Protection
- Protection against severe dengue likely requires both high neutralizing antibody titers and T cell responses, especially to non-structural proteins.
- Dengvaxia uses a yellow fever backbone and lacks dengue non-structural T-cell epitopes, which may reduce durable protection and contribute to risk in seronegatives.
Limit Dengvaxia Use To Seropositives Or Older Ages
- Countries should prioritize vaccinating populations with prior dengue exposure or use serology to screen recipients before using Dengvaxia.
- If screening is infeasible, restricting vaccination to older age groups with likely prior infection reduces risk.