To enrich the global AIDS vaccine pipeline with novel concepts,a number of important scientific challenges must be addressed(fig.l).At the core of these is that natural immune responses to infection do not eradicate HIV in the majority of cases,so it is not clear what a protective immune response should look like or which antigens should be incorporated into a vaccine.Hypervariability of HIV also complicates the selection of antigens.There are many different viral subtypes(clades)to consider,moreover,during the time it takes for a vaccine candidate to be designed,developed and tested clinically,the virus circulating in the population may have significantly evolved.
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