Shedding Light on HIV Vaccine Design
Article Aug 24, 2016
A mathematical model which tracks the rapid coevolution of the human adaptive immune system and viruses during chronic HIV infection has been created, bringing scientists one step closer to understanding the conditions under which highly potent, broadly neutralising antibodies can be produced to help fight long term viral infections.
A small team of scientists from Princeton University and the University of Pennsylvania, USA, focused on the changes in binding interactions between antibody and antigen populations which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection and drift. The model and resultant analysis, which was published last month in PLOS Genetics, identified effective parameters for selection on B-cells during hyper-mutation that enhance their binding and neutralization efficacy, and conversely parameters for selection on viruses to escape antibody binding.
Measuring interactions between antibodies and viruses isolated from different times provided a powerful way to track coevolution, and the team applied their model to interpret ‘time-shifted’, neutralization measurements from two HIV patients and were able to infer modes of immune-viral coevolution. Finally, the team showed that emergence and fixation of a given local antibody lineage is determined by competition between circulating antibody lineages, and that broadly neutralising antibody lineages are more likely to dominate in the context of a diverse viral population.
One of the central challenges in HIV vaccine research is to devise a means to stimulate a cell lineage producing broadly neutralizing antibodies. Studies such as this one help to elucidate the evolutionary processes of the adaptive immune system with a view to one day guiding the production of smarter vaccines against viruses which cause chronic infections such as HIV.
Armit Hourmohammad, Associate Research Scholar at Lewis-Sigler Institute, commented "While our analysis focused on HIV-immune co-evolution, our theoretical framework is general enough to apply to other out-of-equilibrium co-evolutionary scenarios, such as bacteria-phage interactions, or co-evolution of influenza virus in the context of the evolving global immune system."
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