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For HIV vaccine study, scientists build pooled variant library using automated DNA synthesis

March 24, 2021

The quest for an effective vaccine against HIV has spanned decades. While the vaccine itself remains elusive, researchers are making important strides in figuring out how best to design and develop it. Recently, scientists from Duke University and NIH’s Vaccine Research Center released a preprint describing their work characterizing the broadly neutralizing antibodies that will be required for an effective vaccine. The team used the BioXp™ system from Telesis Bio for key components of this project.

In the preprint, lead author Olivia Swanson and collaborators report “a new approach that relies on computational modeling to identify the functionally important somatic mutations present in HIV [broadly neutralizing antibodies] and a strategy to identify and validate candidate immunogens that select antibodies with these mutations in vitro.”

The team reviewed the many acquired mutations characteristic of HIV antibodies to identify the minimal subset required for the intended response. In this case, just 12 of the 42 mutations analyzed in a specific antibody lineage were needed to achieve potency. They then designed an antibody containing only those mutations, positing that it represented an “evolutionary path that is shorter and less complex to induce by vaccination.”

In addition, the scientists came up with a new immunogen design method “that relies on high-throughput screening of antibody libraries to identify envelopes that interact with DH270.6-derived antibodies through the key acquired mutation,” they write.

For this project, researchers deployed the automated BioXp™ system for DNA synthesis of a pooled oligo library. The library was then sorted according to binding affinity for five HIV envelopes, and the best performers were sequenced to compare enrichment levels of key mutations.

“This work illustrates a general approach to identify key functional mutations… and describes a high-throughput method to rationally discover immunogens that target antibody functional mutations,” the authors report.

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