Fig 4. Immunization strategies to initiate and mature CH235 lineage bnAbs.

A strategy is presented to elicit CH235 lineage bnAbs by first priming with an immunogen that is predicted to engage appropriate naïve B cells with high, medium or low relative affinities. Subsequent boosting immunogens would aim to mature the response by driving the somatic mutations required to accommodate N279, G458 and a fully processed glycan shield. The choice of boosting immunogens depends in part on which priming immunogen proves to be optimal for precursor induction. Man₅-enriched immunogens would be produced in GnT1^- cells, and fully glycosylated immunogens would be produced in 293F or equivalent cells, where the cells for both immunogens are approved for GMP manufacturing.