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What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Lessons from the Antibody Response to HIV-1.

Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.

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