The recently discovered quaternary-specific antibodies PG9 and PG16 neutralize 70 to 80% of circulating human immunodeficiency virus type 1 (HIV-1) strains. determined the structure of PG16 and used chimeric swaps to establish structure-activity relationships. Effective neutralization by these antibodies requires two unusual features, an extensive degree of affinity maturation and a combining region dominated by an axe-shaped subdomain. Barriers to eliciting these two features provide a likely

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... xplanation for the rarity of antibodies like PG9 and PG16. Understanding and overcoming such barriers may form the basis of an effective HIV-1 vaccine.