The identification of multiple broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer has facilitated its structural characterization and guided Env immunogen design. Several recent studies constitute progress in utilizing this knowledge for the development of an HIV-1 vaccine that induces bNAbs. Native-like Env trimers can induce autologous NAb responses against resistant (Tier-2) viruses in several animal models. Here we review recent studies aimed at addressing the challenge of driving the strong but narrowly focused NAb responses to Env trimers towards ones with much greater breadth. Among strategies that merit pursuing are using multiple trimers as sequential or simultaneous immunogens, targeting the germline precursors of bNAbs, delivering sequential lineages of trimers derived from infected individuals who developed bNAbs, and presenting trimers as particulate antigens.
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