Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes

Bancroft, Tara; DeBuysscher, Blair L.; Weidle, Connor; Schwartz, Allison; Wall, Abigail; Gray, Matthew D.; Feng, Junli; Steach, Holly R.; Fitzpatrick, Kristin S.; Gewe, Mesfin M.; Skog, Patrick D.; Doyle-Cooper, Colleen; Ota, Takayuki; Strong, Roland K.; Nemazee, David; Pancera, Marie; Stamatatos, Leonidas; McGuire, Andrew T.; Taylor, Justin J.

Unfortunately, bNAbs have not been elicited by vaccination in humans, despite the use of diverse recombinant Env-derived immunogens and immunization schemes (Burton et al., 2004; Cohen and Dolin, 2013; Schiffner et al., 2013) . Recent advances in the amplification of antibody genes from individual B cells have revealed that bNAbs often require extensive somatic mutation to achieve broad and potent neutralizing activity (Scheid et al., 2009; Dimitrov, 2010; Klein et al., 2013a; Kwong et al., 2013; Mascola and Haynes, 2013; West et al., 2014) . Although mutated bNAbs are capable of broad Env recognition and virus neutralization, most inferred germline bNAb variants do not display reactivity with any Env variant tested, which led us and others to propose that one reason for the lack of bNAb elicitation through immunization is the lack of stimulation of B cells expressing bNAb progenitor B cell receptors (BCRs) by Env-based immunogens (Xiao et al., 2009; Hoot et al., 2013; Jardine et al., 2013; McGuire et al., 2013; Andrabi et al., 2015; Zhou et al., 2015; Gorman et al., 2016) .