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.

There are many pathogens, such as HIV-1, respiratory syncytial virus, and influenza virus, for which the development of a protective vaccine has been elusive despite decades of effort. In many cases, the failure does not appear to be an absolute inability of the immune system to produce protective antibodies, since they have been characterized in some infected individuals (Beeler and van Wyke Coelingh, 1989; Burton et al., 1991; Okuno et al., 1993; Johnson et al., 1997; Karron et al., 1997; Scanlan et al., 2002; Kashyap et al., 2008; Throsby et al., 2008; Ekiert et al., 2009 Ekiert et al., , 2011 Scheid et al., 2009 Scheid et al., , 2011 Sui et al., 2009; Walker et al., 2009 Walker et al., , 2011 Wu et al., 2010; Corti et al., 2011; Dreyfus et al., 2012 Dreyfus et al., , 2013 Huang et al., 2012 Huang et al., , 2014 Magro et al., 2012; Mouquet et al., 2012; Liao et al., 2013; Ngwuta et al., 2015) . It is not entirely clear why traditional vaccine development approaches have failed to induce similar protective antibodies, but mounting evidence suggests that protective vaccines for these pathogens will likely need to stimulate specific lineages of antibodies targeting defined epitopes (Pantaleo and Koup, 2004; Rappuoli et al., 2016; Lang et al., 2017; Robbiani et al., 2017; Goodwin et al., 2018; Kwong and Mascola, 2018) . In contrast, traditional vaccines generally stimulate polyclonal antibody responses against whole pathogens, or large subunits from pathogens, rather than focus the immune response toward known protective epitopes.