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.

in vivo, as evidenced by the licensure of several therapeutic antibodies. Another advantage to this approach is that one could simultaneously use numerous anti-idiotypes to stimulate multiple potentially protective lineages. However, it must be recognized that it is unlikely that the injection of a single antiidiotype containing immunogen would induce the production of a protective antibody in situations where high levels of somatic mutation are required (Scheid et al., 2009; Dimitrov, 2010; Pancera et al., 2010; Zhou et al., 2010; Haynes et al., 2012; Mouquet et al., 2012; Jardine et al., 2013; Klein et al., 2013a,b; McGuire et al., 2013; Escolano et al., 2016) . In these situations, successive injections of immunogens containing anti-idiotypes of increasingly mature antibodies may guide antibody maturation toward highly protective antibodies. Alternatively, anti-idiotypes may be better suited for activation of protective antibodies that require less somatic mutation, such as those that can neutralize Middle East respiratory syndrome (Agrawal et al., 2016) and respiratory syncytial virus (Goodwin et al., 2018) , or as the first step in a maturation pathway that includes pathogen-derived antigen in subsequent boosts.