Table 1.

Summary of HIV bNAb Fv engineering strategies.

↑ Potency and/or breadth of neutralization	Directed evolution	b12	↑ Affinity ~400x & ↑ breadth	139,140
		m9	↑ Breadth through sequential antigen panning	141
	Rational mutations	PG9_N100(F)Y	Stabilize CDR-H3 in active conformation	142
		NIH45-46_G54W, VRC07-523	Improve Hydrophobic interactions	65, 143
		45–46m2	Leverage glycan contacts	144
		45–46m2, 45–46m7, 45–46m25, and 45–46m28	Avoid steric clashes between Ab & Ag escape variants	144
		10–1074&PGT121, PG9-PG16-RSH, 4E10&10E8	Combine CDRs of bNAbs targeting similar epitopes	60, 69, 145
		CD4-Ig	Replace Fv with extracellular domain of CD4	147–150, 153, 154
Restrict viral escape	Rational mutations	45–46m7, 45–46m25, and 45–46m28	Bias antigen escape towards detrimental mutations	144
	Combining mAbs		Combine mAbs with complementary resistance patterns	156–158
	Target host cellular receptors	Ibalizumab (iMAb)	Target CD4 receptor	159–162
		PRO140	Target CCR5 coreceptor	159, 163–166
		bNAb + iMab / PRO140	Bispecifics combining bNAbs with iMab or PRO140	167, 168
↓Polyreacvity/aggreggation propensity	Rational mutations	NIH45-46_G54W, 10E8	Determine acceptable mutations based on clonal relatives	65, 143