Table 1.

Env immunogen designs and their effect on neutralizing antibody responses

Immunogen Design	Concept	Immunogens Tested	Result	References
Centralized Sequences	To reduce the genetic distance between immunogens and primary isolates to elicit a more cross reactive response	Group M Consensus	Increased Breadth of NAb Response	[37, 38]
		Subtype B Consensus	Increased NAb Potency Over Wild type Sequences	[41]
		Subtype C Consensus	No Appreciable Increase Nab Response	[39]
		Ancestral B	No Appreciable Increase Nab Response	[40]
		Ancestral C	No Appreciable Increase Nab Response	[39]
Variable Loop Deletions	To make functionally important domains more accessible	V1/V2, V3, & V4 Deletions	No Appreciable Increase Nab Response	[48, 52, 53]
		V2 Deletions	Increased potency and small increases in breadth of NAb Response	[49, 51, 52, 124]
Glycosylation Mutants	To shield irrelevant domains or expose important domains	Hyperglycosylation	Elimination of unwanted Ab specificities No improvement on overall NAb	[61, 62]
		Targeted deletion	Increased breadth and potency of NAb response is some isolates, no effect in others	[63–66]
Envelope Trimers	To better mimic the natural state of functional trimer	Eliminate Env cleavage site	Study and Isolate Dependent	[67, 68]
		Stabilized intermolecular interactions	Inconsistent increases in potency of NAb titers to homologous isolates
		Env trimerized with heterologous motifs	Increased potency of NAb Response	[69, 70, 72]
Epitope Grafting	To make a neutralizable epitope more immunogenic when presented in a different context	MPER Grafts	No increases in NAbs with specificity for graft	[76, 77]