Antibody-Dependent Cellular Cytotoxicity and NK Cell-Driven Immune Escape in HIV Infection: Implications for HIV Vaccine Development

Table 1

Key escape papers.

Immune response	Hypothesis	Result	Ref.
CTL based	HLA-B*57/B*5801 CTL escape mutations in Gag impacts viral replication in vivo	Reductions in relative replication capacity reduce “viral fitness”	[20]
	CTL escape mutations in Env do not result in reduced viral fitness	Escape mutations within Env-specific CTL are epitopes evident but no correlation with reduced SIV replication	[25]
	Step HIV-1 vaccine trial exerts selective CTL pressure on HIV-1	Extended sequence divergence for vaccine recipients who become infected suggests vaccine-induced CTL imparted significant immune pressure; Gag-84 most significant signature site	[36]
Nab based	Evolving “glycan shield” mechanism prevents Nab binding	Env gene mutations in escape virus sparse; Escape mutations did not map to known epitopes; Efficient neutralization requires potent, high titres	[54]
	Continual selection of Nab escape variants occurs	All previous viral isolates, but not concurrent isolate, are recognised by concurrent Nab	[7]
	Passive transfer of human neutralizing monoclional antibodies delays HIV-1 rebound post-antiretroviral therapy	2G12 monoclonal was crucial for transient in vivo effect of Nab cocktail but immune escape resulted	[55]
ADCC based	Immune pressure from HIV-specific ADCC results in immune-escape variants	ADCC causes escape in multiple epitopes and evolves over timeADCC antibodies forcing immune escape can be non-eutralizing	[9]
	NK cells apply immunological pressure on HIV-1 through direct killing of infected cells	HIV-1 selects KIR2DL2+ virus mutations that result in reduced antiviral activity of NK cells	[85]