Table 2.

Major obstacles encountered for the development of a successful vaccine against HIV‐1

Lack of suitable animal model systems

Hypervariability of the virus, particularly because of the extensive mutations in viral protein env and others

Extensive glycosylation and surface masking of viral proteins (e.g., gp120 and gp41)

Inaccessibility of antibody epitopes (e.g., CD4‐binding site is a recessed cavity)

Reduced antigen presentation (because of downregulation of human leukocyte antigen class I and development of antibodies against gp120 CD4‐binding site)

Decline in CD4 T‐cell numbers and dysfunction

Inability to induce broadly neutralizing antibodies against the virus

Rapid emergence of CTL escape mutants

Population‐specific variability in host genetic and immunologic response factors

Synergistic opportunistic infections and complications thereof