Targeting HIV-1 immune escape mechanisms: Key advances and challenges in HIV-1 vaccine design

Despite numerous efforts, a successful vaccine against HIV-1 remains elusive. An effective vaccine must overcome the virus's sophisticated immune evasion strategies and induce the production of broadly neutralizing antibodies to counteract HIV-1's rapid mutation, replication, and transmission within and between hosts. HIV-1 predominantly evades immune recognition and clearance through mechanisms such as genomic mutations, alterations in envelope protein affinity, the formation of latent viral reservoirs, and interference with major histocompatibility complex class I antigen presentation. Although considerable efforts have focused on generating potent HIV-1 vaccines that elicit bnAbs, the probability of achieving such antibodies remains exceedingly low given the virus's immune-evasive tactics. This review discusses the principal mechanisms of HIV-1 immune evasion and highlights the latest progress in vaccine research, providing fresh perspectives and insights for the design of effective HIV-1 vaccines.