Cytotoxic T Lymphocyte Responses in HIV-1-Infected Long-Term Nonprogressors: Lessons for Vaccine Design

Abstract

Cytotoxic T lymphocytes (CTLs) are considered to play an important role in the containment of HIV-1 infection. Their efficacy is, however, limited as they also continuously select for HIV-1 variants with escape mutations in CTL epitopes. Moreover, it remains to be established whether the preservation of high frequencies of HIV-1-specific CTLs in long-term nonprogressive HIV-1 infection are the cause or consequence of controlled HIV infection. On the positive side, some escape mutations seem to come at a fitness cost to the virus, which may imply that some CTLs, by selecting HIV-1 variants with reduced replication competence, still contribute to a reduced viral load. The implications of current knowledge on HIV-specific cellular immunity for vaccine development will be discussed.

Specific antibody‐dependent cellular cytotoxicity responses associated with slow progression of HIV infection

“…Further, the number of LTSP subjects that generated Vpu peptide‐specific ADCC responses was modest (seven of the 65 subjects, 10·8%). However, this might be expected because multiple other mechanisms, such as HLA class I molecules and CCR5 deletions, have been associated with slow HIV progression . Indeed, 35% of the LTSP subjects tested were CCR5Δ32 heterozygotes and 41% of the LTSP subjects tested had either HLA B27 or B57 alleles.…”