@article{fdi:010073368,
  title = {{A} 30-year journey of trial and error towards a tolerogenic {AIDS} vaccine},
  author = {{A}ndrieu, {J}.{M}. and {L}u, {W}ei {L}ouis},
  editor = {},
  language = {{ENG}},
  abstract = {{S}ince 1985, we have tested several immunological approaches to suppressing {HIV} replication in {HIV}-infected patients and to prevent {HIV} acquisition in uninfected people. {H}ere, after briefly reviewing our studies on immunosuppressive treatments and therapeutic dendritic cell-based therapies, we examine in more detail our work on the tolerogenic vaccines we developed against {AIDS} in {C}hinese macaques. {T}he vaccine consisted of inactivated {SIV}mac239 particles adjuvanted with the {B}acillus of {C}almette and {G}uerin ({BCG}), {L}actobacillus plantarum ({LP}), or {L}actobacillus rhamnosus ({LR}). {W}ithout adjuvant, the vaccine administered by the intragastric route induced the usual simian immunodeficiency virus ({SIV})-specific humoral immune responses but no post-challenge protection. {I}n contrast, out of 24 macaques that were immunized with the adjuvanted vaccine and challenged intrarectally with {SIV}mac239 or {SIVB}670, 23 were sterilely protected for up to 5 years, while all control macaques were infected. {O}n the other hand, all macaques of {I}ndian origin that were immunized with the same adjuvanted vaccine were not protected. {W}e then discovered that vaccinated {C}hinese macaques developed a previously unrecognized class of non-cytolytic {MHC}-{I}b/{E}-restricted {CD}8(+) {T} cells (or {CD}8(+) {T}-{R}egs) that suppressed the activation of {SIV} {RNA}-infected {CD}4(+) {T} cells and thereby inhibited the (activation-dependent) reverse transcription of the virus and prevented the establishment of {SIV} infection. {F}inally, we found a similar population of {HLA}-{E}-restricted {CD}8(+) {T}-{R}egs in human elite controllers (a small group of {HIV}-infected patients whose viral replication is naturally inhibited). {E}x vivo, their {CD}8(+) {T}-{R}egs suppressed viral replication in the same manner as those of vaccinated {C}hinese macaques. {I}t is noteworthy that all of these elite controllers had a homo- or heterozygous {HLA}-{B}w4-80{I} genotype. {T}aking into account the longevity and the high percentage of vaccine-protected {C}hinese macaques together with the concomitant identification of a robust ex vivo correlate of protection and the discovery of similar {CD}8(+) {T}-{R}egs in human elite controllers, preventive and therapeutic {HIV} vaccines should be envisaged in humans.},
  keywords = {{CHINE}},
  booktitle = {{I}n honor of {M}arc van {R}egenmortel},
  journal = {{A}rchives of {V}irology},
  volume = {163},
  numero = {8},
  pages = {2025--2031},
  ISSN = {0304-8608},
  year = {2018},
  DOI = {10.1007/s00705-018-3936-1},
  URL = {https://www.documentation.ird.fr/hor/fdi:010073368},
}