TY - JOUR
T1 - Long peptides induce polyfunctional T cells against conserved regions of HIV-1 with superior breadth to single-gene vaccines in macaques
AU - Rosario, Maximillian
AU - Bridgeman, Anne
AU - Quakkelaar, Esther D.
AU - Quigley, Maire F.
AU - Hill, Brenna J.
AU - Knudsen, Maria L.
AU - Ammendola, Virginia
AU - Ljungberg, Karl
AU - Borthwick, Nicola
AU - Im, Eung Jun
AU - McMichael, Andrew J.
AU - Drijfhout, Jan W.
AU - Greenaway, Hui Yee
AU - Venturi, Vanessa
AU - Douek, Daniel C.
AU - Colloca, Stefano
AU - Liljeström, Peter
AU - Nicosia, Alfredo
AU - Price, David A.
AU - Melief, Cornelis J.M.
AU - Hanke, Tomáš
PY - 2010/7
Y1 - 2010/7
N2 - A novel T-cell vaccine strategy designed to deal with the enormity of HIV-1 variation is described and tested for the first time in macaques to inform and complement approaching clinical trials. T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most conserved regions of the HIV-1, proteome and thus both targets diverse clades in the population and reduces the chance of escape in infected individuals, was delivered using six different vaccine modalities: plasmid DNA (D), attenuated human (A) and chimpanzee (C) adenoviruses, modified vaccinia virus Ankara (M), synthetic long peptides, and Semliki Forest virus replicons. We confirmed that the initial DDDAM regimen, which mimics one of the clinical schedules (DDDCM), is highly immunogenic in macaques. Furthermore, adjuvanted synthetic long peptides divided into sub-pools and delivered into anatomically separate sites induced T-cell responses that were markedly broader than those elicited by traditional single-open-reading- frame genetic vaccines and increased by 30% the overall response magnitude compared with DDDAM. Thus, by improving both the HIV-1-derived immunogen and vector regimen/delivery, this approach could induce stronger, broader, and theoretically more protective T-cell responses than vaccines previously used in humans.
AB - A novel T-cell vaccine strategy designed to deal with the enormity of HIV-1 variation is described and tested for the first time in macaques to inform and complement approaching clinical trials. T-cell immunogen HIVconsv, which directs vaccine-induced responses to the most conserved regions of the HIV-1, proteome and thus both targets diverse clades in the population and reduces the chance of escape in infected individuals, was delivered using six different vaccine modalities: plasmid DNA (D), attenuated human (A) and chimpanzee (C) adenoviruses, modified vaccinia virus Ankara (M), synthetic long peptides, and Semliki Forest virus replicons. We confirmed that the initial DDDAM regimen, which mimics one of the clinical schedules (DDDCM), is highly immunogenic in macaques. Furthermore, adjuvanted synthetic long peptides divided into sub-pools and delivered into anatomically separate sites induced T-cell responses that were markedly broader than those elicited by traditional single-open-reading- frame genetic vaccines and increased by 30% the overall response magnitude compared with DDDAM. Thus, by improving both the HIV-1-derived immunogen and vector regimen/delivery, this approach could induce stronger, broader, and theoretically more protective T-cell responses than vaccines previously used in humans.
KW - HIV vaccines
KW - Macaques
KW - Prime-boost
KW - Synthetic long peptides
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=77954097759&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954097759&partnerID=8YFLogxK
U2 - 10.1002/eji.201040344
DO - 10.1002/eji.201040344
M3 - Article
C2 - 20468055
AN - SCOPUS:77954097759
SN - 0014-2980
VL - 40
SP - 1973
EP - 1984
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -