Design and preclinical development of a recombinant protein and DNA plasmid mixed format vaccine to deliver HIV-derived T-lymphocyte epitopes.
Coordinated interactions between helper and cytotoxic T-lymphocytes (HTL and CTL) are needed for optimal effector cell functions and the establishment of immunological memory. We, therefore, designed a mixed format vaccine based on the use of highly conserved HIV-derived T-lymphocyte epitopes wherein the HTL epitopes were delivered as a recombinant protein and the CTL epitopes which were encoded in a DNA vaccine plasmid. Immunogenicity testing in HLA transgenic mice and GLP preclinical safety testing in rabbits and guinea pigs were used to document the utility of this approach and to support Phase 1 trial clinical testing. Both vaccine components were immunogenic and safely co-administered.
Walker
Leslie E
LE
Pharmexa Inc., San Diego, CA, USA.
Vang
Lo
L
Shen
Xuefei
X
Livingston
Brian D
BD
Post
Penny
P
Sette
Alessandro
A
Godin
C Steven
CS
Newman
Mark J
MJ
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006168:Guinea Pigs; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D011994:Recombinant Proteins; D019444:Vaccines, DNA