Remodeling of dynamic structures of HIV-1 envelope proteins leads to synthetic antigen molecules inducing neutralizing antibodies.
A synthetic antigen targeting membrane-fusion mechanism of HIV-1 has a newly designed template with C3-symmetric linkers mimicking N36 trimeric form. The antiserum produced by immunization of the N36 trimeric form antigen showed structural preference in binding to N36 trimer and stronger inhibitory activity against HIV-1 infection than the N36 monomer. Our results suggest an effective strategy of HIV vaccine design based on a relationship to the native structure of proteins involved in HIV fusion mechanisms.
Nakahara
Toru
T
Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kandasurugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Nomura
Wataru
W
Ohba
Kenji
K
Ohya
Aki
A
Tanaka
Tomohiro
T
Hashimoto
Chie
C
Narumi
Tetsuo
T
Murakami
Tsutomu
T
Yamamoto
Naoki
N
Tamamura
Hirokazu
H
D016915:AIDS Vaccines / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000276:immunology*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D002460:Cell Line; D015195:Drug Design; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D018716:Molecular Mimicry; D011487:Protein Conformation
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015488:HIV Antigens; D015700:HIV Envelope Protein gp41