Ex vivo neutralization of HIV-1 quasi-species by a broadly reactive humanized monoclonal antibody KD-247.
By immunizing mice sequentially with six different V3 peptides we obtained a murine monoclonal antibody (MAb) C25, and its humanized counterpart KD-247. The MAb recognizes the sequence IGPGRA at the tip of the V3 loop and displays broad neutralizing activity against a variety of HIV-1 isolates. KD-247 was tested in an ex vivo neutralization assay to determine its capability to contain the spread of a quasi species population of clade B HIV-1 derived from two patients. The epitope of KD-247 was generally matching with the V3 sequences of various clones isolated from plasma and peripheral blood mononuclear cells (PBMC) of two patients. Complete or strong inhibition of viral replication was observed when the patients' PBMC were cultured with a high concentration of KD-247. Some neutralization escape variants, which had mutations in the V3 or outside of the V3 loop, emerged only at a low concentration of the MAb. These results suggest that KD-247 could be a good candidate for immunotherapy against HIV-1 in vivo.
Matsushita
Shuzo
S
Division of Clinical Retrovirology and Infectious Diseases, Center for AIDS Research, Kumamoto University, Japan. shuzo@kaiju.medic.kumamoto-u.ac.jp
Takahama
Soichiro
S
Shibata
Junji
J
Kimura
Tetsuya
T
Shiozaki
Koichi
K
Eda
Yasuyuki
Y
Koito
Atsushi
A
Murakami
Toshio
T
Yoshimura
Kazuhisa
K
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D018604:Epitope Mapping; D015483:HIV Antibodies / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests / Q000379:methods; D010446:Peptide Fragments / Q000276:immunology*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments