Postinfection passive transfer of KD-247 protects against simian/human immunodeficiency virus-induced CD4+ T-cell loss in macaque lymphoid tissue.
BACKGROUND
Preadministration of high-affinity humanized anti-HIV-1 mAb KD-247 by passive transfer provides sterile protection of monkeys from heterologous chimeric simian/human immunodeficiency virus infection.


METHODS
Beginning 1 h, 1 day, or 1 week after simian/human immunodeficiency virus-C2/1 challenge (20 50% tissue culture infective dose), mature, male cynomolgus monkeys received multiple passive transfers of KD-247 (45 mg/kg) on a weekly basis for approximately 2 months. Concentrations and viral loads were measured in peripheral blood, and CD4 T-cell counts were examined in both peripheral blood and various lymphoid tissues.


RESULTS
Pharmacokinetic examination revealed similar plasma maintenance levels ranging from 200 to 500 microg/ml of KD-247 in the three groups. One of the six monkeys given KD-247 could not maintain these concentrations, and elicitation of anti-KD-247 idiotype antibody was suggested. All monkeys given KD-247 exhibited striking postinfection protection against both CD4 T-cell loss in various lymphoid tissues and atrophic changes in organs compared with control group animals treated with normal human immunoglobulin G. The KD-247-treated groups were also partially protected against plasma viral load elevation in peripheral blood samples, although the complete protection previously reported with preadministration of this mAb was not achieved.


CONCLUSIONS
Postinfection passive transfer of humanized mAb KD-247 with strong neutralizing capacity against challenged virus simian/human immunodeficiency virus-C2/1 protected CD4 T cells in lymphoid organs.
Murakami
Toshio
T
The Chemo-Sero-Therapeutic Research Institute (Kaketsuken), Kyokushi, Kikuchi, Kumamoto, Japan.
Eda
Yasuyuki
Y
Nakasone
Tadashi
T
Ami
Yasushi
Y
Someya
Kenji
K
Yoshino
Naoto
N
Kaizu
Masahiko
M
Izumi
Yasuyuki
Y
Matsui
Hajime
H
Shinohara
Katsuaki
K
Yamamoto
Naoki
N
Honda
Mitsuo
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D001284:Atrophy / Q000517:prevention & control; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D007116:Immunization, Passive; D008221:Lymphoid Tissue / Q000276:immunology*; D008252:Macaca fascicularis; D010446:Peptide Fragments / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000097:blood / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D013950:Thymus Gland / Q000473:pathology; D019562:Viral Load
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral; D018449:SAIDS Vaccines