In SCID-hu Mice, Passive Transfer of a Humanized Antibody Prevents Infection and Atrophic Change of Medulla in Human Thymic Implant due to Intravenous Inoculation of Primary HIV-1 Isolate

Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity....

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-01, Vol.160 (1), p.69-76
Main Authors: Okamoto, Yukari, Eda, Yasuyuki, Ogura, Atsuo, Shibata, Shinwa, Amagai, Takashi, Katsura, Yoshimoto, Asano, Toshihiko, Kimachi, Kazuhiko, Makizumi, Keiichi, Honda, Mitsuo
Format: Article
Language:English
Subjects:
Adult
AIDS/HIV
Amino Acid Sequence
Animals
Antibodies, Viral - chemistry
Antibodies, Viral - immunology
Epitope Mapping
HIV Envelope Protein gp120 - chemistry
HIV Envelope Protein gp120 - immunology
HIV Infections - prevention & control
Humans
Immunization, Passive
Male
Mice
Mice, SCID
Molecular Sequence Data
Neutralization Tests
Peptides - immunology
Recombinant Fusion Proteins
Thymus Gland - cytology
Thymus Gland - pathology
Thymus Gland - transplantation
Thymus Gland - virology
Transplantation, Heterologous
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Summary:Using SCID-hu mice, it was tested whether humanized mAb Rmu5.5 could prevent infection by HIV-1 i.v. inoculation. The Ab that recognizes the IHIGPGRAFYT motif in the principal neutralizing determinant (PND) of HIV(MN), as well as the original mouse mAb mu5.5, neutralized HIV(MN) with high activity. Seven primary field isolates from Japanese hemophiliacs seropositive for HIV-1 clade B were compared for their reactivities to Rmu5.5. Rmu5.5 was effective, particularly against the viruses that matched amino acid sequences of the PND region of HIV-1, and it completely neutralized primary isolates. Moreover, the passive transfer of the Ab elicited protection against challenge by the primary isolates in SCID-hu or hu-PBL-SCID mice after i.v. inoculation with the virus by both quantitative PCR and PBMC-based virus isolation in vitro. Further, inoculation with the Ab also prevented the atrophic change in the medulla of the thymic transplant that was induced by i.v. inoculation of the virus. Thus, the humanized neutralizing Ab Rmu5.5 appears to protect SCID-hu mice from infection by primary field isolates.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.1.69