Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication.

Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, Carol I.; Levine, Cindy; Letvin, Norman L.

doi:10.1073/pnas.88.1.120

Cited by 22 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports showed that immunization of rhesus macaques with soluble extracellular human CD4 (D1D4) in the absence of gp120 elicited antibodies that cross-reacted with macaque cells (84,85). Chimpanzees immunized with soluble human CD4 D1D4 developed antibodies reactive with digitonin-treated, but not untreated, chimpanzee lymphocytes (86).…”

Section: Discussionmentioning

confidence: 99%

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

Schwartz

Prado

Misamore

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

؉ T cell staining, and temporal trends in T cell subset frequencies served to assess whether anti-CD4 autoantibody responses were elicited by vaccination. We find that immunization with multiple high doses of rhFLSC did not elicit detectable antibody titers despite robust responses to rhFLSC. In accordance with these findings, immunized animals had no changes in circulating CD4 ؉ T cell counts or evidence of autoantibody reactivity with cell surface CD4 on primary naive macaque T cells. Collectively, these studies show that antigens using CD4 sequences to stabilize transition state gp120 structures are unlikely to elicit autoimmune antibody responses, supporting the advancement of gp120-CD4 complexbased antigens, such as FLSC, into clinical testing.

show abstract

Section: Discussionmentioning

confidence: 99%

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

Schwartz

Prado

Misamore

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…We have shown (14) that the tolerance of the rhesus monkey to self-CD4 can be broken by immunization with human rsCD4. Thus, immunization of the monkey with a human CD4 molecule generated an antibody response to epitopes defined by amino acids specific for monkey CD4 as well as to human CD4 epitopes.…”

Section: Discussionmentioning

confidence: 99%

“…We have demonstrated (13) an improvement in SIVmac-infected rhesus monkeys during and immediately after 50 days of parenteral treatment with human rsCD4. However, a number of observations made during the course of these studies suggested that rsCD4 may have mediated at least some of the clinical improvement in these monkeys by a mechanism other than direct competition for virus binding (14). While human rsCD4 did not efficiently inhibit SIVmac replication in vitro in rhesus monkey lymphocytes and macrophages, antibody in the plasma of the rsCD4-treated animals did.…”

mentioning

confidence: 94%

See 1 more Smart Citation

Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

Watanabe¹,

Levine

Shen

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIV,)-infected rhesus monkey to explore another possible therapeutic application of CD4 in AIDS-the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVnc-infected rhesus monkeys immunized with human rsCD4 developed not only an antihuman CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIV,,,C could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals.

show abstract

“…Several recombinant CD4-derived candidates have been developed as anti-HIV therapeutics (7). In general, poor bioavailability, rapid degradation, and antigenicity affect the utility of proteinaceous pharmaceuticals (8,9). The dissection of complex proteins into small synthetic conformationally restricted functional subunits may overcome these problems.…”

mentioning

confidence: 99%

Design and synthesis of a CD4 beta-turn mimetic that inhibits human immunodeficiency virus envelope glycoprotein gp120 binding and infection of human lymphocytes.

Chen

Chrusciel

Nakanishi

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Poor bioavailability, rapid degradation, antigenicity, and high cost often limit the use of proteinaceous pharmaceuticals. One goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of complex proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. We have developed a reverse-turn mimetic system to explore peptide and protein structure-function relationships. We now report the design and synthesis ofa small molecule (Mr 810, as its trifluoroacetate salt), water soluble, proteolyticaly stable mimetic of residues Gln4O-Thr45 of the complementarity-determining 2-like region of CD4. This mimetic has a low micromolar Kd for human T-lymphotropic virus type hUB gpl20 and reduces syncytium formation.

show abstract

Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication.

Cited by 22 publications

References 20 publications

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

An HIV gp120-CD4 Immunogen Does Not Elicit Autoimmune Antibody Responses in Cynomolgus Macaques

Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

Design and synthesis of a CD4 beta-turn mimetic that inhibits human immunodeficiency virus envelope glycoprotein gp120 binding and infection of human lymphocytes.

Contact Info

Product

Resources

About