Broadly Neutralizing Monoclonal Antibodies to the V3 Region of HIV-1 Can Be Elicited by Peptide Immunization

White‐Scharf, Mary E.; Potts, Barbara; Smith, Lloyd M.; Sokolowski, Karen A.; Rusche, James R.; Silver, Sandra

doi:10.1006/viro.1993.1022

Cited by 98 publications

(84 citation statements)

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“…This limits the variation of the elbow angles in the antibodies, with 142°f or R56 and 154°for R20. Some rabbit antibodies were predicted to have an alternative disulfide bond between residues 108 and 170 (20). Our structures showed that this is possible as the distance between the C-␣ atoms of these two residues is ϳ5.6 Å (Fig.…”

Section: Resultsmentioning

confidence: 79%

“…7A). Mouse MAb 50.1, although also produced by immunization, was induced by using the disulfide-linked 40-mer cyclic peptide RP70 (INCTRPNYNK RKRIHIGPGR AFYTTKNIIG TIRQAHCNIS), which contains the V3 sequence of strain MN of HIV-1 gp120 (20). The complex structure of MAb 50.1 was resolved to 2.8 Å resolution by cocrystallizing its Fab with another cyclic peptide, MP1 (CKRIHIGPGR AFYTTC) (27).…”

Section: Resultsmentioning

confidence: 99%

“…There are many anti-V3 MAbs derived from human patients, as well as from animal models other than the rabbit (20)(21)(22)(23)(24). Most of the known anti-V3 MAbs are against the V3 crown; only a few of them target the C-terminal region, including a mouse MAb raised by immunization with a synthetic peptide (25).…”

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confidence: 99%

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Rabbit Anti-HIV-1 Monoclonal Antibodies Raised by Immunization Can Mimic the Antigen-Binding Modes of Antibodies Derived from HIV-1-Infected Humans

Pan

Sampson

Chen

et al. 2013

J Virol

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The rabbit is a commonly used animal model in studying antibody responses in HIV/AIDS vaccine development. However, no rabbit monoclonal antibodies (MAbs) have been developed previously to study the epitope-specific antibody responses against HIV-1 envelope (Env) glycoproteins, and little is known about how the rabbit immune system can mimic the human immune system in eliciting such antibodies. Here we present structural analyses of two rabbit MAbs, R56 and R20, against the third variable region (V3) of HIV-1 gp120. R56 recognizes the well-studied immunogenic region in the V3 crown, while R20 targets a lessstudied region at the C terminus of V3. By comparison of the Fab/epitope complex structures of these two antibodies raised by immunization with that of the corresponding human antibodies derived from patients chronically infected with HIV-1, we found that rabbit antibodies can recognize immunogenic regions of gp120 and mimic the binding modes of human antibodies. This result can provide new insight into the use of the rabbit as an animal model in AIDS vaccine development.

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Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

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Rabbit Anti-HIV-1 Monoclonal Antibodies Raised by Immunization Can Mimic the Antigen-Binding Modes of Antibodies Derived from HIV-1-Infected Humans

Pan

Sampson

Chen

et al. 2013

J Virol

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“…The epitopes for, and some immunochemical properties of, anti-gp120 MAbs from various donors have been described previously (9,71,72). These include 19b and 83.1 to the V3 loop (74,118), IgG1b12 and F91 to the CD4 binding site (CD4bs) (15,72), 2G12 to a unique C3-V4 glycan-dependent epitope (108,109), M90 to the C1 region (113), 23A and sheep antibody D7324 to the C5 region (69,72), C11 to a discontinuous C1-C5 epitope (75), 17b to a CD4-inducible epitope (9,47,72,91,103,105,122,123), A32 to a CD4-inducible C1-C4 epitope (72,103), and G3-519 and G3-42 to C4 and C4/V3 epitopes, respectively (72,73). MAbs to gp41 epitopes included 7B2 to epitope cluster I (a gift from James Robinson); 4D4 to cluster I (11); T4, an oligomer-specific MAb overlapping the cluster I region (28); 2.2B to cluster II (a gift from James Robinson); T15G1 to cluster II (a gift from Ab Notkins); and 2F5 to a neutralizing epitope encompassing residues 653 to 659 (11,77,108).…”

Section: S]cysteine and [mentioning

confidence: 99%

A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure

Binley

Sanders²,

Clas

et al. 2000

J Virol

500

644

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The few antibodies that can potently neutralize human immunodeficiency virus type 1 (HIV-1) recognize the limited number of envelope glycoprotein epitopes exposed on infectious virions. These native envelope glycoprotein complexes comprise three gp120 subunits noncovalently and weakly associated with three gp41 moieties. The individual subunits induce neutralizing antibodies inefficiently but raise many nonneutralizing antibodies. Consequently, recombinant envelope glycoproteins do not elicit strong antiviral antibody responses, particularly against primary HIV-1 isolates. To try to develop recombinant proteins that are better antigenic mimics of the native envelope glycoprotein complex, we have introduced a disulfide bond between the C-terminal region of gp120 and the immunodominant segment of the gp41 ectodomain. The resulting gp140 protein is processed efficiently, producing a properly folded envelope glycoprotein complex. The association of gp120 with gp41 is now stabilized by the supplementary intermolecular disulfide bond, which forms with approximately 50% efficiency. The gp140 protein has antigenic properties which resemble those of the virionassociated complex. This type of gp140 protein may be worth evaluating for immunogenicity as a component of a multivalent HIV-1 vaccine.

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“…That a principal neutralization domain exists within the third hypervariable region of the envelope protein of HIV-1 and HIV-2 is well established (for review see Wolf et al, 1993) and there are data indicating that such regions consist of multiple and/or discontinuous epitopes (White-Scharf et al, 1993;Seligman, 1994;Bj6rling et al, 1994).…”

Section: S Lombardi and Othersmentioning

confidence: 99%

Epitope mapping of the V3 domain of feline immunodeficiency virus envelope glycoprotein by monoclonal antibodies

Lombardi

Massi²,

Tozzini³

et al. 1995

Journal of General Virology

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Broadly Neutralizing Monoclonal Antibodies to the V3 Region of HIV-1 Can Be Elicited by Peptide Immunization

Cited by 98 publications

References 0 publications

Rabbit Anti-HIV-1 Monoclonal Antibodies Raised by Immunization Can Mimic the Antigen-Binding Modes of Antibodies Derived from HIV-1-Infected Humans

Rabbit Anti-HIV-1 Monoclonal Antibodies Raised by Immunization Can Mimic the Antigen-Binding Modes of Antibodies Derived from HIV-1-Infected Humans

A Recombinant Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Complex Stabilized by an Intermolecular Disulfide Bond between the gp120 and gp41 Subunits Is an Antigenic Mimic of the Trimeric Virion-Associated Structure

Epitope mapping of the V3 domain of feline immunodeficiency virus envelope glycoprotein by monoclonal antibodies

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