Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptides

Dreesman, Gordon R.; Sanchez, Yanuario; Ionescu-Matiu, Irina; Sparrow, James T.; Six, Howard R.; Peterson, Darrell L.; Hollinger, F. Blaine; Melnick, Joseph L.

doi:10.1038/295158a0

Cited by 194 publications

(66 citation statements)

References 19 publications

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“…Liposome-based formulations were prepared following the methods described by Dreesman et al (60) and Maeso et al (61) and included lipid A as adjuvant (62). MPERp in DMSO was added at a final peptide-to-lipid ratio of 1:50 (mol/mol) to a stirring solution of freeze-thaw POPC/Chol/PA/lipid A (2.0:1.5:0.2:0.01 molar ratio) or POPG/ lipid A (3.7:0.01 molar ratio) vesicles dispersed in PBS.…”

Section: Methodsmentioning

confidence: 99%

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Serrano

Araujo

Apellániz

et al. 2014

Journal of Biological Chemistry

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Background: HIV-1 vaccines should elicit broadly neutralizing antibodies as the gp41 "membrane-proximal external region" targeting MAb2F5. Results: NMR disclosed unprecedented 2F5 peptide-epitope structures. Although overall conformation was preserved in different adjuvants, recovered antibodies after vaccination were functionally different. Conclusion: Membrane-inserted helical oligomers may encompass effective 2F5 peptide vaccines. Significance: Disclosing the structures that generate 2F5-like antibodies may guide future vaccine development.

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Section: Methodsmentioning

confidence: 99%

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Serrano

Araujo

Apellániz

et al. 2014

Journal of Biological Chemistry

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“…H uman hepatitis B virus (HBV) is a small enveloped DNA virus that causes acute and chronic hepatitis in humans (1)(2)(3). There are approximately 400 million carriers of HBV worldwide, posing a serious health threat.…”

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confidence: 99%

Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism

Chi

Maeng²,

Kim

et al. 2007

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

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The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the human hepatitis B virus surface proteins with a broadly neutralizing activity in vivo. We present the crystal structures of HzKR127 Fab and its complex with a major epitope peptide. In the complex structure, the bound peptide forms a type IV ␤-turn followed by 310 helical turn, the looped-out conformation of which provides a structural basis for broad neutralization. Upon peptide binding, the antibody undergoes a dramatic complementarity determining region H3 lid opening. To understand the structural implication of the virus neutralization, we carried out comprehensive alanine-scanning mutagenesis of all complementarity determining region residues in HzKR127 Fab. The functional mapping of the antigen-combining site demonstrates the specific roles of major binding determinants in antigen binding, contributing to the rational design for maximal humanization and affinity maturation of the antibody.alanine-scanning mutagenesis ͉ crystal structure ͉ humanized antibody ͉ virus neutralization H uman hepatitis B virus (HBV) is a small enveloped DNA virus that causes acute and chronic hepatitis in humans (1-3). There are approximately 400 million carriers of HBV worldwide, posing a serious health threat. The current HBV vaccines have several limitations, including nonresponsiveness, escape mutants, and low immunogenicity (4). Recently, the potential of immunoprophylaxis for virus prevention has been increased by the discovery of monoclonal antibodies that have broad specificity toward various isolates of infectious viruses (5, 6).The HBV envelope consists of three surface glycoproteins called the large (L), middle (M), and small (S) proteins. All of these proteins are translated from a single ORF comprising preS1, preS2, and S domains (7). Translation of S, preS2ϩS, and preS1ϩpreS2ϩS domains results in S, M, and L proteins, respectively (Fig. 1). The L protein, preferentially localized in infectious HBV particles, plays an essential role in viral infection (7,8), and its preS1 domain is responsible for cell attachment in viral infection (9-12). In particular, the residue 21-47 region of preS1 has been suggested to contain a specific binding site for hepatocyte receptors and also has been shown to carry virusneutralizing epitopes (10-13).In the blood of HBV-infected persons, the noninfectious subviral particles with M and S proteins are present in excess amounts over the infectious virus particles containing L protein (7,8). Thus, neutralizing anti-preS1 antibodies are thought to have advantages over the neutralizing antibodies targeting S protein, which are currently undergoing clinical trials (4). Previously, we generated an anti-preS1 murine antibody KR127 that recognizes adr subtype preS1 (residues 37-45) (15). KR127 and the humanized version of KR127 antibody (HzKR127) bind to the preS1 domain of various clinical HBV isolates, including both adr and ayw subtypes, suggesting their broad neutralizing activity (15, 16). HzKR127 also has been sh...

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“…The latter might be the situation with the influenza hemagglutinin loop. For such a rigid antigenic site, peptides with fixed conformation may be the more potent immunogens [26].…”

Section: Discussionmentioning

confidence: 99%

“…To ensure the described loop structure the ends of the synthetic peptides were covalently linked by a disulfide bridge. Dreesman et al [26] have described a similar approach for raising antibodies to hepatitis B surface antigen. The disulphide bond was placed in a position which should not have any influence on the sequence-inherent information for the three-dimensional structure of the loop region.…”

Section: Peptide Designmentioning

confidence: 99%

“…In order to evaluate the relevance of the three-dimensional structure we decided to design a peptide which carries the relevant sequence 140-146 inserted into a skeleton, thereby forcing it into a loop structure. The latter was approached by synthesizing cyclic peptides containing disulphide bonds since disulphide cycliza- tion is expected to result in a potent immunogen by locking the secondary structure [26]. We show that antibodies, raised against this loop peptide, are mainly directed towards the loop region and that they react with the native virus, although the binding to the virus is much weaker and less specific than to the respective immunogenic peptide.…”

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confidence: 99%

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Immunogenicity of loop-structured short synthetic peptides mimicking the antigenic site A of influenza virus hemagglutinin

Schulze‐Gahmen¹,

Klenk

Beyreuther³

1986

Eur J Biochem

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In order to assess the relevance of conformation for the antigenic site A of the hemagglutinin of influenza virus we synthesized two peptides, comprising two variant sequenes of the central part of site A (amino acids 140–146 of subunit HA1) inserted into an artificial peptide skeleton, which imposes a loop‐like structure on the respective sequence stretch. Assuming that the loop structure in the synthetic peptides would roughly approximate to the structure of the cognate protein sequence we tried to raise protein‐reactive anti‐peptide antibodies. The antibodies obtained indeed showed reactivity against influenza virus, although the discriminating specificity with regard to a mutation at position 144 was lost for virus binding in contrast to the highly specific peptide binding. Considering the failures in raising anti‐hemagglutinin antibodies against the site A by immunization with short flexible peptide our results support the hypothesis that conformation makes a major contribution to the immunogenic and antigenic characteristics of site A in influenza hemagglutinin.

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Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HBsAg peptides

Cited by 194 publications

References 19 publications

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism

Immunogenicity of loop-structured short synthetic peptides mimicking the antigenic site A of influenza virus hemagglutinin

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