HIV-1 V3 loop crown epitope-focused mimotope selection by patient serum from random phage display libraries: implications for the epitope structural features.

The crown region of the V3 loop in HIV-1 that contains the conserved amino acid sequence GPGR/G is known as the principal neutralizing determinant due to the extraordinary ability of antibodies to this region to neutralize the virus. To complement the existing peptide models of this epitope, we describe a family of 18 phage-displayed peptides, which include linear 12mer and constrained 7mer peptides that was selected by screening random libraries with serum from HIV-1 subtype B-infected patients. The 7mer constrained peptides presented two conserved amino acid sequences: PR-L in N-terminus and GPG in the C-terminus.

Mimotope peptides selected from phage display combinatorial library by serum antibodies of pigs experimentally infected with Taenia solium as leads to developing diagnostic antigens for human neurocysticercosis.

Neurocysticercosis is caused by penetration of the tapeworm Taenia solium larvae into the central nervous system resulting in a diverse range of neurologic complications including epilepsy in endemic areas that globalization spreads worldwide. Sensitive and specific immunodiagnosis is needed for the early detection and elimination of the parasite, but the lack of standardized, readily obtainable antigens is a challenge. Here, we used the phage display for resolving the problem.

Synthetic peptide-targeted selection of phage display mimotopes highlights immunogenic features of α-helical vs non-helical epitopes of Taenia solium paramyosin: implications for parasite- and host-protective roles of the protein.

Paramyosin of the pig-human parasite Taenia solium (TPmy) is a α-helical protein located on the worm surface that is suggested to fulfill an immunomodulatory role protecting the parasite against host immune system. Besides, in challenging experiments the protein shows a vaccine potential. These observations imply that TPmy harbors antigenic determinants for each of these contrasting actions.

Phage display identifies two Caprine Arthritis Encephalitis Virus env epitopes.

Using phage display and IgG of a goat infected with Caprine Arthritis Encephalitis Virus (CAEV) we obtained families of 7 mer constrained peptides with consensus motifs LxSDPF/Y and SWN/KHWSY and mapped the epitopes mimicked by them at the Env 6-LISDPY-11 and 67-WNTYHW-72 sites of the mature gp135 amino acid sequence. The first epitope fell into the N-terminal immunogenic aa1-EDYTLISDPYGFS- aa14 site identified previously with a synthetic peptide approach; the second epitope has not been described previously. The first epitope is mostly conserved across CAEV isolates whereas the second newly described epitope is extremely conserved in Small Ruminant Lentiviruses env sequences.

Immunogenic peptides from phage display libraries with potential of protecting mice against the Pseudorabies virus.

Phage display selection of combinatorial peptide libraries has demonstrated its almost unlimited potential in identifying binding ligands for many targets. The method shows promise for selection of immunogenic peptides against pathogens by antibodies. We have undertaken a study designed to select such mimics for one of the representatives of Herpesviridae, the Pseudorabies virus (PrV), infecting pigs and causing severe neurological complications known as Aujeszky's disease.

Constrained peptide models from phage display libraries highlighting the cognate epitope-specific potential of the anti-HIV-1 mAb 2F5.

The monoclonal antibody 2F5 (mAb 2F5), one of the most potent broadly neutralizing mAbs targeted to the HIV-1 gp41 membrane proximal exterior region (MPER), displays an unusually wide antigenic specificity, tolerating amino acid substitutions at virtually all positions of the 662-ELDKWAS-668 epitope sequence when presented by peptides. Investigating this phenomenon, Menendez et al. [22] concluded that the paratope of 2F5 contains two distinct binding compartments.

Peptide sequences identified by phage display are immunodominant functional motifs of Pet and Pic serine proteases secreted by Escherichia coli and Shigella flexneri.

Plasmid-encoded toxin (Pet) and protein involved in colonization (Pic), are serine protease autotransporters of Enterobacteriaceae (SPATEs) secreted by enteroaggregative Escherichia coli (EAEC), which display the GDSGSG sequence or the serine motif. Our research was directed to localize functional sites in both proteins using the phage display method. From a 12mer linear and a 7mer cysteine-constrained (C7C) libraries displayed on the M13 phage pIII protein we selected different mimotopes using IgG purified from sera of children naturally infected with EAEC producing Pet and Pic proteins, and anti-Pet and anti-Pic IgG purified from rabbits immunized with each one of these proteins.

Collection of phage-peptide probes for HIV-1 immunodominant loop-epitope.

Early diagnosis and prevention of human immunodeficiency virus type-1 (HIV-1) infection, which remains a serious public health threat, is inhibited by the lack of reagents that elicit antiviral responses in the immune system. To create mimotopes (peptide models of epitopes) of the most immunodominant epitope, CSGKLIC, that occurs as a loop on the envelope gp41 glycoprotein and is a key participant in infection, we used phage-display technology involving biopanning of large random libraries with IgG of HIV-1-infected patients. Under the conditions used, library screening with IgG from patient serum was directed to the CSGKLIC epitope.

Immunology of scorpion toxins and perspectives for generation of anti-venom vaccines.

Scorpions and other venomous animals contain concentrates of biologically active substances developed to block vital physiological and biochemical functions of the victims. These have contrasting human health concerns, provide important pharmacological raw material and pose a serious threat to human life and health in tropical and subtropical regions. Because only occasional and minor quantities of venom are introduced into the human organism with a scorpion sting and their mortal effect is an acute phenomenon these substances are unknown to the immune defense system and thus no immunity has appeared against them during evolution.

Potential of peptides selected from random phage-displayed libraries to mimic conformational epitopes: a study on scorpion toxin Cn2 and the neutralizing monoclonal antibody BCF2.

Many conformational epitopes cannot be mapped by the use of a phage display approach due to the lack of amino acid similarity with the selected peptides. Exploring the potential of the method, we selected mimotopes of the discontinuous, highly conformational epitope of scorpion neurotoxin Cn2, whose 3D structure is known, using its generic neutralizing monoclonal antibody BCF2. With an exhaustive selection procedure, we isolated from a 12-mer phage library a large collection of mimotopes that reproduce the antigenic and immunogenic specificity of the Cn2-epitope.

Molecular localization and crossreactivity of two epitopes of noxiustoxin from scorpion Centruroides noxius, identified by a panel of monoclonal antibodies and peptide mimotopes.

Mimotopes derived from peptide phage display libraries may reproduce basic functions of epitopes including their antigenicity. In case of toxins, this property makes phage displayed mimotopes highly specific vaccine components free of the toxicity. To explore the potential of mimotopes for vaccine development, their ability of substituting the whole toxin molecule deserves a detailed characterization.