Chimeric hepatitis E virus-like particle as a carrier for oral-delivery.

Oral delivery with virus-like particles (VLPs) is advantageous because of the inherited entry pathway from their parental viral capsids, which enables VLP to withstand the harsh and enzymatic environment associated with human digestive tract. However, the repeat use of this system is challenged by the self-immunity. In order to overcome this problem, we engineered the recombinant capsid protein of hepatitis E virus by inserting p18 peptide, derived from the V3 loop of HIV-1 gp120, into the antibody-binding site.

Developing strategies to enhance and focus humoral immune responses using filamentous phage as a model antigen.

Filamentous bacteriophage are commonly used as immunogenic carriers for peptides and proteins displayed on the phage surface. Previously, we showed that immunization with phage to which peptides had been chemically conjugated can elicit a focused anti-peptide antibody response compared with traditional carrier molecules bearing the same peptide, perhaps due to the low surface complexity of the phage. The regularity of its surface also gives the phage other advantages as a carrier, including immunological simplicity and thousands of well-defined sites for chemical conjugation.

Engineering filamentous phage carriers to improve focusing of antibody responses against peptides.

The filamentous bacteriophage are highly immunogenic particles that can be used as carrier proteins for peptides and presumably other haptens and antigens. Our previous work demonstrated that the antibody response was better focused against a synthetic peptide if it was conjugated to phage as compared to the classical carrier, ovalbumin. We speculated that this was due, in part, to the relatively low surface complexity of the phage.

Exploring peptide mimics for the production of antibodies against discontinuous protein epitopes.

Peptide "mimics" (mimotopes) of linear protein epitopes and carbohydrate epitopes have been successfully used as immunogens to elicit cross-reactive antibodies against their cognate epitopes; however, immunogenic mimicry has been difficult to achieve for discontinuous protein epitopes. To explore this, we developed from phage-displayed peptide libraries optimized peptide mimics for three well-characterized discontinuous epitopes on hen egg lysozyme and horse cytochrome c. The peptides competed with their cognate antigens for antibody binding, displayed affinities in the nM range, and shared critical binding residues with their native epitopes.

The membrane-proximal external region of the human immunodeficiency virus type 1 envelope: dominant site of antibody neutralization and target for vaccine design.

Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens.

Structure of a high-affinity "mimotope" peptide bound to HIV-1-neutralizing antibody b12 explains its inability to elicit gp120 cross-reactive antibodies.

The human antibody b12 recognizes a discontinuous epitope on gp120 and is one of the rare monoclonal antibodies that neutralize a broad range of primary human immunodeficiency virus type 1 (HIV-1) isolates. We previously reported the isolation of B2.1, a dimeric peptide that binds with high specificity to b12 and competes with gp120 for b12 antibody binding.