Electrophilic Vaccines (E-Vaccines) Platform for HIV
Equipped with a team of professional scientists, Creative Biolabs has developed a method to stimulate B cells by covalently binding an immunogen containing a strong electrophilic phosphonate group to the native nucleophilic site of antibodies. Our electrophilic vaccines against HIV which contain electrophilic polypeptides bind covalently to B cells, resulting in widely neutralized antibodies. In addition to the HIV E-vaccine, our platform is ready to help our customers develop derivatives that can be applied to other diseases that are still difficult to solve with traditional vaccinations.
Strategies of Using Electrophilic Immunogens (E-immunogens) to Stimulate B-cell
Creative Biolabs has developed a method to stimulate B cells by covalently binding an immunogen containing a strong electrophilic phosphonate group to the native nucleophilic site of antibodies. These sites were originally identified in the enzyme of the serine protease family as a triplet of Ser(Thr)-His-Asp(Glu) residues. The serine/threonine side chain oxygen provides enhanced nucleophilic reactivity due to intramolecular hydrogen bonding, thereby enabling formation of covalent intermediates with the weak electrophilic carbonyl groups of the polypeptide substrate. We prepared covalently reactive immunogens by introducing an electrophilic phosphonate group on the amino acid side chain of the polypeptide. The specific non-covalent association of the electrophile in this immunogen with the peptide epitope synergistically shows covalent binding to the nucleophilic signal-transducing proteins (BCRs).
E-immunogens gp120 as Candidate Vaccines for HIV
E-immunogens, which are vaccine candidates for microbial vaccines, use superepitope epitopes to bind to immunoglobulin framework regions (FRs) expressed as B cell receptors (BCR), thereby inhibiting the adaptive antibody response needed for protection against infection. The envelope protein gp120 is an important component of the HIV life cycle and is the main target of vaccine development. Unlike gp120, the electrophilic gp120 analog (E-gp120) forms covalent oligomers. Epitope mapping with synthetic peptides and electrophile analogs indicated that the anti-E-gp120 mAb recognizes two distinct gp120 regions, namely the 421-433 (CLIN) and 288-306 peptide regions, respectively. The superantigen gp120 residues 421-433 (CLIN) bind to the CD4 receptor and are important for the establishment of HIV-1 infection. Consistent with the designation of CLIN as a superantigen, uninfected humans innately produce IgM + BCRs and secreted IgM with FRs that recognizes CLIN and catalyzes the degradation of gp120 monomer. However, only the CLIN-directed variable (V) domain of IgGs / IgAs, rather than IgMs, binds to intact HIV and neutralized genetically diverse HIV strains, suggesting that IgM→IgG/IgA-like conversion (CS) is a prerequisite for effective HIV vaccination.
Fig.1 Structural aspects of CD4 binding site 421-433 epitope recognition by antibodies. (A) Split-site model explaining proteolytic Ab epitope specificity. (B) Surface model of anti-E-glycoprotein 120 Fab YZ23 crystal solved at 2.5 Å resolution (PDB 3CLE). (Paul S. 2010)
E-Vaccines Platform for HIV
Creative Biolabs is dedicated to the development of Electrophilic Vaccines against HIV which contains electrophilic polypeptides and binds covalently to B cells, resulting in widely neutralized antibodies. The polypeptide is chemically activated by attaching a lysine side chain to a strong electrophilic phosphonate diester group. Naturally occurring nucleophilic sites are commonly found in B cell receptors. The non-covalent attachment of the peptide epitope to the B cell receptor places the electrophilic group within the covalent binding distance of the nucleophilic group. Subsequent covalent bonds between the electrophile and the nucleophile release a large amount of energy that triggers productive signal transduction, IgM→IgG/IgA antibody class switching, and cell differentiation into antibody-secreting plasma cells.
E-Vaccine Platfrom Expansion
In addition to the HIV E-vaccine, Creative Biolabs’ platform is ready to develop derivatives that can be easily applied to many other diseases that are still difficult to solve with traditional vaccinations, such as:
- Infectious disease: Staphylococcus aureus, Hepatitis C virus, and other virus that evades human immunity through a mechanism similar to HIV.
- Cancer
- Autoimmune disease
- Allergic Diseases
If you are interested in our services, please contact us to get more information or directly send us an online inquiry.
Reference
- Paul S, et al. Back to the future: covalent epitope-based HIV vaccine development. Expert Rev Vaccines. 2010, 9(9):1027-43.
All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.
