Stamatatos Vaccine Discovery Consortium
OVERVIEW:
The Stamatatos-led VDC takes advantage of the latest advances made in various areas, including immunology, virology, molecular biology and computational-based design methodologies, to develop novel strategies to design an anti-HIV vaccine. Investigators with diverse but complementary backgrounds participate in the consortium. In particular, the research are working to develop a vaccine that would elicit antibodies capable of preventing infection by multiple HIV-1 strains.
One promising target of these antibodies is an epitope located near the transmembrane subunit of envelope protein gp41. Previous work by others has shown that the broadly neutralizing antibody 4E10 binds to this epitope, which is located in a region of the viral envelope, called the membrane proximal external region (MPER). The 4e10 epitope is relatively highly conserved across the strains of HIV-1 and is involved in HIV’s fusion with host cells.
RESEARCH OBJECTIVES:
- Evaluate the ability of computationally designed immunogens to elicit anti-HIV neutralizing antibodies;
- Engineer and evaluate the immunogenic properties of novel trimeric gp140 HIV envelope proteins composed of non-identical gp140 protomers (gp140 heterotrimers);
- Define the crystal structure of immunogens, coupled or not to their natural or artificial ligands; and
- Isolate and characterize broadly reactive NAbs from SHIV-infected non-human primates that display broad serum neutralizing activity.
PROGRESS:
The Stamatatos VDC performed over 50 immunization studies in animals with novel immunogens and analyzed the elicited antibody responses. The researchers also recently obtained results that indicate that their computationally-designed immunogens, mixed with appropriate adjuvants, elicit antibodies with the appropriate binding specificities against conserved HIV-1 neutralization epitopes
Researchers with the Stamatatos-led VDC obtained and analyzed crystal structures of several of their immunogens and this structural information, combined with their vaccine data, allow them to optimize their vaccine-design efforts.