Description:
 
Background
Current vaccines rely upon the host to develop a high-affinity antibody response that binds to neutralize epitopes of a pathogen. Pathogens that can easily mutate, influenza or HIV for example, can quickly evade the immune response elicited by the vaccine. Researchers have identified that a fraction of patients with chronic HIV infection has been able to develop so-called broadly-neutralizing antibodies (bnAb) that specifically bind to these highly conserved regions of HIV. These antibodies have been shown to prevent infection from over 70% of known HIV strains and are highly protective. 
However, the major problem in eliciting the desired bnAb is that these epitopes are weakly immunogenic and are not efficient at activating cognate B cells. 
During the humoral immune response, only a limited level of survival and propagation signals are available. As a result, B cells that are specific towards these broadly-neutralizing epitopes are outcompeted by immunodominant, non-broadly-neutralizing B cell clones.
 
Technology Overview
Researchers at Northeastern University have developed a method in which a mutated soluble antigen without adjuvant is administered during an ongoing immune response in order to specifically eliminate the immunodominant B cell response. This process allows subdominant B cells to acquire necessary survival signals and expand.
In a related method, inhibitory signaling molecules that prevent B cell into GC B cells, plasma cells, or memory B cells (bcl-6 inhibitor, mTor inhibitor, akt inhibitor) are conjugated directly to the mutated immunogen or loaded into a liposomal delivery system, where the mutated immunogen is displayed on the surface of the liposome. This method can be used to prevent irrelevant B cells from being activated. In some cases, the inhibitory molecule can be replaced for a cytotoxic/chemotherapeutic molecule.
The invention of these methods and compositions can eliminate the immunodominant non-broadly-neutralizing immune response. This technology enables preferential expansion of subdominant B cells that target specific epitopes of interest and may be applied to generate broadly neutralizing vaccines against elusive pathogens, such as Influenza and HIV.
 
Benefits
- Can be used to target desired epitopes
- Allows for a rational epitope targeting strategy that significantly reduces screening time
- Can qualitatively alter the specificity of the immune response
 
Applications
- Any vaccination regime 
- Biomedical or research use
 
Opportunity
- License
- Partnering
- Research Collaboration
Patent Information:
Category(s):
Biotechnology
For Information, Contact:
Mark Saulich
Associate Director of Commercialization
Northeastern University
m.saulich@northeastern.edu
Inventors:
Murillo Silva
Michail Sitkovsky
Keywords: