BACKGROUND
The development of effective vaccines against HCV has been challenging due to the virus's high genetic variability, which allows it to evade immune responses. Traditional vaccine approaches have focused on conserved elements of the virus, aiming to elicit broad immune responses. However, these strategies have seen limited success, as the virus's ability to rapidly mutate and adapt has thwarted efforts to create a universally effective vaccine. Researchers are now exploring novel approaches, such as targeting conserved residues within highly variable regions of the virus, to overcome these obstacles and develop vaccines that can provide broad, cross-genotypic protection against HCV and other viruses.
TECHNOLOGY
Our researcher had developed an innovative HCV vaccine incorporating the 20 C-terminal amino acids of HVR1, conjugated to Keyhole limpet hemocyanin (KLH). This design preferentially elicits antibodies to the C-terminus of HVR1, a neutralizing epitope under greater negative selection than the N-terminus. This vaccine was develop using a novel measure of antigenic similarity, termed Mahalanobis Hamming Distance (MIH), to select HVR1 sequences for the polyvalent formulation. MIH weighs amino acid differences by considering the variability of each position (Shannon entropy) and the coordination between pairs of positions (mutual information). This approach constructs a k-step network of HVR1 sequence space, identifying central variants for synthesis and immunization.
COMPETITIVE ADVANTAGE
- Targeted Immunogen Design: Focuses on conserved C-terminal residues of HVR1, enhancing the likelihood of eliciting neutralizing antibodies.
- Novel Antigenic Similarity Measure: MIH provides a sophisticated method for selecting HVR1 sequences, improving vaccine efficacy.
- Broad Neutralizing Response: Demonstrated ability to elicit cross-genotypic neutralizing antibodies, addressing the challenge of viral variability.
APPLICATIONS
- HCV Vaccine: Provides a promising solution to the challenge of genetic diversity in HCV, potentially overcoming obstacles faced by previous vaccine efforts.
- Viral Vaccine Research: Offers insights and methodologies applicable to vaccine development for other highly variable viruses, such as HIV.
INTELLECTUAL PROPERTY STATUS
- National Phase: CA, EU, US (Nov 2022)
PROJECT STATUS
Proof-of-concept studies have been conducted. The vaccine candidate has been validated through mouse immunizations, demonstrating broad, cross-genotypic neutralizing antibodies.
KEYWORDS
HCV vaccine, HVR1, conserved residues, antigenic similarity, MIH, polyvalent formulation, neutralizing antibodies, viral variability.
