Background/problem
Coronaviruses, including SARS-CoV-2, caused the COVID-19 pandemic of plague-like infectiousness with >770 M cases and 6.9M deaths worldwide. Vaccination provided protection against severe disease progression, hospitalization, and mortality. However, current vaccine technology is in an arms race against the continual evolution and emergence of several SARS-CoV-2 variants of concern (VOCs). Some vaccines, while effective, generally induce one’s immunity towards the hypervariable S1 domain of the spike protein of the virus. This approach renders them ineffective against VOCs that predictably harbors multiple mutations within S1 and resist neutralizing antibodies targeting this domain. In contrast, the stem domain of spike (S2) is more conserved and targeted by several broadly cross-reactive human monoclonal antibodies. Thus, it is a viable target, with S2 antigen possibly eliciting broadly protective antibodies for immunity. However, S2 structure is metastable and needed a structural conformation that will elicit the efficient, broad-spectrum immunogenic response.
Tech overview/solution
UT Austin’s McLellan Group, inventors of the S1-stabilized protein of many leading COVID-19 vaccines, identified key amino acid mutations that enhanced thermostability and cellular expression of the closed-form S2-only antigen. Together with the country’s leaders of vaccine technology design, they devised a self-assembling insect ferritin nanoparticle (NP) platform that displays the S2-stabilized antigen on its surface. Presenting the antigens on bioengineered particles that mimic the geometric patterns observed for native viral proteins, facilitates B cell activation and leads to an improved host-antibody response. This S2-NP technology elicited cross-reactive antibody responses to SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV OC43, HCoV, and endemic human coronaviruses HKU1 and OC43.
Benefits/competitive advantage
- Broad immune response: Elicits cross-reactive and neutralizing antibodies
- Targeted protection: Specifically targets the conserved S2-stabilized antigen
- Variant-proof design: Designed to provide immunity against new variants
- Pan-Coronavirus approach: Offers potential protection against a wide range of coronaviruses
- Futureproofing: Provides immunity for both current and future pandemics
Opportunity
The severity of COVID-19 infection has decreased, but infection persists. With viruses undergoing mutations to spread new VOCs, effective vaccines are still needed, especially to aid vulnerable populations. The largest market for vaccines is for COVID-19, expected to reach a value of $108B through 2027. Growth for COVID-19 vaccine market can be attributed to expected inclusion of vaccines in the routine immunization programs (with CDC adding COVID-19 into routine immunization list), vaccination programs in less-developed countries, and strong vaccine pipeline where S2-NP technology can be a driving force. In addition, the S2-NP technology can also be used as a research reagent to isolate specific S2-directed antibodies. For parties/companies with interest in therapeutics, vaccine technology, coronavirus research.
