Pan-betacoronavirus Neutralizing Antibodies
Through Cure-Hub's independent COVID-19 antibody survey, I collected a few hundred serum samples. These were tested for neutralizing antibodies against the SARS-CoV-2 receptor binding domain (RBD). The RBD is important because it is responsible for viral binding to human cells, and is the viral region targeted by vaccines. Now it is apparent the RBD can undergo quick mutation, which leads to immune escape and breakthrough or repeat infections. Recent data shows there is a different region of the virus, called S2 which has specific areas that are conserved across most betacoronaviruses. Furthermore, some antibodies bind this conserved S2 region, and those antibodies have been shown to neutralize SARS-2, SARS-1, MERS and common cold coronaviruses. These antibodies are thought to be more common in people who have had a natural infection. Due to a phenomenon known as Original Antigenic Sin, formation of those pan-betacoronavirus antibodies may be inhibited in people who have received a vaccine. For this project I seek to test the samples I have already acquired. Samples will be tested for antibodies against the SARS-CoV-2 S2 domain, S1 domain (where the RBD is located) as well as the nucleocapsid protein. This preliminary data should indicates the likelihood of formation of pan-betacoronavirus antibodies. This would be important for considerations related to updating vaccines, and potential for long term protection against multiple betacoronaviruses. If those tests go as planned, we will know if S2 antibodies are present in people with natural immunity, and if they form in people who were vaccinated. Keep in mind testing for the presence of S2 antibodies is not enough to know if the pan-betacoronavirus antibodies did form. To know that we will need to add another project where we look at antibodies to the specific regions of the S2 domain. It is my opinion this project would be unique and informative to our understanding of immune memory, viral escape and the capacity of our immune system to redirect its response with various types of exposures.
Cure-Hub performed one of the only nationwide COVID19 antibody surveys in the nation. This project was an independent, citizen science endeavor. Participants signed an informed consent, then paid for their test. They were then sent a home sample collection kit and they then sent their sample to the Cure-Hub lab. They received their neutralizing antibody test results, then deidentified data was posted on open access data visualizations at Cure-Hub.com. The study is now closed to new participants but the samples can still be tested for other purposes. Now I would like to test those samples to better understand dynamics of the immune response based on vaccination and/or natural infections. To do this we need to test antibodies in the samples against new viral regions.
Samples from these cohorts will be tested against for antibodies against the SARS-CoV-2 S1, S2 domains and nucleocapsid protein: Pfizer mRNA vaccine x2 Moderna mRNA vaccine x2 J&J vaccine Pfizer/Moderna mRNA vaccine x3 Natural Infection only mRNA vaccine -> natural infection natural infection -> mRNA vaccine negative controls
SARS-CoV-2 S1 and S2 domains, and nucleocapsid antibody testsRequired Funding$15,000
Existing samples will be tested via ELISA. Funding will pay for the purchase of the tests, which are commercially available.