A pandemic has been ravaging the world for two years now. Millions of lives have been lost to this severe acute respiratory syndrome coronavirus (SARS-CoV-2) and yet world leaders are at loss for the correct actions to take. Thankfully, a majority of individuals only experience mild symptoms and do not require hospitalization[1]. Increased knowledge and access to usable and current data is critical to monitoring the situation as the virus mutates and more variants are discovered. We are proposing to collect and assess data from individuals around the globe. This volunteer based scientific study is composed of two parts:
- A blood assessment to monitor current immune response in whole blood when exposed to SARS-CoV-2
- A collection of data from survey of questions
The number of individuals capable of producing a specific immune response when exposed to SARS-CoV-2 is still unknown. Studies demonstrate individuals develop SARS-CoV-2 specific memory B cells, memory T cells, IgG antibodies, and neutralizing plasma for at least three months after recovery[2]. Yet a comprehensive assessment of a populations current immune response has yet to be completed. We know of no reason why data on individuals whole blood assessing their current ability to respond to exposure to SARS-CoV-2 is not being collected.
The U.S. Department of Health & Human Service (HHS) lists the Nuremberg Code: Directives for Human Experimentation on it’s website[3]. This includes:
- “The voluntary consent of the human subject is absolutely essential” Therefore, prior to any medical procedure the consent of the human subject is absolutely essential.
- “The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease.” Without having prior knowledge of the history of the SARS-CoV-2 virus and how it affects the individual immune systems,initial experiments should have included a worldwide data collection of outcomes of the disease correlated to medications patients were taking prior to a Covid-19 infection as well as their health history.
- “The experiment should be conducted as to avoid all unnecessary physical and mental suffering and injury.” Since assessment of individual immune responses to viruses is required in order to design and develop vaccines, immunity assessment should have been made available to the public prior to authorizing the emergency use of SARS-CoV-2 vaccines.
The FDA explains Emergency Use Authorization and the requirements including[4]: “Initially, in phase 1, the vaccine is given to a small number of generally healthy people to assess its safety at increasing doses and to gain early information about how well the vaccine works to induce an immune response in people.” This proves the FDA required immune response data at Phase 1, PRIOR to giving a EUA to the vaccines. Phase 2 studies “provide additional safety information on common short-term side effects and risks, examine the relationship between the dose administered and the immune response.” Phase 3 provides additional information about the immune response in people who received the vaccine compared to those who received a control, such as a placebo. The fact the FDA had to evaluate “immune response data,” means the FDA is aware immunity assessment is available. The fact the FDA did not first require immunity assessment for every participant prior to any EUA vaccinations is a travesty and goes against the Nuremberg code. The vaccines should only have been administered to those who did not demonstrate a current immune response. Pre-vaccination immunity assessment will target at risk individuals, allowing for faster vaccine distribution, and decreasing unnecessary vaccinations.
Immunity assessment is far from novel and numerous techniques can be utilized including protein/protein interactions[5], cell population response[6], antibody release[7]. A 1977 study on antibody-forming cells differentiating to antigen-specific (memory) B cells, demonstrates our scientific ability 45 years ago to monitor the types and prevalence of antibodies (IgG, IgA, IgM, IgD expressed on the surface of immune cells[8]. Yet somehow, immunity assessment prior to vaccination is not readily available during a pandemic?
A novel assay relying on integrin activation demonstrates the ability to monitor ex vivo effector cells for SARS-CoV-2, cytomegalovirus, Hepatitis B virus, and Epstein-Barr virus in whole blood or peripheral blood immune cells known as mononuclear cells (PBMCs) of vaccinated of previously infected individuals[9].
From the beginning of the pandemic epidemiologists have stressed the importance of immune based assays to determine previous exposure to SARS-CoV-2[10]. Within the first weeks of the pandemic it was determined the receptor binding domain (RBD) portion of the SARS-CoV-2 spike protein bound strongly to both bat and human angiotensin-converting enzyme 2 receptors (ACE2)[11].
Our ImmunoCure foundation’s immunity assessment protocol utilizes GenScript’s cPass neutralizing antibody ELISA assay [5, 12]. Whole blood from volunteers is inoculated with tagged SARS-CoV-2 spike proteins and allowed to incubate at 37C. After incubation the immune cells, red blood cells, and platelets are spun out of the sample and the remaining plasma is tested. Our protocol assesses the difference between whole blood inoculated with a tagged SARS-CoV-2 prior and after (control) incubation. If the individual’s whole blood is stimulated to release neutralizing antibodies within hours of exposure to SARS-CoV-2, this a positive immune response. We feel this information along with the subject questionnaire information will provide valuable information to the public. Our databank will provide one definite place for individuals to go for an up to date comprehensive understanding of the pandemic crisis. Go to www.immunityassessment.com to find out how you can become involved in making a difference.
- Zunyou Wu, J.M.M., Characterisitics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA, 2020. 323(13): p. 1239-1242.
- Rodda, L.B., et al., Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19. Cell, 2021. 184(1): p. 169-183.e17.
- Code, N.
- FDA.
- Tan, C.W., et al., A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2–spike protein–protein interaction. Nature Biotechnology, 2020. 38(9): p. 1073-1078.
- Son, Y.M., et al., Tissue-resident CD4+ T helper cells assist the development of protective respiratory B and CD8+ T cell memory responses. Science Immunology, 2021. 6(55).
- Ma, Z., et al., Toward a Functional Cure for Hepatitis B: The Rationale and Challenges for Therapeutic Targeting of the B Cell Immune Response. Frontiers in Immunology, 2019. 10.
- Sameul J Black, W.V.D.L., Michael R Loken, Leonard A Herzenberg, Expression of IgD by Murine Lymphocytes. J Exp Med, 1977: p. 984-996.
- Schöllhorn, A., et al., Integrin Activation Enables Sensitive Detection of Functional CD4+ and CD8+ T Cells: Application to Characterize SARS-CoV-2 Immunity. Frontiers in Immunology, 2021. 12.
- Cheryl Yi-Pin Lee, R.T.P.L., Laurent Renia, Serological Approaches for Covid-19: Epidemiologic Perspective on Surveillance and Control. Front Immunol, 2020. 11.
- Tai, W., et al., Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular & Molecular Immunology, 2020. 17(6): p. 613-620.
- VanBlargan, L.A., L. Goo, and T.C. Pierson, Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity. Microbiology and Molecular Biology Reviews, 2016. 80(4): p. 989-1010.