The COVID-19 pandemic is the most destructive infectious disease outbreak in living memory, with over 30 million cases reported globally and over 900,000 deaths. In addition to the direct impact of the disease, the economic impact of the disease has been huge, as public health measures to contain or reduce the spread have led to country-wide lockdowns, forcing the closure or near closure of many sectors of the economy. In addition to the urgent and immediate response to the pandemic through public health measures and care for the ill, there is a pressing need for therapeutics, vaccines, and diagnostics, to improve management and ultimately control of the disease.
One of the biggest hurdles in the development of a vaccine against SARS CoV2 is that no one truly knows what a protective immune response looks like. Initial studies have been focused largely on the activity of neutralizing antibodies. Intriguingly, however, in both natural infection and in animal studies, survival is seen in the absence of neutralizing antibodies and death can still occur despite high levels of neutralizing antibodies, suggesting that neutralizing antibodies are neither neither necessary nor sufficient for survival. Only now, via studies in natural infection and animal models, are we beginning to better understand the extra-neutralizing function of antibodies and how they contribute to protection and exacerbation of disease
Given the potential important role of extra-neutralizing antibody functions in SARS CoV2 infection, SeromYx has devoted significant effort to adapting the Systems Serology suite of assays for the analysis of SARS CoV2–specific immune responses. To help accelerate the development of effective vaccines and immunotherapeutics, SeromYx is proud to offer this technology to vaccine and immunotherapeutic developers.
Our CoV2 efforts have been broadly focused into three areas:
Given the relatively recent emergence of SARS CoV2, we are only now beginning to understand how the developing immune response can contribute to both clearance of the infection and enhancement of disease. Much of the early research on natural SARS CoV2 infection focused on the development of neutralizing antibodies. While neutralizing antibodies were routinely detected in survivors of SARS CoV2 infection, these high titers of these antibodies were also frequently detected in individuals who did not survive the infection, suggesting that neutralization antibody titers alone cannot predict survival. More recent studies in both natural human infection and in animal models have suggested that extra-neutralizing antibody functions may also be important in driving resolution of disease, although a true correlate of protection has not yet been identified.
A true correlate of protection is urgently need as it can be used to guide vaccine design; therefore, SeromYx has partnered with Dr. Nahid Bhadelia at Boston University Medical Center and the National Emerging Infectious Diseases Laboratories at Boston University to establish a well-controlled cohort of patients grouped based on the severity of disease, from asymptomatic to severe, who are followed for several weeks through the resolution of disease. Importantly as the severity of COVID and the risk of death is disproportionately increased in minority populations, these groups are enriched in the study. With this cohort established, SeromYx will apply Systems Serology to identify potential correlates that are associated with disease severity and outcome.
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In additional to vaccines, monoclonal antibody–based therapeutics are rapidly being designed and used to treat and prevent SARS COV2 infection. While the leading monoclonal therapeutics are all neutralizing antibodies, it is unclear if neutralization alone is protective, particularly when used in a therapeutic setting (as opposed to a prophylactic setting). As the functional activity(ies) required for resolution of disease or prevention of infection remain unknown, the antibodies currently being tested are being developed with differing amounts of antibody functionality.
SeromYx has fully adapted the Systems Serology platform to evaluate the extra-neutralizing functional activities of monoclonal antibodies, including the addition of assays to quantify the potential of antibodies mediate antibody-dependent enhancement of infection and disease. SeromYx has partnered with a number of groups developing monoclonal antibody therapeutics to profile the effector function of candidate monoclonal antibodies, providing critical information to guide further development more efficacious therapeutics.
Traditionally, vaccine development has been a slow process, often taking a decade or more to develop, test, and license a new vaccine. Given the ongoing impact of the SARS CoV2 pandemic, the development cycle of SARS CoV2 vaccine has been rapidly accelerated, and the speed at which potential SARS CoV2 vaccines are being developed is unprecedented. However, working on an accelerated product development timeline necessitates changing the traditional approach to vaccine design.
Importantly, an accelerated timeline precludes a sequential approach to data acquisition as we no longer have the luxury of performing analyses to fully understand vaccine candidates after early trials are completed before larger efficacy trials begin and we no longer have time to complete post-hoc studies after adverse events are reported. Therefore, there is an urgent need to more deeply characterize candidate vaccines earlier in the development cycle, including identification of potential immunologic correlates of protection. While the generation of neutralizing antibodies remains the primary focus of all current vaccine candidates, an increasing number of SARS CoV2 vaccine developers are working with SeromYx to begin to evaluate extra-neutralizing activities to better define the total landscape of functions elicited by their antibodies generated by their vaccines.
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