Neutralizing antibodies against SARS-CoV-2's spike protein have been under the spotlight from the outset of the pandemic. Recognizing the potential value of neutralizing antibodies in protection from COVID-19, pharmaceutical companies quickly pivoted to produce recombinant monoclonal antibodies to the spike protein early in the pandemic (COVID-19 Biologics Tracker).
To date, several neutralizing antibodies initially identified in convalescent plasma have been developed as recombinant monoclonal antibody drugs. Most recently, Eli Lilly's neutralizing monoclonal antibody combos, bamlanivimab and etesevimab, were authorized by the FDA for treatment of adults and children (>12 years old) suffering from mild to moderate COVID-19.
Scientists have also increasingly focused on measuring serum neutralizing responses to SARS-CoV-2. By evaluating neutralizing antibodies in vaccinated and convalescent individuals, investigators hope to gain insight into how neutralizing activity correlates with protective immunity against COVID-19 (Muruato et al. 2020, Lau et al. 2021).
Neutralizing antibodies captured our attention once more in August 2020, when the FDA authorized the use of convalescent plasma to treat hospitalized COVID-19 patients. More recently, the FDA has revised the original emergency use authorization to include new specifications on the use and manufacture of convalescent plasma. Revisions to the initial authorization are motivated by findings from recent clinical trials. For example, a study by Libster et al. 2021 supports the efficacy of "high-titer" COVID-19 convalescent plasma in older adults experiencing mild illness when administered soon after symptom onset (Katz, 2021).
To ensure the use of "high-titer" COVID-19 convalescent plasma, the new FDA Emergency Use Authorization specifies that the plasma needs to be tested prior to use for treatment. Several tests, including GenScript's cPass™ neutralizing antibody detection kit have been authorized to support convalescent plasma screening. Among the recommended tests to qualify convalescent plasma, GenScript's cPass™ is the first FDA authorized test specific for detecting anti-SARS-CoV-2 neutralizing antibodies.
The plaque reduction assay is considered the "gold standard" for measuring how well serum antibodies neutralize SARS-CoV-2. However, this conventional approach relies on in vitro cellular infection by SARS-CoV-2. Therefore, from the user's standpoint at the clinic, this approach presents various challenges, including the need for a biosafety level 3 laboratory (BSL3), prolonged time to results (several days), and low-throughput.
In contrast, the cPass™ test, a Surrogate Virus Neutralization Test (sVNT) developed early during the pandemic by Professor Linfa Wang at Duke-NUS Medical School in collaboration with GenScript, solves many of the challenges associated with the conventional plaque reduction assay. First, the cPass™ test entirely relies on the use of purified proteins, namely ACE2 and Spike's RBD, eliminating the need for live SARS-CoV-2 virus. Second, the cPass™ test's time to results is significantly shortened to ~1 hour. Lastly, the cPass™ test's ELISA format provides a high-throughput approach to assaying convalescent plasma.
At the end of 2020, GenScript received FDA authorization for cPass™ use by laboratories certified under CLIA as a diagnostic test allowing health care providers to evaluate patients' viral exposure based on their neutralizing antibody responses. The recent FDA authorization for using GenScript's cPass™ kit to qualify convalescent plasma reiterates the critical role of neutralizing antibodies in protection from COVID-19.
One significant advantage of the cPass™ test is that it allows monitoring neutralizing responses to the vaccines currently used for immunization. Because several lines of evidence support the role of neutralizing antibodies in protective immunity against SARS-CoV-2, understanding how well different vaccines promote these responses will be vital for shaping future immunization decisions and public health measures. An organization that is currently leveraging the cPass™ test to monitor neutralizing antibodies in vaccinated individuals, cure-hubLLC has a created a dashboard with updated results from samples obtained from anonymous volunteer participants.
Comparison of neutralizing antibody responses following SARS-CoV-2 infection or vaccination with cPass™ kit. The cPass™ neutralization antibody test was used to analyze serum samples from eleven individuals as part of a study cohort consisting of: seven mRNA vaccine recipients, three naturally infected, and one uninfected-verified by PCR, participating in the Cure-Hub citizen science project. Baseline sample analysis was unavailable for two individuals in the natural infection group. Asterisks denote vaccinated individuals who received a second dose of the Moderna or Pfizer mRNA vaccines. The Cure-Hub citizen science project has created a dashboard containing updated information on the outcome of neutralizing antibody tests performed on serum from participating individuals who have been vaccinated or naturally infected with SARS-CoV-2 ( Vaccines vs. Natural Infection).
