Developing a COVID-19 skin test

CHATHAM, NJ—Tonix Pharmaceuticals Holding Corp. recently reported that the company has received a written response from the FDA to its Type B pre-investigational new drug (IND) meeting package describing a diagnostic skin test, TNX-2100, to measure the delayed-type hypersensitivity (DTH) reaction to SARS-CoV-2.

There is no standardized laboratory test available for measuring T cell immune responses, so Tonix has designed TNX-2100 for this purpose. Since T cell immunity to CoV-2 persists longer than antibody immunity, it’s sometimes present in the absence of a measurable antibody response, and is believed to provide an important element of protection against serious COVID-19 illness after infection with SARS-CoV-2.

“We believe TNX-2100 has the potential to measure T cell immunity to SARS-CoV-2 and therefore serve as an aid to COVID-19 diagnosis to support patient care, public health surveillance and vaccine trials,” noted Dr. Seth Lederman, president and CEO of Tonix. “Our proposed skin test has the potential to serve as: 1) a biomarker for cellular immunity and protective immunity; 2) a method to stratify participants in COVID-19 vaccine trials by immune status; 3) an endpoint in COVID-19 vaccine trials; and 4) a biomarker of durability of vaccine protection.”

TNX-2100 comprises three different mixtures of synthetic peptides designed to represent different protein components of the SARS-CoV-2 virus. TNX-2110 represents multiple proteins from the virus, TNX-2120 represents only the spike protein, and TNX-2130 represents non-spike proteins. 

Each of these tests is expected to be administered as part of the same procedure, in a similar manner as skin tests for tuberculosis. A thin gauge needle will be used to apply the three separate peptide mixtures intradermally, on the inner surface of the forearm between the wrist and the elbow. Each test should elicit a DTH response after around 48 hours in individuals with preexisting T cell immunity to peptides in that mixture. 

Individuals who have been infected by or exposed to SARS-CoV-2 are likely to respond to all three mixtures. In contrast, a successfully vaccinated individual who hasn’t been exposed to or infected by CoV-2 would probably respond only to TNX-2120, since the currently available vaccines only encode the spike protein. In the planned clinical protocol for testing TNX-2100, positive skin test controls will be used to confirm that study participants have intact T cell immunity, and are not immunodeficient.

In a typical positive test, the skin surrounding the injection site is expected to become indurated after approximately 48 hours. Induration above a threshold level would signify a positive result, and the diameter of the induration would indicate the amount of T cell immunity to the test peptides. DTH skin test responses are believed to reflect functional in vivo immunity. Clinical trials will correlate skin test results with clinical history and estimates about the sensitivity and specificity of the test as a marker of T cell immunity in individuals pre- and post-COVID-19 vaccination, individuals who have recovered from COVID-19, and some with active SARS-CoV-2 infection.

“Based on guidance provided by FDA in their written response, we believe we have the information necessary to respond to queries and file the IND application in the second quarter of 2021. The company has manufactured peptides under current good manufacturing process or cGMP,” added Dr. Herbert Harris, executive vice president of Translational Medicine at Tonix. “We expect clinical trials of TNX-2100 can be initiated, upon FDA clearance of the IND application, in the second half of 2021.”