GSK's Shingrix, the world's only shingles vaccine that can be given to immunocompromised individuals such as cancer patients, is notorious for causing pain, unlike any other vaccine, from the moment it is given to three to four days afterward.

So why is it so painful to receive Shingrix, a recombinant zoster vaccine (RZV), unlike other vaccines?

"The pain may be caused by QS-21, one of the immune-boosting ingredients in Shingrix," a GSK Korea official said while explaining the reason.

Shingrix is a subcutaneous injection that combines an “immune booster”' with a “non-living antigen,” and the pain may be caused by QS-21, one of the immune-boosting ingredients extracted from the soapbark tree (Quillaja saponaria), the official added.

This is not unique to Shingrix but is a common problem with vaccines that contain QS-21, according to a study by the Korea Institute of Science and Technology Information (KISTI) that dealt with the "action and development of immune supplements.

QS-21 is also found in Novavax's Covid-19 vaccine, which can cause short-term injection site pain, as confirmed by reports of adverse reactions to Novavax's Covid-19 vaccine.

According to Professor Lee Pyung-bok of the Department of Anesthesiology and Pain Medicine at Seoul National University Bundang Hospital, painful injections are usually caused by the drug's large molecular weight or a mismatch between the body and the drug's pH (a measure of acidity).

However, the GSK Korea official dismissed the relationship between molecular weight and pH of Shingrix and vaccine injection pain.

Another indirect study supports the claim that the plant extract QS-21 can be zoned down as the cause of pain during and after the Shingrix shot.

"In a phase 2 study of a shingles vaccine candidate, we saw a difference in pain incidence between the formulation with and without the immune-boosting agent," the GSK official said.

What can be done to minimize the pain caused by Shingrix, then?

"It's helpful to take Tylenol for three to four days when taking Shingrix," Professor Lee said. "In practice, patients are prescribed a three- to four-day supply of Tylenol when taking Shingrix."