The purpose of this case report is to describe a possible association between Guillain–Barré syndrome (GBS) and the newly approved 21-valent pneumococcal conjugate vaccine (PCV21).

Pneumococcal conjugate vaccines (PCVs) including PCV13, PCV15, and PCV20 are widely used to prevent pneumococcal infection. On June 17, 2024, the U.S. Food and Drug Administration (FDA) approved the 21-valent pneumococcal conjugate vaccine (PCV21; Capvaxive; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. Unlike PCV20, PCV21 is not simply PCV20 plus one additional serotype. PCV21 was specifically designed to target invasive pneumococcal disease (IPD) serotypes that predominantly affect adults. Although PCV20 and PCV21 share 10 common serotypes, each also includes additional unique ones—11 in PCV21 and 10 in PCV20. 

As PCV21 was only recently approved in 2024, post-marketing data remain limited. Here, we present a case report describing a possible association between PCV21 and GBS.

We report a 64-year-old male who developed progressive ascending weakness and paresthesias 7 days after receiving PCV21 vaccination. Neurologic examination revealed areflexia, hyporeflexia, symmetric weakness, and sensory deficits.

Laboratory evaluation demonstrated albuminocytologic dissociation. Nerve conduction studies were consistent with AIDP.

The patient was diagnosed with GBS and treated with IVIG without obvious improvement. His weakness progressed, reaching a nadir of grade 1/5 strength in the lower extremities, raising concern for impending respiratory failure. Therapy was switched to plasma exchange.

Extensive evaluation, including infectious, metabolic, and autoimmune workup, was unrevealing, strengthening the temporal association with recent PCV21 vaccination.

We report a case of GBS following a single dose of newly introduced PCV21. Continued case reporting and post-marketing surveillance are essential to monitor the safety profile. It is also important to emphasize that the benefits of vaccination still outweigh the potential risks.