Do Vaccines Cause Serum Sickness?

Updated November 9, 2023



Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause serum sickness.

Epidemiological Evidence

The 2012 report by the Institute of Medicine (IOM), now called the National Academy of Medicine (NAM), found no relevant studies of quality in the literature assessing serum sickness and diphtheria, tetanus or pertussis vaccines 1. No relevant studies of quality have been published since this report.

Proposed Biological Mechanism

Formation of immune complexes is a known mechanism in the development of serum sickness. Another mechanism that could potentially contribute to development of serum sickness is activation of the complement system, in which a cascade of proteolysis and successive release of cytokines functions to amplify the immune response but can damage host cells if not properly regulated 1.

The 2012 IOM report described one case of serum sickness after a diphtheria and tetanus vaccine 2; however, the IOM concluded that this mechanistic evidence was weak. The IOM also concluded that there was no mechanistic evidence for an association between serum sickness and pertussis vaccine 1. Since publication of the 2012 IOM report, a case of serum sickness after H1N1 pandemic influenza vaccine was also described in the literature 3.

* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.


1.         Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.

2.         Daschbach RJ. Serum sickness and tetanus immunization. Jama 1972; 220(12): 1619.

3.         Bonds RS, Kelly BC. Severe serum sickness after H1N1 influenza vaccination. Am J Med Sci 2013; 345(5): 412-3.