Anti-Ganglioside Antibody Induction by Swine (A/NJ/1976/H1N1) and Other Influenza Vaccines: Insights into Vaccine-Associated Guillain-Barré Syndrome

• Published in: The Journal of infectious diseases 2008-07, Vol.198 (2), p.226-233
• Main Authors: Nachamkin, Irving, Shadomy, Sean V., Moran, Anthony P., Cox, Nancy, Fitzgerald, Collette, Ung, Huong, Corcoran, Adrian T., Iskander, John K., Schonberger, Lawrence B., Chen, Robert T.
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation; Applied microbiology; Biological and medical sciences; Campylobacter jejuni; Campylobacter jejuni - genetics; Campylobacter jejuni - immunology; DNA, Bacterial - isolation & purification; Fundamental and applied biological sciences. Psychology; Gangliosides - immunology; Gangliosidosis, GM1 - immunology; Glycolipids - immunology; Guillain-Barre Syndrome - immunology; Hemagglutination Inhibition Tests; Humans; Infectious diseases; Influenza A virus - immunology; Influenza Vaccines - adverse effects; Medical sciences; Mice; Mice, Inbred C3H; Microbiology; Polymerase Chain Reaction; Porcine Reproductive and Respiratory Syndrome - immunology; Swine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/589624

Background. Receipt of an A/NJ/1976/H1N1 “swine flu” vaccine in 1976, unlike receipt of influenza vaccines used in subsequent years, was strongly associated with the development of the neurologic disorder Guillain-Barré syndrome (GBS). Anti-ganglioside antibodies (e.g., anti-GM1) are associated with the development of GBS, and we hypothesized that the swine flu vaccine contained contaminating moieties (such as Campylobacter jejuni antigens that mimic human gangliosides or other vaccine components) that elicited an anti-GM1 antibody response in susceptible recipients. Methods. Surviving samples of monovalent and bivalent 1976 vaccine, comprising those from 3 manufacturers and 11 lot numbers, along with several contemporary vaccines were tested for hemagglutinin (HA) activity, the presence of Campylobacter DNA, and the ability to induce anti-Campylobacter and anti-GM1 antibodies after inoculation into C3H/HeN mice. Results. We found that, although C. jejuni was not detected in 1976 swine flu vaccines, these vaccines induced anti-GM1 antibodies in mice, as did vaccines from 1991–1992 and 2004–2005. Preliminary studies suggest that the influenza HA induces anti-GM1 antibodies. Conclusions. Influenza vaccines contain structures that can induce anti-GM1 antibodies after inoculation into mice. Further research into influenza vaccine components that elicit anti-ganglioside responses and the role played by these antibodies (if any) in vaccine-associated GBS is warranted.