Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: insights into vaccine-associated Guillain-Barré syndrome.
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-GM(1)) 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-GM(1) 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-GM(1) 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-GM(1) antibodies in mice, as did vaccines from 1991-1992 and 2004-2005. Preliminary studies suggest that the influenza HA induces anti-GM(1) antibodies.


CONCLUSIONS
Influenza vaccines contain structures that can induce anti-GM(1) 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.
Nachamkin
Irving
I
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA. nachamki@mail.med.upenn.edu
Shadomy
Sean V
SV
Moran
Anthony P
AP
Cox
Nancy
N
Fitzgerald
Collette
C
Ung
Huong
H
Corcoran
Adrian T
AT
Iskander
John K
JK
Schonberger
Lawrence B
LB
Chen
Robert T
RT
D000818:Animals; D000917:Antibody Formation; D016123:Campylobacter jejuni / Q000235:genetics / Q000276:immunology; D004269:DNA, Bacterial / Q000302:isolation & purification; D005732:Gangliosides / Q000276:immunology*; D016537:Gangliosidosis, GM1 / Q000276:immunology; D006017:Glycolipids / Q000276:immunology; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects*; D051379:Mice; D008809:Mice, Inbred C3H; D016133:Polymerase Chain Reaction; D019318:Porcine Reproductive and Respiratory Syndrome / Q000276:immunology; D013552:Swine
D004269:DNA, Bacterial; D005732:Gangliosides; D006017:Glycolipids; D007252:Influenza Vaccines