Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.
OBJECTIVE
Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions.


METHODS
We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events.


RESULTS
Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study subjects than in the controls, whereas the proportions of people with other characteristics were similar in both groups. None of the interviewed people had a history of food allergy to gelatin. The level of anti-gelatin IgE antibodies was significantly higher among study subjects than among controls, whereas the levels of IgE antibodies against egg and all 3 viral antigens did not differ significantly. Of 22 study subjects, 6 (27%) tested positive for anti-gelatin IgE, whereas none of the 27 controls did. The rate of anaphylactic reactions reported to VAERS after measles virus-containing immunization in the United States between 1991 and 1997 is 1.8 per 1 million doses distributed. No substantial increase in the number of reported allergic events after frequently used gelatin containing MMR and varicella vaccines could be observed during the first 4 years (1997-2000) since the introduction of diphtheria-tetanus-acellular pertussis vaccines for use in infancy.


CONCLUSIONS
Anaphylactic reactions to MMR in the United States are rare. The reporting rate has the same order of magnitude as estimates from other countries. Almost one fourth of patients with reported anaphylaxis after MMR seem to have hypersensitivity to gelatin in the vaccine. They may be at higher risk of developing anaphylaxis to subsequent doses of other gelatin-containing vaccines. These people should seek an allergy evaluation before such immunization.
Pool
Vitali
V
Vaccine Safety and Development Activity, Epidemiology and Surveillance Division, National Immunization Program, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. vpool@cdc.gov
Braun
M Miles
MM
Kelso
John M
JM
Mootrey
Gina
G
Chen
Robert T
RT
Yunginger
John W
JW
Jacobson
Robert M
RM
Gargiullo
Paul M
PM
D000707:Anaphylaxis / Q000453:epidemiology / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005780:Gelatin / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000276:immunology; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects*; D015995:Prevalence; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology
D022542:Measles-Mumps-Rubella Vaccine; D007073:Immunoglobulin E; D005780:Gelatin