Hepatitis B vaccines are made using baker’s yeast and residual quantities of yeast proteins are contained in the final product. Engerix-B (GlaxoSmithKline) contains no more than 5 mg per ml and Recombivax HB (Merck and Co.) contains no more than 1 mg per ml of yeast proteins.
Severe allergic reactions (including hives, difficulty breathing or low blood pressure) have been observed rarely after receipt of hepatitis B vaccine (about one case per 600,000 doses). However, allergy to yeast proteins does not appear to be the cause of these allergic reactions. References
Barbaud A, Tréchot P, Reichert-Pénétrat S, et al. Allergic mechanisms and urticaria/angioedema after hepatitis B immunization. Br J Dermatol. 1998;139:916-941.
Brightman CA, Scadding GK, Dumbreck LA, et al. Yeast-derived hepatitis B vaccine and yeast sensitivity. Lancet 1989;i:903.
Hudson TJ, Newkirk M, Gervais F, Shuster J. Adverse reaction to the recombinant hepatitis B vaccine. J Allergy Clin Immunol. 1991;88:821-822.
Lear JT, English JS. Anaphylaxis after hepatitis B immunization. Lancet 1995;345:1249.
Wiederman G, Scheiner O, Ambrosch F, et al. Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines. Int Arch Allergy Appl Immunol. 1988;85:130-132 .
It is true that natural infection almost always causes better immunity than vaccines. Whereas immunity from disease often follows a single natural infection, immunity from vaccines usually occurs only after several doses. However, the difference between vaccination and natural infection is the price paid for immunity.
The price paid for immunity after natural infection might be pneumonia from chickenpox, mental retardation from Haemophilus influenzae type b (Hib), pneumonia from pneumococcus, birth defects from rubella, liver cancer from hepatitis B virus, or death from measles.
Immunization with vaccines, like natural infections, induces long-lived immunity, but unlike natural infection, does not extract such a high price for immunity. Reviewed by: Paul A. Offit, MD Date: March 2008
The capacity of vaccines to either cause or exacerbate multiple sclerosis has been evaluated in several excellent studies.
Two large studies evaluated whether the hepatitis B vaccine causes multiple sclerosis or whether hepatitis B, tetanus or influenza vaccines worsen symptoms of multiple sclerosis. The first study evaluated 121,700 nurses followed from 1976 and 116,671 nurses followed from 1989 to identify 192 women with multiple sclerosis and 645 matched controls. There was no association between receiving the hepatitis B vaccine or the number of doses of hepatitis B vaccine and the risk of multiple sclerosis. The second study included 643 patients with a relapse of symptoms of multiple sclerosis occurring between 1993 and 1997 identified from the European Database for Multiple Sclerosis. The risk of relapse was not associated with the use of any of the vaccines studied (i.e., hepatitis B, tetanus and influenza vaccines).
Additional well-controlled studies also found that influenza vaccine did not exacerbate symptoms of multiple sclerosis. Indeed, in a study of 180 patients with relapsing multiple sclerosis, infection with influenza virus was more likely than immunization with influenza vaccine to cause a worsening of symptoms. Because natural influenza virus is well adapted to growth in people, and because influenza vaccine does not contain replicating virus, natural infection is more likely than vaccination to worsen symptoms of multiple sclerosis. Taken together, these findings suggest that influenza vaccine is more likely to prevent than cause exacerbations of multiple sclerosis.
Therefore, vaccines do not appear to either cause or exacerbate symptoms of multiple sclerosis. References
Ascherio A, Zhang SM, Hernan MA, et al. Hepatitis B vaccination and the risk of multiple sclerosis. N Engl J Med 2001;344:327-332.
Confavreux C, Suissa S, Saddier P, et al. Vaccinations and the risk of relapse in multiple sclerosis. N Engl J Med 2001;344:319-326.
De Keyser J, Zwanikken C, Boon M. Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis. J Neurol Sciences 1998;159:51-53.
Hall A, Kane M, Roure C, Meheus A. Multiple sclerosis and hepatitis B vaccine? Vaccine 1999;17:2473-2475.
Miller AE, Morgante LA, Buchwald LY, et al. A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis. Neurology 1997;48:312-314.
Moriabadi NF, Niewiesk S, Kruse N, et al. Influenza vaccination in MS: absence of T-cell response against white matter proteins. Neurology 2001;56:938-943. Reviewed by: Paul A. Offit, MD Date: March 2008
Gelatin is contained in some vaccines to protect vaccine viruses from adverse conditions such as freeze-drying or heat (see table below). Gelatin is a protein formed by boiling skin or connective tissue. Gelatin is used to stabilize vaccines so that they remain effective after manufacture. All gelatin contained in vaccines is porcine in origin.
In 1993, Kelso and co-workers reported the case of a 17-year-old girl in California who developed a severe allergic reaction (hives, low blood pressure, runny nose and lightheadedness) within five minutes of receiving an MMR (measles, mumps and rubella) vaccine. Her symptoms resolved after treatment with epinephrine. When later describing the event, the girl stated that it was “kind of like what happens when I eat Jell-O.” Subsequent testing found that the only component of the vaccine to which this girl was allergic was gelatin.
Studies in Japan confirmed the findings of Kelso and colleagues that severe allergic reactions to MMR vaccine were associated with the presence of antibodies in the blood directed against gelatin. Although the incidence of anaphylaxis to gelatin is extremely low (about one case per 2 million doses), gelatin is the most common identifiable cause of severe allergic reactions to vaccines.
Some people with severe allergic reactions to gelatin have a history of allergies to foods that contain gelatin. This is explained, in part, by similarities between the bovine gelatin contained in many foods and the porcine gelatin contained in vaccines. Therefore, it would be of value to know about possible allergies to gelatin before getting a vaccine that contains gelatin. People with severe allergies to gelatin should avoid gelatin-containing vaccines. References
Nakayama T, Aizawa C. Change in gelatin content of vaccines associated with reduction in reports of allergic reactions. J Allergy Clin Immunol. 2000;106:591-592.
Sakaguchi M, Nakayama T, Fujita H, et al. Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin. Vaccine 2001;19:431-436.
Sakaguchi M, Nakayama T, Inouye S. Food allergy to gelatin in children with systemic immediate-type reactions, including anaphylaxis, to vaccines. J Allergy Clin Immunol. 1996;98:1058-1061.
Sakaguchi M, Yamanaka T, Ikeda K, et al. IgE-mediated systemic reactions to gelatin included in the varicella vaccine. J Allergy Clin Immunol. 1997;99:263-264.
Sakaguchi M, Hori H, Ebihara T, et al. Reactivity of the immunoglobulin E in bovine gelatin-sensitive children to gelatins from other animals. Immunology 1999;96:286-290.
Sakai Y, Yamoto R, Onuma M, et al. Non-antigenic and low allergic gelatin produced by specific digestion with enzyme-coupled matrix. Biol Pharm Bull. 1998;21:330-334. Reviewed by: Paul A. Offit, MD Date: March 2008
Egg allergies occur in about 0.5 percent of the population and in about 5 percent of children with allergies. Because influenza and yellow fever vaccines are both made in eggs, egg proteins (primarily ovalbumin) are present in the final product. Residual quantities of egg proteins found in the influenza vaccine (i.e., about 0.02-1.0 ug per dose) are sufficient to induce severe and rarely fatal hypersensitivity reactions in children with egg allergies. Unfortunately, people with egg allergies also have other diseases (such as asthma) that are associated with a high risk of severe and occasionally fatal influenza infection. For this reason, protocols have been developed to administer influenza vaccine safely to people with severe egg allergies.
In contrast to influenza vaccine, measles and mumps vaccines are propagated in chick embryo cells in culture — not in eggs. The quantity of residual egg proteins found in the MMR (measles, mumps and rubella) vaccine is about 40 pg — a quantity at least 500-fold less than those found for influenza vaccines. The quantity of egg proteins found in MMR is not sufficient to cause severe allergic reactions, and children with severe egg allergies can receive measles and mumps vaccines safely. References
Bierman CW, Shapiro GG, Pierson WE, et al. Safety of influenza vaccination in allergic children. J Infect Dis. 1977;136:S652-S655.
Fasano MB, Wood RA, Cooke SK, Sampson HA. Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine. J Pediatr. 1992;120:878-881.
Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25-44.
Glezen WP, Greenberg SB, Atmar RL, et al. Impact of respiratory virus infection on persons with underlying conditions. JAMA 2000;283:499-505.
James JM, Zeiger RS, Lester MR, et al. Safe administration of influenza vaccine to patients with egg allergy. J Pediatr. 1998;133:624-628.
Murphy KR, Strunk RC. Safe administration of influenza vaccine in asthmatic children hypersensitive to egg proteins. J Pediatr. 1985;106:931-933.
Ratner B, Untracht S. Egg allergy in children. Am J Dis Child. 1952;83:309-316.
Zieger RS. Current issues with influenza vaccination in egg allergy. J Allergy Clin Immunol. 2002;110:834-840. Reviewed by: Paul A. Offit, MD Date: March 2008
Small children who are shaken forcefully in rage can develop bleeding around the brain (subdural hematomas) and bleeding on the back of the eye (retinal hemorrhages). Some lawyers have chosen to defend people accused of abusing children by saying that bleeding was caused by the pertussis component of the DTP vaccine. However, no evidence exists to support this contention. Neither pertussis nor the pertussis vaccine cause bleeding around the brain or on the back of the eye — only forceful shaking does this. Reviewed by: Paul A. Offit, MD Date: March 2008
The relationship between vaccines and diabetes has been the subject of several excellent studies.
The hypothesis that the timing of vaccines either causes or prevents diabetes was tested in 21,421 children who received the Hib conjugate vaccine between 1988 and 1990 in the United States. These children were followed for 10 years after receiving the Hib vaccine. The risk of diabetes was indistinguishable from a group of 22,557 children who did not receive the Hib vaccine.
Another excellent study evaluating the relationship between vaccines and diabetes was performed using data from the Vaccine Safety DataLink. Four large HMOs were used to identify children with diabetes born between 1988 and 1997. All four HMOs maintained registries of children with diabetes and cases were confirmed by means of medical records. Investigators compared 252 cases of diabetes with 768 matched controls. Children who received whole-cell pertussis, MMR, Hib, hepatitis B or varicella vaccines were not at greater risk for diabetes than children who did not receive those vaccines. In accord with the Vaccine Safety DataLink study, several other well-controlled retrospective studies found that immunizations were not associated with an increased risk of developing diabetes.
Therefore, the best available evidence does not support the hypothesis that vaccines cause diabetes. References
Black SB, Lewis E, Shinefield H, et al. Lack of association between receipt of conjugate Haemophilus influenzae type b vaccine (HbOC) in infancy and risk of type 1 (juvenile onset) diabetes: long term follow-up of the HbOC efficacy trial cohort. Pediatr Infect Dis J 2002;21:568-569.
DeStefano F, Mullooly JP, Okoro CA, et al. Childhood vaccinations, vaccination timing, and risk of type 1 diabetes mellitus. Pediatrics 2001;108:(6). URL:http://www.pediatrics.org/cgi/content/full/108/6/e112
Graves PM, Barriga KJ, Norris JM, et al. Lack of association between early childhood immunizations and b-cell autoimmunity. Diabetes Care 1999;22:1694-1697.
Heijbel H, Chen RT, Dahlquist G. Cumulative incidence of childhood-onset IDDM is unaffected by pertussis immunization. Diabetes Care 1997;20:173-175.
Hummel M, Fuchtenbusch M, Schenker M, et al. No major association between breast-feeding, vaccinations, and childhood viral diseases with early islet autoimmunity in the German BABYDIAB study. Diabetes Care 2000;23:969-974.
Institute for Vaccine Safety Diabetes Workshop Panel. Childhood immunizations and type 1 diabetes: summary of an Institute for Vaccine Safety Workshop. Pediatr Infect Dis J 1999;18:217-222. Reviewed by: Paul A. Offit, MD Date: March 2008
Occasional magazine and newspaper stories have claimed that the Lyme vaccine, available in the United States between 1998 and 2002, was a cause of chronic arthritis (swelling of the joints).
Two excellent, well-controlled studies were performed evaluating the safety of Lyme vaccine. Lyme vaccines were compared with placebo in 10,936 and 10,305 subjects, respectively. Participants were followed for 20 to 24 months. There were no significant differences in the type or frequency of joint symptoms in vaccine and placebo recipients in either study. Similarly, patients with a previous history of Lyme disease did not experience an increased frequency of joint symptoms compared with controls.
Therefore, the best evidence does not support the hypothesis that Lyme vaccine caused arthritis. Unfortunately, despite its excellent safety record, the Lyme vaccine is no longer available. References
Lathrop SL, Ball R, Haber P, et al. Adverse event reports following vaccination for Lyme disease: December 1998-July 2000. Vaccine 2002;20:1603-1608.
Sigal LH, Zahradnik JM, Lavin P, et al. A vaccine consisting of recombinant Borrelia burgdorferi outer surface protein A to prevent Lyme disease. N Engl J Med 1998;339:216-222.
Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. N Engl J Med 1998;339:209-215. Reviewed by: Paul A. Offit, MD Date: March 2008
Several large studies have investigated the relationship between vaccines and allergies.
One well-controlled study was performed using the computerized records of children born between 1991 and 1997 who were enrolled in four large health maintenance organizations (HMOs). Researchers identified 18,407 children with asthma. The risk for asthma was not greater in children who received DTP vaccine, oral polio vaccine, MMR vaccine, Hib vaccine or hepatitis B vaccine compared with children who did not receive these vaccines.
Another large well-controlled study prospectively evaluated the risk of allergies following receipt of the pertussis vaccine in 669 children. Infants were randomized to receive one of three different diphtheria-tetanus-pertussis vaccines or a control vaccine that did not contain pertussis beginning at 2 months of age. Children were followed for about two and a half years and the risk of allergies was determined by parent questionnaires and examination of medical records. Allergic disorders studied included asthma, skin reactions, hay fever, hives and food allergies. No differences in the incidence of allergic diseases were observed in children who did or did not receive pertussis vaccine. Of interest, children with natural pertussis infections were more likely to develop allergic diseases than children not infected with pertussis.
Taken together, these studies fail to support the hypothesis that vaccines cause allergic diseases. References
Anderson HR, Poloniecki JD, Strachan DP, et al. Immunization and symptoms of atopic disease in children: results from the international study of asthma and allergies in children. Am J Public Health 2001;91:1126-1129.
DeStefano F, Gu D, Kramarz P, et al. Childhood vaccinations and the risk of asthma. Pediatr Infect Dis J 2002;21:498-504.
Gruber C, Kulig M, Bergmann R, et al. Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestations in longitudinally followed early Bacille Calmette-Guerin-vaccinated and nonvaccinated children. Pediatrics 2001;107:e36.
Kramarz P, DeStefano F, Gargiullo PM, et al. Does influenza vaccination exacerbate asthma? Arch Fam Med 2000;9:617-623.
Nilsson L, Kjellman N, Bjorksten B. A randomized controlled trial of the effect of pertussis vaccines on atopic disease. Arch Pediatr Adolesc Med 1998;152:734-738.
Nicholson KG, Nguyen-Van-Tam JS, Ahmed AH, et al. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Lancet 1998;351:326-331.
Reid DW, Bromly CL, Stenton SC, et al. A double-blind placebo-controlled studyof the effect of influenza vaccination on airway responsiveness in asthma. Resp Med 1998;92:1010-1011.
Wickens K, Crane J, Kemp T, et al. A case-control study of risk factors for asthma in New Zealand children. Aust NZ Public Health 2001;25:44-49. Reviewed by: Paul A. Offit, MD Date: March 2008