Influenza Vaccine in Children and Adults With Egg Allergy

Release Date: April 1, 2014

Expiration Date: April 30, 2016

FACULTY:

Ronald A. Prada, PharmD Candidate 2014
St. John's University College of
Pharmacy and Health Sciences
Jamaica, New York

Gladys El-Chaar, BS, PharmD
Associate Clinical Professor, Department
of Clinical Pharmacy Practice
St. John's University College of
Pharmacy and Health Sciences
Jamaica, New York
Pediatric Pharmacotherapist
Department of Pharmacy
Winthrop University Hospital
Mineola, New York

FACULTY DISCLOSURE STATEMENTS:

Mr. Prada and Dr. El-Chaar have no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

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Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To educate pharmacists on the changes to the contraindications of influenza vaccine administration in children and adults with egg allergy.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Describe the recent changes in the contraindications to the administration of influenza vaccine in children and adults with egg allergy.
  2. Interpret the data behind the safety of influenza vaccine administration in children and adults with allergy to eggs and the role of ovalbumin.
  3. Discuss the role of the new influenza vaccines in children and adults with severe, anaphylactic egg allergy.

ABSTRACT: Contraindications to receiving the influenza vaccine had included allergy to eggs, due to the growth of influenza antigens in chick embryos during vaccine development. Ovalbumin, which is contained in these embryos, had been present in greater amounts in previous formulations. Studies have shown that patients with a history of egg allergy had tolerated these influenza vaccines. Hence, immunization guidelines have changed and no longer list mild egg allergy as a contraindication to receiving the vaccine. Two new vaccines, Flublok and Flucelvax, present alternatives for adults with severe egg allergy; however, for children with severe egg allergy, a referral to a pediatric allergist is still recommended.

Infection with influenza is associated with seasonal epidemics around the world every year. Influenza viruses are classified as either type A, B, or C based on proteins, hemagglutinins (HAs), and neuraminidases found on the surface of the virus. These are further divided into subcategories according to their surface protein subtypes. The virus, when inhaled by a susceptible host, binds to respiratory epithelial cells through HA. Normal cell function is disrupted and new virions are produced as a result. Cleavage of these new virions by neuraminidase allows the infection to spread.1

The influenza virus is highly contagious and can easily be transmitted from one person to another through droplet contact. Infection can cause serious illness and may lead to hospitalization, morbidity, and mortality, especially in children >5 years of age.2,3 According to the CDC, the number of influenza-associated deaths in children in the United States within a single influenza season has ranged from 35 to 348 from 2009 through 2013.2,4,5 Prior to the current influenza season, influenza vaccines were available in inactivated or live attenuated trivalent forms (trivalent inactivated virus, TIV) that included two strains of influenza type A and one strain of type B.

For the 2013-2014 influenza season, several quadrivalent formulations were available, covering two strains of influenza types A and B because of limitation of cross-protection from one influenza B strain to another and the difficulty in predicting the specific strain likely to be circulating in a given season.2 Either trivalent or quadrivalent vaccines could be given in the 2013-2014 influenza season according to availability to avoid delays in administration.6 Effectiveness of TIV formulations can vary widely depending on a number of contributing factors, including the age and health of the individual being immunized and the match between the circulating influenza virus and the vaccine. The effectiveness of trivalent influenza vaccine is approximately 60% in preventing influenza-related illness.7

Guidelines for Immunizations Against Influenza in Children

The CDC and the American Academy of Pediatrics (AAP) recommend immunization against influenza viruses to all adults and children starting from 6 months of age, on a yearly basis because of antigenic drifts in influenza strains.6,8 In children 6 months to 9 years of age receiving the influenza vaccine for the first time, two doses, separated by at least 1 month during the same influenza season, are required to enhance antibody response.6 During the first 6 months of life, the influenza vaccine is not indicated, as maternal antibodies provide some immunity against influenza transplacentally and through breastfeeding. Immunization of women during pregnancy prevents influenza-related hospitalizations in 90% of their infants.9 During this period of time, the CDC advises that alternative precautions be taken to protect the infant from infection, such as hand-washing and avoiding sick contacts.10

Influenza Vaccine and Egg Allergy

Contraindications to influenza vaccine administration include allergy to eggs and other vaccine components. Egg allergy affects an estimated 1% to 2% of children in the U.S.; however, approximately 70% of this population outgrows this allergy by adolescence.11,12 It is important to differentiate a true allergy as compared to an adverse reaction to eggs. An allergic reaction may range from a localized dermatologic response with pruritus and hives to a more severe one, such as an anaphylactic reaction, with symptoms of chest discomfort and tightness, difficulty breathing, and/or swelling of the face, eyes, or tongue.13

Until recently, all influenza vaccines approved for use in the U.S. were prepared via inoculation of the virus into the embryos of chicken eggs.2 In commercial processing, a small amount of ovalbumin, a protein and a primary allergen in patients with egg allergy, was retained in the vaccines.14 In the past, the AAP guidelines advised against the administration of influenza vaccine in children with a severe, anaphylactic reaction to eggs until a skin test was performed using a diluted vaccine dose.15 In the event of a positive skin test and if immunization was essential, one option was to use multiple graded-vaccine doses by clinicians trained in the treatment of anaphylaxis, in a setting that allowed full resuscitation, through an allergist referral.15 This additional step required for safe vaccine administration in a vulnerable pediatric population at higher risk of complications from influenza than adults, where egg allergy is more prevalent than in adults, may present a barrier to providing protection against the influenza viruses.16

Influenza Vaccine Safety in Persons With Egg Allergy

The following studies examined the safety of the seasonal influenza vaccine grown in embryonated eggs in patients with egg allergy.

James et al: This study was the first to examine the safety of a graded-dose approach of the influenza vaccine for children and adults with egg allergy.16 The multicenter trial included 83 subjects with egg allergy as compared to 124 control subjects ranging in age from 1 to 78.5 years, and spanned three influenza seasons from 1994 through 1997. Exclusion criteria were poorly controlled asthma (forced expiratory volume in 1 second <70% of best effort), fever with a temperature >101°F, and immune deficiency or neoplastic disease. Influenza formulations used in the beginning of the study contained 0.02 to 1.2 mcg/mL of ovalbumin (Parke-Davis), while in the later seasons ovalbumin concentrations ranged from 1 to 42 mcg/mL (Wyeth-Ayerst and Connaught), using an inhibition enzyme-linked immunosorbent assay (ELISA) test. The first dose (10% of the full dose) was given followed by the remaining dose 30 minutes later, intramuscularly. Specific formulations were not disclosed by brand, but by manufacturer names. Of the 83 subjects, 27 had a history of anaphylaxis to eggs, manifested by urticaria, wheezing, laryngeal edema, and/or hypotension following egg consumption, while the remaining 56 had either a positive history and positive skin test response or a positive response to an oral egg challenge.16

Subjects were followed up to 48 hours after immunization to determine adverse effects.16 None of the subjects developed a serious or anaphylactic reaction to the influenza vaccine. In children ≤8 years of age, where two influenza doses are given, two patients experienced hives, one patient had some throat itching, cough, and wheeze after the first dose, another patient had cough and wheeze, while two children had small hives. All adverse effects resolved without interventions and the patients tolerated their second booster dose without incident. Four adults and children older than 8 years of age had adverse effects, one with delayed pruritus, one with fussiness, one with some upper respiratory infection (URI) symptoms, and one with delayed erythema at the injection site, which required the use of hydroxyzine. All adverse effects resolved. Control subjects also experienced erythema (2), emesis and fever (1), and urticarial reaction (1).16

The authors confirmed the safety of influenza vaccine administration even to those with a previous anaphylactic reaction to eggs or egg products; however, they recommended knowledge of the ovalbumin concentrations prior to immunization to help maintain patient safety.16 This study was well designed, where the subjects with a history of egg allergy had confirmations of this allergy, some patients with an anaphylactic reaction to eggs were enrolled, and all tolerated the vaccine very well.16

Webb et al: In the 2009-2010 influenza season, a multicenter, retrospective review of the safety of the H1N1 vaccine in patients with egg allergy was performed at four clinics.17 Subjects previously diagnosed with egg allergy were given a skin prick test (SPT) or egg-specific serum or skin immunoglobulin E (IgE) test to confirm allergenicity. Patients who reported being able to tolerate baked eggs were skin-tested at the discretion of the clinician because these patients generally can tolerate egg protein in small amounts. Patients with a negative SPT received a full dose as a single influenza vaccine injection, whereas patients with a positive or equivocal SPT were given two aliquots (first, 10% of the full dose, then the remaining 90%, 30 minutes later). Seasonal influenza vaccines were used from three different manufacturers and 21 lots. Fluzone was used in 90% of doses due to its FDA approval in children aged <4 years. Information on other vaccine brands or the H1N1 vaccine was not provided. Subjects were observed for 30 minutes after immunization and the following day to rule out a delayed reaction.17

One-hundred and fifty-two patients were enrolled in the study, and since children <9 years of age require a booster dose, 292 doses were administered.17 Exclusion criteria were not described. Patients were between 7 months and 30 years of age. Thirty-four patients had a history of anaphylaxis to eggs with hypotension, or a combination of respiratory, skin, or prolonged gastrointestinal (GI) involvement; 87 patients had a history of GI or skin manifestation; 31 patients had a negative history of allergy to eggs, but with positive IgE or SPT documentation. Ninety-seven percent of the vaccinations were given as a single dose. None of the subjects developed systemic reactions, including those patients with a history of severe egg allergy and anaphylaxis. Mild, local reactions occurred in two patients. Ovalbumin content was estimated to be approximately 1.421 mcg/mL.17

Chung et al: Researchers retrospectively reviewed the safety of the influenza vaccine administered in two doses.18 To confirm egg allergy, an SPT or radioallergosorbent test (RAST) was conducted. Children with a history of anaphylaxis were excluded from the study. During the 2002-2003 through the 2008- 2009 influenza seasons, 171 children aged 6 months to 18 years with documented egg allergy who received the influenza vaccine were reviewed. There was no information on the type of influenza vaccine given. Most egg allergies consisted of dermatologic reactions, including hives, rash, and swelling; some children had GI symptoms (abdominal pain, emesis, diarrhea), while others had respiratory symptoms (wheezing, coughing, shortness of breath, or rhinitis).

In the 2006-2007 influenza season, the practice changed to omit testing for egg allergy prior to administering the influenza vaccine. As previously described, doses were split and given in two aliquots 10% (followed by 90% of the dose), and the children were observed for 30 minutes after each dose. Children who underwent skin testing prior to influenza vaccine administration were compared to some who did not undergo skin testing. Localized reactions, including wheals and flares at the injection site, occurred in 29 of the 36 patients who were reported to have an adverse effect. Seven patients developed wheezing, eczema exacerbation, or hives, regardless of whether allergy testing was done prior to vaccine administration. None of the patients developed an anaphylactic reaction to the vaccine. The second dose of the vaccine was not administered to these patients. The remainder of the patients tolerated the vaccine. The exclusion of anaphylactic reactions to eggs limited the application of this study. The authors determined that skin testing was not predictive of a subsequent reaction to the vaccine.18

H1N1 Vaccine: In response to the 2009 pandemic of the H1N1 strain of type A influenza, the CDC's Advisory Committee on Immunization Practices (ACIP) recommended specific groups of patients to receive the H1N1 vaccine, because it was anticipated that the 2009-2010 trivalent seasonal vaccine would not provide adequate protection.19 Included in the recommendations were pregnant women, household contacts and caregivers of children aged <6 months, and all individuals 6 months through 24 years of age. Fears of greater numbers of infections and complications, especially in children, necessitated a harder look at the association between egg allergy and the influenza vaccine, since young children have a proportionally higher number of egg allergies. The monovalent H1N1 vaccine was also produced by inoculation of live virus into embryonated chicken eggs.

Given the contraindication to receiving the influenza vaccine by children with egg allergy and the need to provide protection against the H1N1 virus to vulnerable patients, the Canadian Society of Allergy and Clinical Immunology encouraged the immunization of children with mild egg allergy consisting of mild GI or dermatologic manifestations without prior testing of the patients as long as the egg protein content in the vaccine was <1.2 mcg/mL.20 Other, more severe egg-allergy manifestations such as cardiovascular and/or respiratory symptoms would necessitate splitting the vaccine dose into two, with monitoring for 60 minutes after the final dose,20 as previously described by James et al.16

Gagnon et al: In a large, prospective, observational study performed in October to December 2009, Gagnon et al assessed the primary outcome of anaphylaxis in children ranging in age from <2 years to >12 years with confirmed egg allergy compared to 393 control subjects without egg allergy.21 Patients received divided doses of the monovalent A/H1N1 vaccine Arepanrix if they were considered to be at high risk for anaphylaxis by a history of cardiorespiratory involvement or uncontrolled asthma; otherwise, a single dose was administered. Ovalbumin content of the vaccine was <0.03 mcg/mL. Vaccine doses were given according to the manufacturer guidelines. Patients were observed for 60 minutes post immunization, and follow-up was done by telephone 24 hours later. Of the 1,046 subjects observed, 246 were excluded from analysis because of a lack of egg allergy and a negative skin or serologic response. Of the 830 remaining patients with egg allergy, 9% required divided dose administration.21

Following immunization, none of the patients developed an anaphylactic reaction.21 In the group with egg allergy, 17 (2%) patients developed adverse effects, including cutaneous reactions (13, including 1 patient with angioedema, 1 with urticaria, and 1 with ocular pruritus who were treated successfully with antihistamines); abdominal pain (1); and respiratory symptoms (3) who received albuterol for their symptoms of cough, hoarseness, and mild dyspnea. Signs and symptoms of egg allergy in the control group were similar to those reported in the group with egg allergy. The investigators concluded that generally, vaccination of egg-allergic patients with the adjuvanted H1N1 vaccine is safe.21

This study design was observational. Therefore, bias would have been possible, inclusion criteria were not clearly defined, and subject ages were provided in categories; however, 55% of subjects were <5 years old, representing the pediatric population well.21 It is also possible that some patients with a previous anaphylactic reaction to eggs may have elected not to be immunized.

Howe et al: The safety of the seasonal and H1N1 vaccines in children aged 6 to 36 months with egg allergy was assessed in a retrospective, followed by a prospective, study.22 The retrospective arm spanned the years 2004 through 2009 and included children with egg allergy evaluated after receiving the trivalent seasonal influenza vaccine. Children were included if they had evidence of egg allergy during a previous influenza immunization season. Of the 193 children identified, 135 met the inclusion criteria and received the seasonal trivalent influenza vaccine. Information on the specific vaccine formulation was not provided, nor was the ovalbumin content. Seventeen children had a documented anaphylactic reaction to eggs, 14 of whom received the influenza vaccine without adverse effects; the remaining patients never received the vaccine due to parental or clinician preference. Of the patients without a history of anaphylaxis, seven experienced minor adverse effects, ranging from localized reactions to diarrhea, and some patients developed hives, without further details provided.22

The prospective arm included 69 children with egg allergy, 13 with a history of anaphylaxis, and 14 without egg allergy who received the trivalent vaccine during the 2009-2010 influenza season.22 Children were tested for egg allergy using an SPT and, if positive, the vaccine was given in two steps. No further information was provided regarding the specifics of the administration method or the formulation used, except that ovalbumin content was tested as containing 0.3 to 1.087 mcg/mL. Inclusion and exclusion criteria were not specified beyond an egg allergy. Sixty-eight of these children tolerated the vaccine as a single dose (not divided). The authors did not provide further information on the remaining patient. While no serious allergic reactions or anaphylaxis occurred, two children with a history of allergy developed lip and mouth itching and scattered hives, and two children in the control group also developed hives and fever or rash, despite a negative history of egg allergy. None of the children with a history of anaphylaxis developed adverse effects. Again, this limited study further supports the safety of the influenza vaccine in patients with a history of anaphylaxis to eggs and questions the value of the SPT in predicting egg allergy, hence vaccine tolerability.22

Greenhawt et al: The safety of the seasonal influenza vaccine administered in children with severe egg allergy from 2010 through 2012 was assessed.23 The study had two phases, the first of which was a prospective, randomized, multicenter trial; the second was a retrospective review. Children were included in either phase of the study if they had severe egg allergy demonstrated by observation and positive SPT or egg-specific IgE level. Exclusion criteria were incomplete egg-allergy profile, prolonged use of immunosuppressant medications, egg allergy that is resolved, eosinophilic esophagitis, and a history of cardiac disease, active cancer treatment, or pregnancy. The prospective trial started with a questionnaire regarding egg and prior influenza vaccine allergy. Information on SPT and egg-protein–specific IgE was collected from the patients' charts. There were two possible dosing regimens selected by randomization, one by a graded-dosing method (dose was split into 2 aliquots, 30 minutes apart), while the other was a full-dose administration (given at once). The authors blinded these administration methods. Booster doses were given in full if the initial dose was well tolerated. Patients were observed for 30 minutes following immunization and were given a sheet for follow-up for 48 hours afterward.23

The second phase was a retrospective analysis assessing single-dose versus split- dose administration in 112 participants who met the same inclusion/exclusion criteria.23 Patients were enrolled if they had been refused entry into the first phase or if they had received their vaccine dose from their primary physician. Fluzone was used for all immunizations and was reported to have an ovalbumin content of 0.2 mcg/mL (0.1 mcg per 0.5-mL dose). In the prospective phase, 31 participants, 14 to 17 years of age, were assessed for development of an allergic reaction post immunization. There were no anaphylactic reactions in either group, and any adverse effects were independent of the method of administration, whether the vaccine was split into 2 doses or given at once. The authors determined that multidose administration to desensitize patients with egg allergy, as was performed in other clinical trials, is not necessary. This small prospective/retrospective study further documented the safety of the influenza vaccine in children with a confirmed history of egg allergy and questioned the need for a graded-dose approach.23

Des Roches et al: A prospective study of the administration of influenza vaccine to children with egg allergy during the 2010-2011 and 2011-2012 influenza seasons was conducted along with a retrospective review during three previous influenza seasons, 2007 through 2010.12 Allergy to eggs was defined as cutaneous, respiratory, GI, ocular, or cardiovascular symptoms within 60 minutes of egg exposure and was confirmed by an SPT or an egg-specific IgE level. In the prospective arm, the first influenza season included children with egg allergy; however, the second season focused on children with severe allergy, manifested as anaphylaxis or cardiorespiratory symptoms in response to eggs. Following immunization with influenza virus vaccine, patients were monitored for 60 minutes immediately and for 24 hours after immunization. The retrospective study had a similar follow-up period with the information obtained from medical charts. Fluviral, used throughout the study, had an ovalbumin content ranging from 0.03 to 0.31 mcg/mL. There were 367 subjects, 132 with a history of severe egg allergy who received 153 vaccine doses. Thirteen patients reported mild allergic-like reactions within 24 hours of receiving the dose; however, none of the patients developed an anaphylactic reaction.12

The authors did not provide further information on patient demographic data, such as age, or on receipt of first or second dose of the vaccine. There was no further explanation of these “mild” adverse effects; however, it was again encouraging that none of the subjects developed anaphylaxis despite a confirmed history of egg allergy.12

Ovalbumin

James et al suggested a threshold ovalbumin level of <1.2 mcg/mL, below which tolerability to the influenza vaccines would be expected in persons with a history of egg allergy, although no clinical studies have proven this correlation.16 The speculation is that the drop in ovalbumin content in recent years has been responsible for improved tolerance to the influenza vaccines despite documented histories of egg allergy, including anaphylactic reactions.

During the 2009-2010 influenza season, a sample of 35 lots from six of the seasonal vaccines (FluMist, Fluarix, FluLaval, Fluvirin, Fluzone, Influenza HA) was assayed along with a second sample of 23 lots from four manufacturers of the H1N1 vaccine for ovalbumin content.24 The median ovalbumin concentration of the seasonal vaccines was determined to be 0.35 mcg/mL (range 0.0005-1.02 mcg/mL), considerably higher than in the H1N1 vaccine, which was 0.021 mcg/mL.24

Ovalbumin content of influenza vaccines is reported by the CDC yearly and is listed in TABLE 1 for the 2013-2014 influenza season.2 Therefore, knowledge of ovalbumin content in vaccines grown in chick embryos has been proposed to assist in predicting an allergic reaction in a person with a previous egg allergy.2


tbl1

As a result of these studies documenting the relative safety of influenza vaccines grown in chick embryos, the AAP changed the contraindications in children with egg allergy (FIGURE 1).6


Influenza Vaccines That Do Not Include Egg Protein

Until 2013, all influenza vaccines used egg-based technology to grow the virus.2 There are two new trivalent vaccines in which influenza viruses are grown using different technologies, including Flublok, a recombinant HA influenza vaccine (RIV3), and a new cell culture–based influenza vaccine (ccIIV3, Flucelvax).2 Neither vaccine is approved for use in children <18 years old.

A primary advantage of these manufacturing methods is that they might permit more rapid scale-up of vaccine production when needed (e.g., in response to a pandemic). Flublok (Protein Sciences) contains recombinant HA (rHA), and Flucelvax (Novartis) is produced using cell culture technology.2

Flublok: The most current advancement for patients with egg allergy is the availability of the trivalent vaccine Flublok, which was FDA-approved in January 2013 for active immunization against three strains of influenza types A and B antigens in persons aged 18 to 49 years.25,26 The proposed advantage of this product is the novel approach to the manufacturing process, which does not involve the use of eggs.25 Instead, the rHA protein component is produced within insect cells; specifically, the fall armyworm, Spodoptera frugiperda. A baculovirus vector, Autographa californica, is used in this process to produce the HA proteins, which are later purified and prepared for use in the final product. This eliminates the need for inoculating live virus into chicken eggs, thus providing a considerably safer alternative for patients with egg allergy. Flublok-45 contains 45 mcg of each of the three HA antigens in trivalent influenza vaccines (total 135 mcg HA per 0.5-mL dose) and is administered IM.2 Contraindications include severe allergic reaction to vaccine components, excluding eggs. The efficacy and safety of this vaccine have been comparable to other influenza vaccines in adults except subjects >49 years and children <18 years of age.27-30

A randomized, double-blind, multicenter study published in 2009 assessed the safety and efficacy of Flublok in 115 children aged 6 to 35 months and 41 children aged 36 to 59 months.31 Subjects in the younger age group were randomized to receive two doses of either Fluzone (7.5 mcg HA/antigen, 0.25 mL/dose; Sanofi Pasteur); Flublok-22.5 (22.5 mcg rHA/antigen, 0.25 mL/dose, chosen for limits in volume to be injected); or Flublok-45 (45 mcg rHA/antigen, 0.5 mL/dose, chosen for good safety record in adults). Older children were randomized to receive two doses of either Flublok-45 0.5 mL/dose or Fluzone 15 mcg each antigen in a 0.5 mL/dose. Flublok contained A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2), and B/Ohio/01/05–like viruses per 0.5 mL, whereas Fluzone differed in the composition of its influenza B strain (B/Malaysia/2506/04). Both B strains belonged to the B/Victoria lineage. Doses were given IM and separated by 28 days with a 180-day follow-up period. Serum HA-inhibition assay was determined from two blood samples, prior to and 28 days following each immunization to assess the development of antibodies to each of the three influenza strains.31

In the younger age group, seroconversion rates were significantly higher after the second dose of Fluzone as compared to Flublok for all three antigens (P <.0001, .0003, and .0001, for H1N1, H3N2, and B/Ohio/01/05, respectively). These rates were 84% to 100% versus 13% to 58% for Fluzone and Flublok, respectively, for all three influenza strains.31

Although the older age group experienced higher immunogenic responses to Flublok, those remained lower than in patients who received Fluzone.31 Younger patients also experienced more local symptoms with Flublok-45 as compared to Flublok-22.5 or Fluzone, including pain, vomiting, and diarrhea. One child in each of the two age groups who received Flublok-45 developed pain that prevented normal daily activity; however, both cases resolved on their own by the following day. Thus, the investigators determined that Flublok may be as safe as Fluzone in young children, but is less immunogenic and therefore may not be as beneficial as the standard immunization.31

Flucelvax: In November 2012, a trivalent subunit ccIIV3, Flucelvax, was approved in patients ≥18 years of age.32 This vaccine is prepared from virus propagated in Madin-Darby canine kidney (MDCK) cells and contains a total of 45 mcg HA (15 mcg HA of each of influenza A(H1N1), influenza A(H3N2), and influenza B vaccine virus strains) per 0.5 mL single-dose syringe. Egg protein content is very small, 5 × 10-14 mcg/0.5 mL. During manufacturing, Flucelvax is not grown in the chick egg embryo; however, before production, seed viruses are created using reference virus strains that have been passaged in eggs. Therefore, the vaccine cannot be considered egg-free.32 According to the Morbidity and Mortality Weekly Report (MMWR) and studies from the manufacturer, Flucelvax was equally effective as other influenza vaccines in persons aged 18 to 49 years during the 2007-2008 influenza season.2

Summary

Historically, egg allergy had been a contraindication to receiving influenza vaccines grown in chick embryos. This contraindication represented a special concern for children where egg allergy is more prevalent and complications from influenza virus infection are more remarkable than in adults.2 In children with egg allergy, prior recommendations had consisted of referral to an allergist for safe administration of the influenza vaccine in an environment equipped with resuscitation equipment. In this case, a graded-dose administration with close monitoring was recommended. This additional step may have presented a barrier to receiving the vaccine in these patients.

Due to reports of tolerability to the vaccine, the AAP published an algorithm with guidelines for safe administration in children with egg allergy.6 The guidelines stipulate that patients with nonsevere allergic reactions to eggs, such as hives, may be given the influenza vaccines as indicated without splitting the dose, and should be observed for 30 minutes, with similar monitoring recommendations following all other vaccines.

Otherwise, only anaphylaxis or severe reactions to eggs, including cardiovascular changes (e.g., hypotension), GI manifestations (e.g., vomiting), respiratory involvement (e.g., wheezing and throat swelling), or the prior need to use epinephrine for the allergy, were reasons to consult with an allergist prior to vaccine administration. These more strict criteria for allergist referral will hopefully enhance adherence to influenza immunization in many children with milder allergy to eggs who previously were advised to seek referral.

For adults 18 through 49 years of age with a severe or anaphylactic reaction to eggs, the options for influenza vaccine administration have expanded due to the recent availability of two new influenza vaccines. For adults, Flublok presents an alternative to traditional influenza vaccines grown in embryonated eggs. If Flublok is not available, then an allergist referral is recommended. Unfortunately, Flublok has not been shown to be as effective in children as Fluzone.31 Another recently approved trivalent influenza vaccine in adults, Flucelvax has significantly less egg content and should be better tolerated; however, there is still a slight exposure to eggs in the manufacturing process. In the future, we look forward to a recombinant influenza vaccine that will also be effective in children to provide an alternative for the child with severe egg allergy.

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