Gelatin is used as a stabilizer in several vaccines. It has been identified as a cause of many anaphylactic reactions to measles, mumps, rubella (MMR), and varicella vaccines [24,25]. A retrospective study that collected sera from individuals who had experienced anaphylaxis after receiving the MMR vaccine found that 27% of them had anti-gelatin IgE, whereas none of the vaccinated subjects who did not experience adverse events had detectable levels of this antibody [26]. Further research has shown that patients who experience anaphylaxis due to the MMR vaccine may also be sensitized to gelatin present in the diphtheria–tetanus–acellular pertussis (DTaP) vaccine [27]. Gelatin is also a source of alpha-gal, a carbohydrate allergen that causes meat allergies. Children with an alpha-gal allergy may experience anaphylaxis after receiving an MMR or varicella vaccine [28].

Thus, children with allergic reactions to gelatin upon ingestion should be evaluated by an allergist before receiving gelatin-containing vaccines. If there is a history of an immediate-type allergic reaction to gelatin, which is confirmed by skin tests or serum-specific IgE antibody tests, it is advisable to test such children for gelatin-containing vaccines prior to administration. If the vaccine skin tests are negative, the vaccine can be administered in the usual manner. However, children should be observed for at least 30 min after vaccine administration. If the vaccine skin tests are positive, the vaccine can be administered in incremental doses under observation [7].

Egg proteins are present in some influenza, MMR, and yellow fever vaccines because they are cultured in chicken embryo fibroblasts or embryonated chicken eggs [10,29]. Egg allergy is common in children, but studies have shown that influenza and MMR vaccines can be safely administered to children with egg allergies [30,31]. In particular, children with egg allergies, including those who experienced anaphylaxis, successfully received yellow fever vaccines without any serious adverse events [32]. According to the ACIP guidelines, individuals with mild egg allergies can receive any licensed age-appropriate influenza vaccine and no longer need to be observed for 30 min after vaccination, as severe allergic reactions to these vaccines are rare [10]. However, individuals with severe egg allergies should only receive influenza vaccines under the supervision of a healthcare provider capable of recognizing and managing serious allergic conditions. For children with egg allergies, the current practice for the yellow fever vaccine is to undergo skin testing before administration. If the vaccine skin test results are negative, the vaccine can be administered in the usual manner. However, the children should be observed for at least 30 min. If the skin test results are positive, the vaccine can be administered safely in graded doses [33].

Casein, a protein found in cow milk, has been implicated in anaphylaxis to DTP-containing vaccines in a small number of children with severe milk allergies [34]. These vaccines are prepared using a medium derived from cow milk protein, and trace amounts of casein are found in these preparations. However, there is no evidence to suggest that DTP vaccines contribute to the development of allergic diseases or that atopy is a contraindication for these vaccines [19].

Thimerosal, aluminum, and phenoxyethanol are added to some vaccines as preservatives. However, thimerosal, which contains mercury, is rarely used as a preservative in vaccines, and its role as an allergen remains unclear [35]. A risk assessment study found no evidence of harm caused by thimerosal in vaccines, except for local hypersensitivity reactions [36]. Additionally, it should be noted that thimerosal is a mercury-based organic compound, and therefore does not possess any toxic characteristics for mammals. These preservatives are not known to cause immediate-type allergic reactions and immediate-type skin testing is not necessary.

Antibiotics, including neomycin, polymyxin B, kanamycin, gentamicin, and streptomycin, can cause allergic reactions ranging from mild to severe, including anaphylaxis. For example, an individual who received the MMR vaccine containing neomycin was reported to have experienced anaphylaxis shortly after vaccination [37]. In addition, one case of anaphylaxis has been reported following the use of eye drops containing polymyxin B, an excipient found in DTaP, and other vaccines [38]. To the best of our knowledge, no other antibiotic has been linked to vaccine-associated anaphylaxis. A commonly used preservative in cosmetics and vaccines is 2-phenoxyethanol. There are favorable reports about this compound for its broad-spectrum antimicrobial activity and good tolerability [10,39].

The use of rubber in vaccine vial stoppers or syringe plungers can cause allergic reactions in some individuals. A report of an anaphylactic reaction following the administration of the hepatitis B vaccine to a latex-allergic patient has been attributed to the rubber in the vaccine stopper [40]. However, a review of 160,000 reports from the Vaccine Adverse Event Reporting System (VAERS) found only 28 cases of possible immediate-type allergic reactions following the administration of a vaccine containing dry natural rubber [41]. Patients with a history of anaphylaxis to latex can safely receive vaccines with non-latex packaging. However, if the only available option contains latex, the vaccine can still be administered. In such cases, the patient must be observed for at least 30 min afterward.

There are relatively few reported instances of anaphylaxis following vaccination in individuals with known allergies to yeast proteins. Between 1990 and 2004, only 15 such cases were reported, 11 of which occurred after administration of the hepatitis B vaccine. This vaccine contained trace amounts of yeast proteins [10]. According to a report from VAERS, 107 adverse events were reported in individuals with a pre-existing yeast allergy. Of them, 11 were probable or possible anaphylactic events following administration of the hepatitis B vaccine [42]. It has been reported that individuals with yeast allergies may experience reactions to vaccines containing yeast proteins. If a patient has a history of reaction to baker’s or brewer’s yeast and has a positive skin test for Saccharomyces cerevisiae, it is recommended to test with yeast-containing vaccines before administration [7,15]. If the vaccine skin test result is negative, the vaccine can be administered as usual, with the patient being observed for at least 30 min. If the vaccine skin test is positive, the vaccine can be administered in incremental doses, with the patient being monitored.

The use of dextran as a medium nutrient or stabilizer in some vaccines, including the MMR vaccine previously used in Italy and Brazil, has been linked to allergic reactions [43]. These reactions were attributed to the presence of IgG antibodies to dextran and activation of the complement system, leading to the release of anaphylatoxins. This brand of MMR vaccine has been removed from the market. However, dextran can still be found in some other vaccines such as rotavirus vaccines.

The Pfizer-BioNTech BNT162B2 and the Moderna mRNA-1273 vaccines are lipid nanoparticles that contain messenger ribonucleic acid (mRNA) coding for the spike protein of the coronavirus [10]. Lipid nanoparticles stabilize and improve the solubility of mRNA vaccines in water and act as adjuvants. These vaccines contain polyethylene glycol (PEG) 2000, a high-molecular-weight version of PEG. This is used as an emulsifier in a variety of products, including vaccines, pharmaceuticals, cosmetics, and foods. PEG and its derivatives are commonly found in household products [10]. There is evidence that sensitivity to PEG may lead to IgE-mediated anaphylaxis after the administration of PEG-conjugated biologics, and severe allergic reactions to PEG have been linked to pre-existing anti-PEG antibodies induced by PEG-containing household products. Although more research is needed to understand the higher rate of anaphylaxis observed with COVID-19 vaccines compared to other vaccines, PEG 2000, a component of mRNA vaccines such as Pfizer-BioNTech BNT162B2 and Moderna mRNA-1273, is considered the most likely cause of allergic reactions. Here, Table 2 shows the components implicated in allergic reactions and related adverse events.