Gelatin, an ingredient in vaccines that may induce allergic reactions

In addition to the specific viruses or bacteria and other pathogenic microbial antigens in the vaccine, the ingredients that cause vaccine allergy also include other drugs or added ingredients in the vaccine, mainly including gelatin, antibiotics, preservatives and latex. This time, we will mainly discuss the vaccine allergy caused by gelatin.

Gelatin is produced by the degradation of collagen in connective tissues such as animal skins, bones, tendons and ligaments, and is widely used in the food, pharmaceutical and chemical industries. In order to ensure the survival of viruses or other pathogenic microorganisms as antigens and maintain immunogenicity, gelatin is added to many vaccines as a stabilizer. The gelatin in the vaccine is divided into bovine gelatin and porcine gelatin according to different sources, both of which have strong cross-reactivity. Gelatin levels varied from 15 μg to 15500 μg per dose in different vaccines. Measles, mumps, rubella vaccine and its combined vaccine (MMR), some rabies vaccine and yellow fever vaccine all contain high concentration of gelatin. The commonly used vaccines containing gelatin components in China include live attenuated Japanese encephalitis vaccine, live attenuated combined with mumps vaccine, live attenuated yellow fever vaccine, etc.

Gelatin is the most common component of vaccine-induced allergic reactions, which can induce IgE and non-IgE-mediated allergic reactions. In 1993, Japanese scholar Kelso and his team reported the first case of severe allergic reaction after MMR vaccination due to gelatin allergy. Subsequently, Japan reported that 24 cases containing gelatin-specific IgE antibodies were detected in the serum of 26 patients with severe allergic reaction after MMR vaccination. Allergic reactions to other vaccines have also been reported, including varicella vaccine, yellow fever vaccine, and live attenuated Japanese encephalitis vaccine.

The processing of gelatin has an effect on the sensitization of gelatin. If collagen is hydrolyzed sufficiently, the obtained gelatin has a low molecular weight and low sensitization. In Japan, from 1983 to 1993, children were prescribed to receive MMR at 1 year of age and DPT vaccine (DTaP) at 2 years of age. No MMR allergy was reported during this period. However, in 1994, the regulations were changed to DPT vaccination at the age of 6 months. At the same time, Japanese vaccine manufacturers used natural bovine gelatin with strong sensitization in DPT vaccine. The incidence of MMR vaccine allergy increased significantly, and most patients with severe allergic reactions (93%) and some urticaria-like reactions (56%) were found to be gelatin-specific IgE positive. Since 1999, the gelatin component has been removed from the DPT vaccine produced in Japan, and the gelatin component has been removed from a variety of virus live vaccines since 2000. The incidence of vaccine allergy has decreased significantly.

Gelatin has been shown to be one of the main causes of vaccine-induced allergies. Since 2010, the State Food and Drug Administration has made it clear that for high-risk grade excipients such as gelatin, the formula of freeze-dried protectant should be screened in the early stage of product development, the necessity of using gelatin in this product should be evaluated, and other freeze-dried protectants should be used as substitutes as far as possible.

Chengda Libao^®High-density microcarrier cell culture technology was used in the upstream of inactivated Japanese encephalitis vaccine (Vero cells) to harvest high-titer antigen. The four-column serial chromatography purification system was adopted downstream, and the purification efficiency was 99.95%, which effectively removed the impurities in the vaccine.Formaldehyde, antibiotics and gelatin are not added throughout the production process.Reduce the incidence of adverse reactions after vaccination. The first Japanese encephalitis vaccine liquid dosage form does not add preservatives. The residual amount of bovine serum was significantly better than the national pharmacopoeia standard. The safety index is better than domestic and international similar products.

References:

Meng Juan, etc. Vaccination management strategy for children with drug allergy history [J]. Chinese Journal of Clinical Immunology and Allergy, 2020,14(6):592-598.

Liu Zhilei, et al. Thoughts and Suggestions on Gelatin Removal of Live Attenuated Viral Vaccines [J]. Chinese Journal of Biologics, 2018,31(11):1286-1289.