History of vaccine development - the value of combination vaccines

This is the 4980th article of Da Yi Xiao Hu

Nelson Mandela, winner of the 1993 Nobel Peace Prize, once said: Life or death for a young child too often depends on whether he or she is born in a country where vaccines are available or not. This fully illustrates the importance of vaccines to mankind.

Vaccine refers to an auto-immune preparation for preventing infectious diseases that is made by artificially attenuating, inactivating or using genetic engineering methods to prevent and control the occurrence and spread of infectious diseases.

The discovery of vaccines can be regarded as a milestone in the history of human development. In a sense, the history of human reproduction is the history of human struggle against diseases and natural disasters, and vaccination is considered to be the most effective measure to control infectious diseases. This is also proven by the fact that the smallpox virus, which threatened humans for hundreds of years, was completely eliminated after the emergence of the cowpox vaccine, which further convinced people of the role of vaccines in controlling and eliminating infectious diseases.

In 1978, the Ministry of Health issued the "Notice on Strengthening Planned Immunization", and my country officially entered the era of planned immunization. Based on the widespread vaccination of smallpox vaccine in the 1950s and the active promotion of BCG, measles, Japanese encephalitis, and pertussis vaccines in the 1960s (mainly in winter and spring in urban areas), BCG, polio, DTP, and measles vaccines were included in the national immunization program, commonly known as "4 vaccines to prevent 6 diseases". In 2002, hepatitis B vaccine was included in EPI (Expanded Program on Immunization), making the national immunization program "5 vaccines to prevent 7 diseases". In 2007, China once again expanded the national EPI to include hepatitis A vaccine, meningococcal vaccine, measles, rubella, mumps, etc., becoming "14 vaccines to prevent 15 diseases". The implementation of the national immunization program has reduced a large number of avoidable deaths and disease burdens.

With the rapid development of molecular biology, cell biology, medical biotechnology and other related disciplines, new vaccines are constantly being researched and developed, and the types of vaccines have increased significantly. By the end of 2005, my country had produced and used more than 40 kinds of vaccines. The increase in the number of vaccines, while preventing a variety of infectious diseases, is also accompanied by a series of problems, such as an increase in the number of children's vaccinations, increased difficulty in vaccine management, and increased vaccination costs. Therefore, it is imperative to develop and promote the use of a combined vaccine that can prevent multiple diseases.

Combined vaccines are mixed preparations made of two or more live or inactivated organisms or purified antigens, with adjuvants, preservatives, stabilizers, etc., including multi-unit vaccines and multivalent vaccines. Multi-unit vaccines are vaccines that prevent diseases caused by different microorganisms, such as diphtheria, pertussis, tetanus, and tetanus (DTP) vaccines, combined vaccines of diphtheria, pertussis, tetanus, polio, and HIB, combined vaccines of diphtheria, pertussis, tetanus, polio, hepatitis B, and HIB, and measles, mumps, and rubella vaccines. Multivalent vaccines are vaccines that prevent the same disease caused by different subtypes or serotypes, such as 13-valent pneumococcal vaccines, 23-valent pneumococcal vaccines, trivalent influenza vaccines, and quadrivalent influenza vaccines.

The research and development and application of combined vaccines have a history of more than 50 years. The development of diphtheria, tetanus and pertussis (DTP) vaccine was completed for the first time in 1943 and officially launched on the market in 1948. This success laid the foundation for the subsequent development of combined vaccines. The trivalent influenza vaccine in 1915, the octavalent pneumococcal vaccine in 1947, the trivalent inactivated polio vaccine (IPV) in 1955, the trivalent live attenuated polio vaccine (OPV) in 1963, the measles-rubella vaccine (MR) and measles-mumps-rubella vaccine (MMR) in 1971, the quadrivalent meningococcal vaccine in 1978, the diphtheria, pertussis and pertussis and Haemophilus influenzae type b combination vaccine (DTP-Hib) in the 1990s, the Haemophilus influenzae type b (Hib)-acellular diphtheria, pertussis and pertussis (DTP)-inactivated polio (IPV) combination vaccine, and the Haemophilus influenzae type b (Hib)-acellular diphtheria, pertussis and pertussis (DTP)-inactivated polio (IPV)-hepatitis B (HBV) combination vaccine were launched on the market in the 21st century, and the types of combined vaccines are constantly enriched.

"One vaccine can prevent multiple diseases" can bring multiple benefits to children, parents, medical staff and the society. For children, it can reduce the risk of adverse reactions to vaccination, reduce the risk of outpatient crowd gathering and infection, and reduce the number of pain times; for parents, it can reduce emotional anxiety, reduce transportation and work loss costs due to vaccination times, and improve convenience; for medical staff, it can reduce the risk of injection injuries and infection, simplify work processes and improve work efficiency, and reduce vaccine management and storage costs; for society, it can simplify vaccination procedures and improve vaccination coverage and timeliness.

The combination vaccine widely used in vaccination clinics at present is the combination vaccine of Haemophilus influenzae type b (Hib)-acellular diphtheria, pertussis and tetanus (DTP)-inactivated polio (IPV). In terms of production technology, the pentavalent vaccine adopts component purification. Compared with co-purification, the vaccine components of the component purification process are clearly controllable, with high purity, good batch consistency and high stability. In order to reduce the risk of pertussis in infants, WHO recommends that the first dose of DTP vaccine be administered at the earliest 6 weeks of age and no later than 8 weeks of age. The pentavalent vaccine is currently the only vaccine in my country that can be used for vaccination from 2 months of age and contains pertussis components using a component purification process, which can prevent pertussis and other diseases earlier. As a combination vaccine, in addition to preventing pertussis in advance, 1 dose of the pentavalent vaccine is equivalent to vaccinating one dose of "DTP vaccine + polio vaccine + Hib vaccine" at the same time, which can prevent 5 diseases. The use of the pentavalent vaccine to complete the current childhood immunization program in my country only requires 4 injections, which can reduce the number of injections by 8 compared with the traditional vaccination program, bringing multiple benefits to children, parents, medical staff and society.

In 1990, the Global Childhood Immunization Initiative (CVI) proposed that children's vaccines developed in the future should be able to prevent multiple diseases with only one dose of vaccine after birth. China's "Vaccine Management Law" in 2019 also encourages the development of multi-component and multivalent vaccines. Combination vaccines will be the direction of development of vaccination and an inevitable development trend of vaccines in the world and my country.

Author: Zhangzhou Xiangcheng District Center for Disease Control and Prevention

Huang Qiuyan, Chief Pharmacist