Background

Combination vaccines (including polyvalent vaccines) are formulated by combining two or more different pathogen-associated antigens with adjuvants, preservatives, stabilizers, etc. There are two main types of combination vaccines: 1) the first category composes of antigens from different pathogens and can simultaneously prevent diseases caused by multiple pathogens; 2) the second category (polyvalent vaccines) combines different subtypes or serotypes of the same pathogen, which can prevent diseases caused by different antigens of the same pathogen and have a broader risk prevention effect.

With the increase in vaccine types, promoting combination vaccines that can simultaneously prevent multiple diseases has become a global trend. They can reduce the pain of recipients and the workload of vaccination personnel and optimize the utilization of health system resources, providing innovative impetus for research and development institutions. Most studies have confirmed that combination vaccines have immunogenicity and safety equivalent to monovalent vaccines. The World Health Organization has been advocating for the use of combination vaccines to reduce the number of doses administered. Many countries worldwide have included pentavalent and hexavalent vaccines in their immunization plans, and China’s Vaccine Administration Law also explicitly supports the development of new combination vaccines. However, the coverage of combination vaccines among children in China is still insufficient, and the challenges of one child receiving multiple doses of vaccines are prominent.

Methods of evidence collection

The team members searched the existing Chinese and English literature databases (such as PubMed, Wanfang, CNKI, etc.), original databases (including Global Burden of Disease, WHO Immunization Data Portal), gray literature from the Internet, research reports of international organizations, position documents and policy articles. The team members used combination vaccines, quadrivalent vaccines, pentavalent vaccines, and hexavalent vaccines, as well as specific disease names as search keywords. Based on high-quality research and evidence, they extracted key information related to the areas of concern and major domestic and foreign research and comprehensively organized and integrated the information to form the “Practice and Scientific Basis” report.

This evidence pool summarizes the main research findings on pediatric combination vaccines, covering the burden of common vaccine-preventable disease (VPD) among children. It focuses on the advantages, immunogenicity, and safety of combination vaccines for children and summarizes the application experience for children in certain developed and developing countries. The aim is to provide a solid foundation for policymaking and health education activities to optimize immunization programs, improve combination vaccine coverage, and promote population health.

Main findings

The main findings of the report are as follows:

• Diseases burden of VPDs among children

The ten VPDs included in this report are mostly highly contagious and may cause serious infections, posing significant health risks to infants and young children worldwide. In China, the incidence rates of whooping cough, mumps, and hepatitis B virus-related diseases are significantly higher than the global average, while cases of varicella, Haemophilus influenzae type b(Hib) infections and other diseases are increasing annually.

• Combination vaccines for children can benefit recipients, caregivers, healthcare workers, national public health systems, and the R&D institutions

A series of cost-effectiveness and social outcomes studies related to combination vaccines for children have been conducted domestically and internationally, and the research provides strong evidence supporting the promotion of combination vaccines for children. For recipients, combination vaccines can improve vaccination compliance and timeliness, reduce vaccination frequency, and minimize discomfort; for caregivers, direct medical, non-medical, and indirect social costs will be reduced; for medical personnel, the workload and injection-related risks will be reduced, and efficiency will improve; for the national public health system, combination vaccines can reduce logistics costs and optimize the immunization programs. In addition, companies may be motivated by R&D and innovation to develop combination vaccines.

• Most quadrivalent, pentavalent, and hexavalent vaccines have immunogenicity and safety equivalent to monovalent or lower valent vaccines

The application of highly effective combination vaccines is one of the most cost-effective means to reduce incidence and mortality among children. Several types of quadrivalent, pentavalent, and hexavalent vaccines have been approved. Clinical trials and real-world evidence conducted in different countries have confirmed that higher-valent vaccines developed based on pertussis, diphtheria, and tetanus (DPT) vaccines have immunogenicity and safety equivalent to monovalent or lower-valent vaccines. However, quadrivalent vaccines based on the measles, mumps, and rubella (MMR) vaccine may lead to a slightly higher incidence of fever, seizures, and pain after the vaccination.

• Combination vaccines for children are widely used in many countries with high coverage and low costs and are covered by medical insurance.

In most developed countries, combination vaccines for children have been included in national immunization programs and are covered by national medical insurance or public health programs. The coverage rates are close to or over 90%. In some developing countries supported by the Global Alliance for Vaccines and Immunization (Gavi), combination vaccine coverage has also reached around 80%.

• The promotion of pediatric combination vaccines in China faces slow progress. hindered by barriers related to the immunization system, policy making, R&D, vaccine hesitancy, etc.  Advocating on evidence-based decision-making requires further studies to fill the evidence gaps.

By summarizing the development and coverage status of combination vaccines in China, we identified several challenges:) insufficient R&D capabilities, 2) high vaccine costs, and 3) low vaccination rates. It is also essential to solve the schedule conflicts with the existing national immunization program vaccines, optimize incentive policies, encourage the industry for joint R&D, increase vaccine awareness and acceptance, and address the evidence gap for evidence-based decision-making.

Content Editor: Siqi Jin

Page Editor: Ziqi Liu