The core function of a vaccine is to trigger immune responses that specifically target a particular pathogen. Historically, vaccines were designed, developed, registered, recommended, procured, and administered as monopathogen formulations. However, the control and elimination of numerous diseases were only achieved after several previously separate vaccines were combined into single formulations.
Combination vaccines are numerous, with the measles-mumps-rubella (MMR) and diphtheria-tetanus-pertussis (DTP or DTaP) vaccines being among the most common. However, various other tetravalent, pentavalent, and hexavalent vaccines, which include DTP/DTaP alongside additional components such as Haemophilus influenzae type b (Hib), hepatitis B, inactivated polio vaccine (IPV), varicella, and others, are also used in different regions.
Additionally, combination vaccines for respiratory viruses, including influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), are expected to become available soon, as the development pipelines show great promise.
Finally, it is important to highlight combination vaccines targeting multiple serotypes of a single pathogen, such as multivalent pneumococcal and meningococcal vaccines.
Potential Value of Combination Vaccines vs. Coadministration of Separate Antigens
Vaccine Delivery
Potential Advantages
- Improved timeliness of vaccination, with greater acceptance from both end users and healthcare providers.
- Higher and more equitable vaccination coverage.
Potential Challenges
- Ensuring compatibility between vaccination schedules and administration routes for each component.
Health Impact
Potential Advantages
- Greater and more equitable health impact.
- Enables targeting of less prevalent but still significant pathogens.
- Provides the possibility of a syndromic combination—targeting pathogens that cause the same clinical syndrome.
Potential Challenges
- Demonstrating the incremental health and economic benefits of the combination compared to standalone components.
- More challenging to attribute safety signals to a specific component.
Vaccine Administration Efficiency and Cost
Potential Advantages
- Fewer syringes and reduced packaging disposal need.
- Less cold-chain storage and transportation space are required.
- Shorter administration time, with fewer errors.
- Reduced number of needlestick injuries, improving safety for vaccinators.
Potential Challenges
- Combination vaccines could be more expensive to procure than individual components, despite potentially lower delivery costs.
- Some available combinations may contain more vaccines than countries are willing to introduce.
Vaccine Design, Development, and Supply
Potential Advantages
- Greater demand for combination vaccines than for individual components, potentially leading to economies of scale and reduced cost of goods.
Potential Challenges
- Lack of guidance or recommendations from the public health community regarding combination composition or usage preferences.
- Higher risk of failure due to immunological interference or unacceptable reactogenicity.
- A more complex, lengthy, and costly clinical development pathway, driven by current regulatory guidelines.
- Need to develop and validate additional assays to accurately characterize components within complex mixtures.
- Limited competition if only a few developers have access to all necessary components or must engage in complex intellectual property agreements.
- Without guidance on preferred combinations, the market could become fragmented, resulting in numerous competing, overlapping, and commercially unviable combinations, ultimately increasing costs.
Conclusions
In July 2024, the World Health Organization (WHO) published a call for experts to join the WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC).
While there are numerous challenges, the benefits of investing in the manufacturing and implementation of combination vaccines far outweigh those of using monopathogen vaccine deliveries. This approach offers significant advantages for both developed and developing countries, leading to substantial, long-term benefits.
References
- Hausdorff WP, et al. Facilitating the development of urgently required combination vaccines. The Lancet Global Health 2024; 12(6): e1059 – e1067. 10.1016/S2214-109X(24)00092-5.
- Call for experts: WHO Technical Advisory Group on COVID-19 Vaccine Composition 2024. https://www.who.int/news-room/articles-detail/call-for-experts-who-technical-advisory-group-on-covid-19-vaccine-composition-2024.
- WHO. Immunization Agenda 2030: A Global Strategy to Leave No One Behind. https://www.who.int/teams/immunization-vaccines-and-biologicals/strategies/ia2030.
- Watts E, et al. Economic benefits of immunization for 10 pathogens in 94 low- and middle-income countries from 2011 to 2030 using cost-of-illness and value-of-statistical-life approaches. Value Health. 2021; 24:78-85. 10.1016/j.jval.2020.07.009.
- Maman K, et al. The value of childhood combination vaccines: from beliefs to evidence. Hum Vaccin Immunother. 2015; 11:2132-2141. 10.1080/21645515.2015.1044180.
