Combination vaccines could be the future of immunisation programs

Childhood immunisation schedules are becoming increasingly crowded, expensive, and unsustainable. Combination vaccines could be the solution.

  • 24 April 2024
  • 6 min read
  • by PATH
A nurse prepares a dose of MenAfriVac during the 2010 vaccine introduction in Burkina Faso. Photo: PATH/Gabe Bienczycki.
A nurse prepares a dose of MenAfriVac during the 2010 vaccine introduction in Burkina Faso. Photo: PATH/Gabe Bienczycki.


Infants in Nigeria are given three separate injectable vaccines at the ages of 14 weeks and 9 months. In the United States, babies may be given up to four injectable vaccines in a single health care visit. Most countries have similarly complex infant immunization regimens.

As more vaccines are developed and recommended for infants, children (and their parents) may be unwilling to handle any more injections during already packed immunization visits. Compounded with many countries' struggles to manage the cost and complexity of storing and administering multiple separate vaccines, combination vaccines seem like an obvious solution.

Yet, few new combinations are in development because, in addition to the scientific and manufacturing hurdles intrinsic to the co-formulation of individual vaccines, they face numerous regulatory, policy, and commercialization obstacles.

A recent health policy paper in The Lancet Global Health posits that national policymakers and public health agencies should prospectively identify and advocate for the development of new multi-pathogen combination vaccines. The authors also propose other tangible, innovative steps to mitigate the current hurdles faced by vaccine developers.

Immunization programs are saturated

Most of the new vaccines recommended by the World Health Organization (WHO) in the last decade have targeted specific high-burden regions and/or high-risk populations, such as dengue fever vaccine and typhoid conjugate vaccines. These, along with a few new vaccines with potentially global attraction (e.g., respiratory syncytial virus, tuberculosis) will increase the number of vaccines for young children in some low- and middle-income countries (LMICs), adding further to the number of injections and vaccination visits that they must bear.

Some infant caregivers, when confronted with the expectation for multiple injections at a single health care visit, may decline a shot or opt to "come back later." Health care provider attitudes towards multiple injections may also affect uptake of recommended vaccines. But a missed or a delayed immunization leaves infants vulnerable to disease, and the deferred visit often will not occur at all in LMICs because of practical difficulties and costs incurred in returning to the health center.

Additional new vaccines for infectious diseases are still urgently needed, particularly in LMICs, and many promising vaccine candidates are in clinical trials. By 2030, there could be vaccines available for up to 30 diseases, with the majority recommended for infants and toddlers.

The pathogens and diseases in bold are targets of WHO's globally recommended vaccines for routine immunization. The rest are recommended for specific contexts, regions, and/or populations or are vaccines in late-stage trials.

"Immunization programs worldwide are struggling with the practicalities of accommodating the growing number of vaccines being recommended and administering them in a limited number of health care visits," said Shabir A. Madhi, PhD, professor of vaccinology at the University of the Witwatersrand in South Africa and one of the co-authors of the policy paper.

"Furthermore, the increasing numbers of individual vaccines that need to be given can be financially prohibitive for many governments, particularly in LMICs," continued Dr. Madhi. "We urgently need to rethink how vaccines are recommended, developed, and delivered, or else we may not be able to maintain current disease prevention levels or successfully prevent additional diseases with new vaccines as they become available."

A call for combination vaccines

Multi-pathogen combination vaccines—that is, more than one vaccine in the same injection to tackle multiple diseases all at once—could dramatically increase adherence to vaccination schedules through easier delivery and greater acceptability from both caregivers and providers. Combinations are also naturally attractive to immunization program decision-makers because they are more convenient to store and transport, and easier, quicker, and cheaper to administer.

PATH's recent value proposition projects on potential Shigella and next-generation rotavirus vaccine candidates queried key stakeholders in a number of LMICs regarding the relative importance of combination vaccine approaches. Both projects included multi-country feasibility and acceptability studies that involved interviewing country-level decision-makers and community health workers about these potential vaccines in Africa, Asia, and Latin America.

"Results from both studies found that the majority of national stakeholders and health care providers in LMICs had a strong preference for combination vaccines, as opposed to adding new standalone vaccines—even those targeting important pathogens—to the immunization schedule," said Bill Hausdorff, PhD, Lead of Public Health Value Propositions and Meningococcal Vaccine Development at PATH's Center for Vaccine Innovation and Access (CVIA) and the lead author of the policy paper.

Despite the potential benefits of combination vaccines and keen interest in this approach from national stakeholders, health care providers, and public health experts, there currently appears to be little commercial appetite to develop them. Only a handful are licensed and being used, with just a few currently in advanced stages of clinical development. This may indicate that vaccine developers perceive that the technical and commercial risks and costs of combination vaccine development outweigh the potential return on investment.

"A congruent and coordinated policy and recommendation apparatus for combination vaccines is currently lacking."

— Bill Hausdorff, Lead, Public Health Value Propositions for CVIA, PATH

Dr. Hausdorff continued: "To better understand these barriers, we convened an independent panel of experts to explore the challenges associated with developing a Shigella-containing combination vaccine, which resulted in broader insights. While overcoming the biochemical and immunological obstacles to combination formulations is certainly necessary, the experts highlighted that addressing strategic, policy, and commercialization obstacles is also critically important. Unfortunately, a congruent and coordinated policy and recommendation apparatus for combination vaccines is currently lacking."

Tangible steps to making more combination vaccines a reality

Given the potential gains to be had from developing new multi-pathogen combination vaccines, it's critical that these barriers are addressed directly and systematically to smooth the pathway for their development and introduction.

The recent policy paper outlines several innovative steps to accelerate the availability of such vaccines. For example, the co-authors advocate for country and regional consultations to identify priority combination vaccine targets and utilization of WHO advisory committees to evaluate combination strategies and priorities. Furthermore, regulatory agencies and health economic evaluations, as well as agencies like Gavi, the Vaccine Alliance, and could give more weight to the overall clinical and programmatic benefit of combinations in their respective assessments versus focusing solely on the clinical effectiveness of each individual component.

"Novel, proactively designed development, regulatory, and policy approaches are needed if we are to successfully deliver many of the vaccines in the current pipeline, and even to help sustain current programs," said Birgitte Giersing, PhD, Team Lead, Vaccine Prioritization and Platforms at the WHO and another co-author of the policy paper.

"We need a paradigm shift in regulatory, policy, and financing perspectives that recognizes the intrinsic value of combinations, and away from considering them as essentially equivalent to the sum of their individual parts," continued Dr. Giersing. "This shift will not be easy. But there may be little choice if we want to continue to rely on vaccine-based approaches to address some of the most significant health challenges of our time."


This article was originally published by PATH on 16 April 2024.