Fewer shots, more protection: The promise of combination vaccines

The last 50 years have seen a dramatic expansion of vaccines available for the prevention of severe and life-threatening childhood diseases. The Expanded Programme on Immunization (EPI), first developed by the World Health Organization (WHO) in the 1970s, began with six essential pediatric vaccines. Today, that number has expanded to 13 universally recommended vaccines, with an additional 17 recommended vaccines depending on country disease burden and risk factors.

There is also a robust pipeline of vaccines in development, meaning the number of recommended vaccines will only increase. This is a major scientific achievement that will prevent more illness and deaths, however, it comes with significant challenges for vaccine delivery systems. And vaccines can only save lives if they are able to be delivered.

Established visits in the childhood immunization schedule are limited, and many already deliver multiple vaccines at the same time.

“We know that it can be challenging to administer multiple vaccines within the same visit. This can actually decrease coverage for vaccines during an established visit if caregivers decide to delay immunizations to prevent multiple shots at once,” says Bill Hausdorff, PhD, Lead of Public Health Value Propositions at PATH’s Center for Vaccine Innovation and Access (CVIA).

Additionally, this lack of capacity within existing visits means that it is extremely challenging to introduce new vaccines currently in the pipeline. Countries are struggling with how to fit even more vaccines in the same number of visits. One clear solution? Combination vaccines.

With a combination vaccine, a single vaccine covers multiple diseases or multiple strains of a disease. This could alleviate these vaccine delivery challenges by introducing vaccines against a broader range of pathogens without increasing the number of separate vaccine administrations.

“The cornerstone of current immunization programs are actually combination vaccines—diphtheria-tetanus-pertussis (DTP)-containing vaccines like pentavalent and hexavalent vaccines, and measles, mumps, rubella (MMR),” notes Bill. “Yet, despite the success of these combinations, few new combination vaccines are in late-stage development especially for young children or maternal immunization.”

Combination vaccines could offer myriad benefits like simpler vaccination schedules, reduced number of shots, easier delivery by health care workers, less cold chain storage, improved vaccine uptake and coverage, and more. But there are major roadblocks that dissuade many manufacturers from investing the significant time and resources required to develop new combination vaccines.

These challenges include a lack of global and regional policies to help prioritize design, development, and use of specific combination vaccines, regulatory hurdles, lack of metrics to value additional vaccine delivery benefits of combination vaccines, and guidance for manufacturers and funders on what combinations country stakeholders want to introduce.

PATH and WHO are taking a multifaceted approach to address these challenges, with the ultimate goal of facilitating the development of new combination vaccines. We are supporting policy development for recommending bodies at national and global levels. Additionally, we are developing health economics metrics to better evaluate combination vaccines and creating a framework to systematically evaluate potential novel combination vaccines, including those identified as priorities by national experts and policymakers.

The framework will evaluate the potential programmatic fit, technical feasibility, and commercial opportunity for novel combination vaccines. Initially, the project will focus on potential combinations that are expected to be used regionally and globally for children younger than 5 years old. This framework is being developed in close collaboration with country-level stakeholders and decision-making bodies to ensure their feedback and priorities are incorporated. Ultimately, the framework is designed to support policy decisions about the introduction and use of combination vaccines.

Furthermore, this week on the sidelines of the Global Vaccine and Immunization Research Forum in Rio, WHO is convening its new Combination Vaccines Technical Advisory Group, which contains experts who will advise on the strategic development of this work. PATH and WHO are also bringing together regulators and developers to discuss the challenging regulatory landscape for combination vaccines. Vaccine regulatory processes and procedures were designed for single-antigen vaccines. They generally don’t consider the overall clinical benefit or delivery advantages that combinations have over standalone vaccines. The goal of this initial meeting is to sensitize regulators to the unique regulatory challenges for combination vaccines and to lay the groundwork for developing solutions.

“We know combination vaccines have real potential to increase vaccine uptake and coverage and can help us incorporate more vaccines into the childhood immunization schedule, ultimately protecting children from more dangerous diseases,” explains Bill. “Our work will hopefully ease some of the barriers that have inhibited combination vaccine development.”