R21 Vaccine Cost Estimates

Estimating the cost of delivering the R21/Matrix-M malaria vaccine

Author: David Tellett

R21 vaccination: Costs and comparisons

At the end of 2023, the WHO approved the use of the R21/Matrix-M malaria vaccine as a low cost option offering a good level of protection for millions of children under the age of 5 at risk for malaria. In their initial recommendation, they suggested that, at prices of $2 – $4 US per dose, the cost-effectiveness of the R21 vaccine would be comparable with other recommended malaria interventions and other childhood vaccines.¹

Estimating the full cost of delivery of a vaccine program is complex. Program design and logistical costs will vary significantly between countries, and as R21 is a new vaccine there is limited data available. However, based on analysis of distribution costs for the RTS,S malaria vaccine and the current per-dose cost of R21, 1DaySooner estimates that fully vaccinating children could cost as little as $25 per full course (four doses total) in early years, with prices likely to decrease as vaccination campaigns scale. This cost is in line with a 2013 study which found an average cost per child of $23 (2013 dollars) for other new vaccination programs in LMICs.²

Purchase price per dose

UNICEF has secured its initial allocation of R21 doses at a price of $3.90 each, with prices scheduled to fall based on volume.³ This is comparable in price to a number of relatively new vaccines, including routine immunizations such as the MMR vaccine and recently rolled out pneumococcal conjugate (PCV) vaccines.⁴

Prices per dose negotiated by UNICEF range from $0.15 for the BCG, a tuberculosis vaccine developed over 100 years ago, to $98.60 for an effective newly-developed Ebola vaccine which, due to its high cost, is used primarily as an emergency option in regions at risk from outbreaks. Some selected examples:⁵

DTP-HepB-Hib (6 in 1): $0.83-$1.24
Hepatitis A: $6.99
Influenza (Quadrivalent variants NH/SH): $4.40-$5.70
Malaria (RTS,S): €9.30 (~$10.00)
Malaria (R21): $3.90
MMR: $1.71-$4.47
PCV10: $2.00-$2.90
PCV13: $2.75-$3.30

(Prices above are 2023 prices as negotiated by UNICEF for Gavi, and exclude higher prices negotiated for middle income countries. Price ranges per dose represent costs of different presentations of the drug.)

Most developing countries purchasing the vaccine will pay less than the negotiated purchase price due to subsidies from the foreign aid and donor-supported Gavi. The Gavi subsidy reduces the price of both RTS,S and R21 to $0.20 for the poorest countries. This is one reason why the WHO considers the cost of local programs for R21 to be roughly equivalent to those of RTS,S, despite the latter costing more than twice as much. For countries eligible for the highest level of Gavi funding, the majority of the cost of the vaccine program incurred by these countries’ governments is the cost of delivering the vaccine, not the vaccine itself.

In addition to the vaccine price, the overall cost of a vaccine program includes financial costs associated with delivering the program including transport and capital investment in new resources like cold chain storage, and the opportunity costs of using resources like staff time and existing cold chain storage capacity. Costs vary significantly between countries, with the largest contributor to the difference in costs of delivery between different countries being the cost of local labor.

Cost of delivery

Not all of these costs are recurring. Much of the overall cost of introducing new vaccines is time that must be invested in planning rollouts, organizing logistics and training staff, and some vaccinations require additional capital investment in cold chain storage. Similarly, not all of these costs represent an increase to the government budget: the overall economic costs of vaccination include the opportunity cost of using existing resources like salaried staff to deliver vaccinations.

The net economic cost of a RTS,S and R21 vaccination program will be lower, as cost estimates factor in the economic cost of using existing healthcare resources to deliver vaccinations, but not the effect of a reduction in cases of clinical malaria in vaccinated children on resources used to diagnose and treat malaria.

A (highly simplified) overview of the different types of costs that must be estimated is included below:

Differences in costs included and assumptions made make comparisons between studies of other vaccine delivery costs difficult.⁷ A 2018 study incorporating data from vaccine rollout programs between 2009 and 2018 estimated a typical programmatic economic cost per dose across all vaccines was $1.41 ($0.52–3.16) for low income countries and $1.36 ($0.44–3.32) for lower middle income countries.⁸ Another literature review found an average cost of delivery of $1.68 per dose across the GAVI-supported LMIC countries.⁹

R21 is straightforward to deliver, does not have particularly onerous storage requirements, and initial doses can be delivered alongside existing EPI immunization programs to the same age group, so the WHO expects the cost of delivery to fall within a similar range. The most obvious point for comparison with available data is the RTS,S trial program, as both R21 and RTS,S involve a course of three injections followed by a booster injection the following year. Analysis of the RTS,S pilot in three countries estimated economic costs of between $1.52 and $4.62 per dose for introduction within routine immunization programs. This included the time local healthcare workers spent on the program and direct financial costs of between $1.04 and $2.46 per dose. Excluding substantial one-off startup costs, the recurring economic cost of distribution was between $0.59 and $2.29 (financial costs between $0.29 and $0.89) per dose.¹⁰ Estimates for RTS,S rollout to other priority countries for malaria vaccination were similar.¹¹ R21 may cost a little less to distribute than RTS,S as it has less strict cold chain requirements and a dose is supplied in a single vial, potentially reducing transit and storage costs, wastage, and even staff time.

Routine vs. seasonal vaccination schedules

As the rate of malaria infections is seasonal in many countries, the trials for R21 (and RTS,S) compared options where immunization schedules were optimized for the seasonal variation in malaria infections, and options where they were optimized for vaccination alongside existing child vaccination programmes. The benefit to optimizing immunization schedules for seasonal malaria was statistically significant, but not huge.¹² ¹³

Optimizing vaccination schedules for malaria seasons is the one major factor which could increase the costs of delivery above regular EPI programs. One study suggested that the economic cost of delivering RTS,S in Burkina Faso could be $0.48 per vaccination alongside existing EPI immunizations, but $1.17 if they were to organize a mass campaign to ensure unvaccinated infants all received their vaccine course at the optimal time for the malaria season.¹⁴ Developing countries with seasonal malaria face a difficult choice between the most effective and the lowest cost R21 immunization programs. Governments rolling out programs will also have to consider whether to invest additional resources in outreach to vaccinate under 5s who have already received other routine immunizations.

Conclusion

There are many areas of uncertainty in estimating the cost of delivering vaccines in different countries. Distribution costs are highly variable between countries, and will likely be higher where states use additional resources to maximize coverage or optimize vaccination schedules for peak malaria season. There are wide differences in salaries and logistics between different countries. Exchange rates fluctuate and labor costs may rise in future. Lastly, as many of the vaccine programme costs are fixed, the ultimate cost per dose and cost per fully vaccinated child will depend upon the vaccine uptake.

That being said, there is no reason to believe that R21 will be a particularly expensive vaccine to deliver. Based on the RTS,S pilot data and $3.90 price ceiling for the vaccine, R21 could be delivered for an all-inclusive initial cost of less than $5.50 per dose in some countries.¹⁵ Recurring costs would be in the range $4.49-$6.19 per dose,¹⁶ and potentially lower if the vaccine price falls as expected.

Ultimately what matters most is the outcomes. Vaccinating 1 million children in 2024 at $5.50 per dose would cost $25 million (including the subsequent 2025 booster) and save an estimated 6,320 children from death by malaria¹⁷ — about $3,956 per life saved. These costs could be further reduced in future years with prices set to fall based on volume, and one-off startup costs already paid. And as discussed in the Cost of Delivery section, whilst delivering the vaccines to that many children costs a significant amount of healthcare professionals’ time, by reducing the incidence of clinical malaria in under 5s by over 40%,¹⁸ it significantly reduces the resource costs of treating symptoms and so net costs will be lower still.

With a projected cost of less than $4,000 per life saved initially, and less than $3,000 per life saved in the long run, R21 is expected to be a highly affordable way to reduce the number of lives claimed by one of the world’s deadliest diseases.