Exquisite Science
Matthew Pennington

COVID-19 Vaccine Distribution— A 'Chilling' Challenge

The novel RNA vaccines need to be stored in very cold temperatures. How will public health manage this?

 In every biology class’s introduction to vaccines lesson, students learn that an ideal vaccine should be:

1. Effective at preventing infection and conferring long-lasting immunity against a range microbes (multivalent)
2. Safe, with no serious side effects
3. Inexpensive to produce
4. Easy to administer, ideally only requiring one dose, and
5. Thermally stable

This last point may be overlooked by many, but proper vaccine storage and handling are critical factors in preventing and eradicating many common vaccine-preventable diseases. It is also one of the hardest hurdles to overcome in the widespread distribution of any vaccine. Vaccines are like any food— if left at the wrong temperature they will spoil and become useless. Poorly handled vaccines, if given, can result in patients not developing proper immunity, needing to receive additional vaccines, and losing confidence in vaccination and their doctors.

 A cold chain has been developed to ensure that vaccines are kept at the appropriate temperature, beginning with their production, continuing through shipment, and ending when it is delivered to the patient. All routine vaccines widely distributed worldwide need to be stored at either 2 to 8°C (36 to 46°F, refrigerator temperature) or at -15 to -50°C (-58 to 5°F, a household freezer is around 0°F). Both the US Centers for Disease Control and World Health Organization have extensive recommendations for best practices to maintain these temperatures.

 However, the cold chain has received renewed focus in recent months due to the logistical challenges of distributing an eventual COVID-19 vaccine. The two leading candidates are mRNA based, a new technology that appears to be highly effective. However, one of these must be stored at -70°C (-94°F, colder than Antarctica), or the RNA molecules will quickly break down. As no other routine vaccine needs to be kept this cold, most doctors’ offices, pharmacies, and other locations where a vaccine might be distributed do not have freezers capable of keeping the vaccine this cold. These specialized, ultra-cold freezers are typically only available at large medical centers, are expensive to obtain and operate, and are currently in short supply.

 A storage container with dry ice has been developed and can keep the vaccine cold for 10 days, but this timeframe includes both shipping and distribution. Fresh dry ice can be added to extend storage for 5-15 additional days and the vaccine can be stored for 5 days in the fridge. This gives a maximum of 30 days, but more realistically less, to distribute all of the doses in the container. Each box can hold 1,000-5,000 doses. However, in order to maintain temperatures, these boxes can only be opened twice per day, for a maximum of 3 minutes each. Only large distribution centers are likely to be able to quickly and effectively utilize all of these doses.

 This means that many people, especially in more rural areas, may need to travel significant distances to get a vaccine as it is simply not effective to bring these boxes to small communities. Considering the mRNA vaccines are expected to require two doses, this may further reduce the number of people who are properly vaccinated. More vaccines are in the developmental pipeline which do not need to stored at these ultra-cold temperatures, but those require more testing before they are approved.

 This also raises long-standing concerns regarding equitable vaccine access. The WHO Global Vaccine Action Plan, developed in 2012, made recommendations to ensure that all children receive access to vaccines. We have not been able to live up to this plan, with only 86% of children worldwide receiving necessary vaccinations in 2018. The cold chain considerations of a COVID-19 vaccine will likely only exacerbate this disparity.

 As COVID-19 vaccines are nearing approval, no matter which vaccine is approved first, key attention must be taken by public health officials to develop both plans and new technologies to ensure that those in rural and medical-underserved communities, as well as those in developing countries, have equal access to vaccination. Scientists were able to beat the odds and develop these revolutionary vaccines in record time. Now it is up to them again, working closely with public health officials, to find solutions to these distribution challenges to transform this good vaccine into an ideal vaccine.