The purpose of vaccines is to prevent and/or reduce morbidity and mortality in individuals and interrupt transmission of infectious agents within populations. Vaccines have saved many millions of lives and are forefront in the struggle to contain new emerging diseases including Ebola and Covid-19. Vaccines to ∼25 human viral and bacterial diseases are licensed in the US. On the horizon is the first licensed human vaccine against a eukaryotic pathogen, Plasmodium falciparum, responsible for >98% of deaths from malaria. Vaccine stabilization methods are designed to minimize potency loss during manufacture and losses during storage, distribution, and in-clinic storage/use. Methods vary according to the immunogen, whether an adjuvant is incorporated and anticipated shelf life. Liquid or lyophilized formulations with storage and distribution at 2-8 °C utilize refrigerators that are particularly unreliable, and vaccine efficacy is often compromised. The Ebola vaccine, ERBEVO, is stored/distributed at -60 to -80 °C in specialized freezers or on dry ice, which is even more difficult than 2 to 8 °C. Alternative stabilization methods that maintain adequate vaccine potency at ambient temperatures – increasingly foam drying and spray drying – are used experimentally, but not yet for any licensed vaccines. Eukaryotic whole cell vaccines including PfSPZ Vaccine and several veterinary vaccines (as well as CAR-T and cellular therapies), require cryopreservation with storage and distribution below -150 °C. Little to no loss in potency occurs below Tg, compared to ∼1 log loss over 12 months typical of lyophilized vaccines at 2 to 8 °C. Cryogenic storage is favored for some RNA- and DNA-based vaccines particularly in anticipation of future epidemics requiring long term stockpiling. Cryogenic storage in standard vaccine vials is problematic: these tolerate temperatures down to -80 °C but for CAR-T products and PfSPZ Vaccine new custom cryovials that incorporate a septum for needle access and maintain CCIT at liquid nitrogen temperatures have been developed. And the -150 °C cold chain is more practical than one based on -80 °C or dry ice.
Funding: NIH/NIAID 5SB1AI077262-07 DoD W81XWH18C0326
Conflict of Interest: None to disclose
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