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Studies have revealed that vaccines are more often exposed to sub-zero temperatures during cold chain transportation than what was previously known. Such exposure might be detrimental to the potency of temperature-sensitive vaccines. The aim of this study was to evaluate the impact of exposure to freezing on the physicochemical properties and biological activities of recombinant hepatitis E (rHE) vaccine. Changes in rHE vaccine due to freezing temperatures were analyzed with regard to sedimentation rate, antigenicity, and antibody affinity and potency. The freezing temperature of rHE was measured, then rHE vaccine was exposed to freezing temperatures below −10°C.Significant increase of sedimentation rate was noted, according to shake test and massed precipitates. In addition, the binding affinity of rHE vaccine to six specific monoclonal antibodies was significantly reduced and the in vivo potency for eliciting a protective IgG response was also partially lost, especially for anti-HEV neutralizing antibodies. Altogether, our work indicates that exposure of rHE vaccine to a temperature below −10°C results in the loss of structural integrity and biological potency of rHE vaccine.

Accidental exposure of a vaccine containing an aluminum-salt adjuvant to temperatures below 0°C in the cold chain can lead to freeze damage. Our study evaluated the potential for freeze damage in a licensed aluminum-salt-containing protein-D-conjugated pneumococcal vaccine (PHiD-CV; Synflorix, GSK) in conditions that included static storage, single subzero-temperature excursions, and simulated air-freight transportation. Several parameters were assessed including freezing at subzero temperatures, aluminum-salt-particle size, antigen integrity and immunogenicity in the mouse. The suitability of the WHO's shake test for identifying freeze-damaged vaccines was also assessed. During subzero-temperature excursions, the mean temperatures at which PHiD-CV froze (−16.7°C to −18.1°C) appeared unaffected by the type of vaccine container (two-dose or four-dose vial, or single-dose syringe), vaccine batch, rotational agitation, or the rate of temperature decline (−0.5 to −10°C/hour). At constant subzero temperature and in simulated air-freight transportation, the freezing of PHiD-CV appeared to be promoted by vibration. At −5°C, no PHiD-CV sample froze in static storage (>1 month), whereas when subjected to vibration, a minority of samples froze (7/21, 33%) within 18 hours. At −8°C with vibration, nearly all (5/6, 83%) samples froze. In these vibration regimes, the shake test identified most samples that froze (10/12, 93%) except two in the −5°C regime. Nevertheless, PHiD-CV-antigen integrity appeared unaffected by freezing up to −20°C or by vibration. And although aluminum-salt-particle size was increased only by freezing at −20°C, PHiD-CV immunogenicity appeared only marginally affected by freezing at −20°C. Therefore, our study supports the use of the shake test to exclude freeze-damaged PHiD-CV in the field.