Dear Colleagues,
PATH is pleased to share with you key findings on the technical and commercial feasibility of stabilizing vaccines. These findings are outlined in a recent guest editorial published in the journal Human Vaccines.
In the editorial, PATH's Debra Kristensen, group leader of Vaccine Technologies, and Dexiang Chen, senior technical officer, reflect on nearly eight years of work with 33 collaborators to optimize the heat- and freeze-stability of seven vaccines. They also suggest the following recommendations for developing and commercializing vaccines with enhanced temperature stability:
• Stabilization efforts should be integrated into early vaccine development.
• There are circumstances where it makes sense to stabilize existing vaccines.
• Freeze stabilization is possible for vaccines containing aluminum adjuvant.
• Heat stabilization requires a customized approach, and results will be variable.
• The full benefits of heat-stable vaccines will only be realized after programmatic and policy changes are made to storage guidelines.
• Improvements in vaccine heat stability are inextricably tied to product format, and careful consideration should be given to the end-product attributes and priorities during vaccine development. Some heat-stability improvements result in inferior product formats while others enable new, beneficial formats.
• Products with enhanced stability can benefit both vaccine producers and purchasers.
For more information on PATH's work in vaccine stabilization, please visit: http://www.path.org/projects/vaccine-stabilization.php
Thank you,
Amy Wales
PATH
Dear Moderator,
The report is very informative, greetings to PATH for this.
Omesh Bharti
Dear Moderator,Thanks for the report.I have 2 questions:
- If a freeze sensitive vaccine is used after it was frozen, is there any AEFI besides it being less potent?If there is no adjuvant (in the vaccine), such as Sanofi’s H1N1 liquid 10-dose vaccine, then why are we afraid of freezing?
Dear Faisal:
I will try to answer your questions.
Re: Effects of vaccine freezing
Decreased vaccine potency is the main concern following vaccine freezing. It is also possible that freezing a vaccine with aluminum adjuvant could increase local reactions at the injection site. There are few published data on this topic, however. The best I could find is posted below:
"Sterile abscesses are rare (~1 per 100 000 doses) local reactions from aluminum containing vaccines, especially DTP. Inadequate shaking of the vaccine before use, superficial injection, and use of frozen vaccine increase the risk of sterile abscess and of local reactions."
From: ADVERSE EVENTS FOLLOWING IMMUNIZATION (AEFIS) (Immunization Safety Surveillance, WPRO/EPI/99.01, 1999)
http://www.wpro.who.int/internet/files/pub/116/9.pdf
Re: Freeze-sensitive vaccines without aluminum adjuvant
Some vaccine antigens (such as H1N1) can be damaged by freezing. The cause of the damage could be due to aggregation, inactivation (live vaccines), or degradation of the antigen—all of which can result from vaccine freezing.
All the best,
Debbie Kristensen
Dear Debbie
Thanks for such a wonderful response.One quick question:Freezing has no effect on polio vaccine which contains live antigens, why?Best regards,Faisal Mansoor
Dear Faisal
You raise a very good point. Studies have shown that live oral polio vaccine can be subjected to repeated freeze thaw cycles without a loss of potency (for an example, see WHO Weekly epidemiological record, 1990, 65: 207-210). However, a critical point in this study was that the 'high' temperature was still within the range of a working refrigerator (in the case of the study cited, this was +2.1 C).
Exactly why live OPV is resistant to damage by freezing is less clear. Current formulations of OPV contain stabilizers, usually a high concentration of magnesium chloride. Divalent cations such as Mg++ bind to proteins and stabilize their structure. This could presumably explain the protection against freezing. Magnesium chloride also lowers the freezing point of the vaccine to -6 to -8 C.
I hope this is useful.
Kind regards
Julian Hickling
Basically the water content of the live cell gets to crystalize and vice versa due to freezing and thawing. That actually causes cell disruption and once the cell dies, it behaves as a killed vaccine. But subsequent to the death of the cell, the RNAs and other enzymes becomes active at a higher temperature and helps in distroying the cell. However, in a freeze dired vaccine, the freeze drying proces removes the water content of the cell (Pl. note it all happens at molecular level since we are addressing the issue of a cell). The cell regains its originality once it is reconstituted. So usually nothing happens to the live cell which was in a freeze dried condition earlier. No protein degradation occurs. Nagaraj
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