POST 00415E : FREEZING AND VACCINE EFFICACY

POST 00415E : FREEZING AND VACCINE EFFICACY Follow-up to Posts 00402E, 00406E and 00407E 21 January 2002 _______________________________________________________________________ Anthony Battersby is concerned about sero-conversion studies to see if frozen vaccines work and wonders how one would set about doing it. It seems to him that it would be unethical to knowingly use frozen vaccines. And if it were found that sero-conversion was inadequate, how would we know that it was due to the vaccine having been frozen or some other factors. Frozen vaccines may still be potent, he adds, but what are the effect of injecting a vaccine with large particles in it. He is not really clear where this suggestion is supposed to lead and wonders if after all these years and all the manufacturers' advice, it is being seriously suggested that frozen vaccine does not matter? He has recently been in a country where reaction to unfrozen DPT (which is normal) was cited as a reason why parents will not allow their children to have two injections at the same time. He imagines that the reaction from lumpy DPT is likely to be greater than the one from homogeneous DPT. Hans Everts disagrees with the moderator's comments in Post 00406E. There is plenty of evidence, he says, that freezing damages the vaccine and changes its morphology. There is very little evidence what the impact is on the immune response. It is surprising to read that "refined knowledge about vaccine efficacy after freezing wouldn't serve any useful operational purpose". The options to prevent freezing range from using eutectics, taking vaccine out of the cold chain, using icepacks with cooled water and changing equipment specifications, all of which have very serious operational consequences. Before recommending changes of cold chain practices at a large scale, we must be certain the risks are worth it. If the changes are in line with what we think the future cold chain looks like or should look like - simplified and with vaccine out of the cold chain - there is of course no objection. But if the changes actually lead to operational and logistics complications or to unaffordable equipment because of refined specifications, then we better be sure they are absolutely necessary. The whole cold chain is based on the fact that a certain loss of potency due to heat exposure is acceptable. That is the basis of the VVM. Hans fully realizes that freezing differs from heat exposure in that it leads to a change in the physical state of the vaccine. The question is if this qualitative leap in the physical state implies the same qualitative leap for the immune response from fully immunogenetic to not at all immunogenetic, or is there a margin. Freezing at -3°C does not have the same effect as at -20°C. Can we afford to ignore this? The former is what we are talking about, related to the current cold chain. The latter implies storage in freezers and is a different issue. _______________________________________________________________ Moderator's comments First let me make a clarification on one point in Post 00412E. The statement on WHO recommendation that reconstituted vaccines be kept on ice was obviously partial and in the context of Anthony Battersby's comments. The primary objective of keeping these vaccines on ice is to protect their potency. But when they have been inadvertently contaminated, keeping them on ice will also slow down the development of the contaminating organism. I share some of Anthony's concerns, not as much for research protocols as for operational implications. This is the basis of Hans' disagreement, I believe. We can all draw our own conclusions from James Cheynes' literature review (Post 00406E). There is a general consensus on the physical/mechanical damage inflicted to vaccines by freezing. However, the five references quoted by James also indicate loss of potency but questions remain about the effect on "protective efficacy". For example in "Vaccine", it is said that there is damage "to immunogenicity of pertussis vaccine ...but that further study is required to determine the effect....on vaccine efficacy". I would then ask the question "Can potency/immunogenicity be damaged without damage to efficacy?" Only one reference quotes a study of the efficacy of frozen tetanus toxoid in vivo on human volunteers. Even if it is said that all persons immunized acquired a protective level of tetanus antitoxin, these "persons" were young military recruits whom I view as the healthiest individuals. Can we infer from this statement that often-sick, often-poorly malnourished children in the developing world will have the same immunological response to a damaged vaccine? I believe that the immune system of such children is weakened. I agree with Hans that freezing at -3°C probably does not have the same effect as at -20°C and that the loss of immunogeniticity is likely gradual. But I meant "operational purpose" only in the hypothesis that there would be no damage to potency whatsoever. Nowhere in the industrialized world, as far as I know, a frozen vaccine with any loss of potency would be used, even a minimal loss. Can you imagine the scandal? The Minister of Health would have to resign in no time at all. I then ask the question "Can we have different moral and ethical standards for children in the developing world?" And if we do find that there is no damage to potency, the loop is complete and we are back to Anthony's question "after all these years and all the manufacturers' advice, it is being seriously suggested that frozen vaccine does not matter?" I also fully agree with Hans about operational implications of all the options to prevent freezing. But these are upstream implications and I was referring to downstream ones after freezing has occurred. ______________________________________________________________________________ ----------------------------------------------------------------------------- All members of the TechNet21 e-Forum are invited to send comments on any posting or to use the forum to raise a new discussion or request technical information in relation to immunization services. Starting in January 2002, TechNet21 e-Forum will have 3 language versions: English, French and Spanish. The comments made in this forum are the sole responsibility of the writers and do not in any way mean that they are endorsed by any of the organizations and agencies to which the authors may belong. ----------------------------------------------------------------------------- CONTRIBUTIONS: Contributions to: or use your reply button! 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