heterosubtypic immunity. My question is: what would be the effect of using an H5N1 or an H5N3 vaccine in the affected areas to induce heterosubtypic immunity, to protect against more severe disease and non-sterilizing immunity? Modeling can look at this in terms of the increased likelihood that an antiviral strategy in a population with partial immunity might affect further spread.

DR. TREANOR: Whether we can induce antibody to neutralize viruses other than the vaccine needs to be evaluated. I question whether an inactivated vaccine can do that, but finding out is critical. We could model a less-than-perfect vaccine and try to figure out how much of an effect it would have.

PROF. FERGUSON: Ira Longini's group has looked at the combination of limited-efficacy vaccines and antivirals. These produce a synergistic impact, and the overall effectiveness of the combined control policy is considerably greater than that of just one measure.

Participant: I agree with Dr. Webster that there are good veterinary vaccines and bad ones. However, I would like to comment on regulatory authority in the U.S. and the European Union, which exerts very strong control of manufacturing of vaccines. The production facilities and quality control of multinational companies such as Meriel Intervet, Lohman Animal Health, and even Biommune are very good, so the quality of the vaccines they manufacture is very high. However, one study Dr. Webster did about six years ago showed that quality control in developing countries without a strong regulatory authority is not very good, so vaccines made there show huge batch-to-batch variation. Some are very bad.

Dr. Webster also showed that veterinary vaccines, especially those for poultry, use a lower antigen content to give optimal immunity and proper protection. Vaccine studies show that the challenge dose has a huge impact on viral reduction and shedding. Thus a poor-quality vaccine used to immunize birds looks very good, but if we give the birds a challenge dose of the same vaccine, the results are not very good. Could Dr. Webster comment on how adjuvanted proteins affected the reassortment of the virus and the challenge virus dose he gave in his duck study?

DR. FINEBERG: Dr. Webster, could you also clarify the term "bad vaccine"? I understood you to mean more than poor manufacturing practice.

DR. WEBSTER: The bad vaccines I was referring to were those made in developing countries without adequate regulation. We see this problem throughout Central America and in China. We need to pay attention to unregulated companies. My message is particularly directed at people from Thailand and Vietnam, who are trying to ensure that vaccines are available when these viruses reappear. Those countries would be very wise to emphasize the quality of vaccines and ask for testing of the batches.

PARTICIPANT: There is an old adage about models: all are wrong, but some are useful. I was happy to see that Neil's model fell into the latter category—that models can help articulate many different assumptions and put them in perspective. One of the key parameters used in your model was the (R0 reproducibility number) of approximately 2, which might well be much greater than 2 if we calculate the reproductive rate based on mortality rates rather than infection rates. Can you comment on the fact that the R0 of a pandemic strain is about 2, while that of epidemic strains is much higher? I thought that influenza is one of the most highly communicative diseases, like measles and varicella.



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