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John R. La Montagne Memorial Symposium on Pandemic Influenza Research: Meeting Proceedings
Many people have thought about doing that, but it’s a very costly exercise, and nobody has tried it. Such a study requires a considerable number of non-human primates as well as a better understanding of the infectious dose.
DR. GERBERDING: It is not so much science as samples that are rate-limiting.
DR. FINEBERG: The second question concerned intradermal immunization or route of administration more generally.
DR. FAUCI: Yes, I agree with you completely. If we consider whether we could stretch out supply, and give a half a dose intradermally versus the full dose intramuscularly, we could prove the concept that we could get relatively equivalent protection. Another question is: what happens if you give an equivalent dose intradermally to intramuscularly in elderly individuals who generally have poorer antibody response? I would be interested, from an immunological standpoint, as to whether we can boost the relatively poor immunological response in people 65 years of age and older toward a relatively normal response by using intradermal dosing but relying on the dose that we would use intramuscularly.
DR. FINEBERG: If I understood, your point was also that the immunologic memory might enhance responsiveness to an intradermal dose of lower intensity, and therefore could mask what might happen in a population that was immunologically naive.
DR. GELLIN: Both those questions highlight the need for international collaboration. Dr. Stohr, I hope you hold the meeting you mentioned, because based on what we have seen here, I think there is going to be tremendous interest. If we continue to compare apples to oranges we are going to be in trouble, because we are going to have a range of data points that we don’t know how to put together. We need international collaboration to understand who is doing these studies and how they are advance the science in this area.
PARTICIPANT: In response to the previous question about the apples and oranges of intradermal versus subcutaneous: In preparing for tomorrow’s workshop, I found a number of studies that used the same dose intradermally and subcutaneously.
Back in 1949, Bruin et al. found that, using the same doses, geometric mean titers were higher intradermally than subcutaneously in both adults and children. Still, when the antigen mask was small, intradermal did better. When the antigen dose quantity was higher, subcutaneous did better. More recently, in 1969 in the Canadian Journal of Public Health, Davies found that giving the same dose intradermally or subcutaneously with jet injectors for both routes produced a higher response intradermally, but the result was not significant.
PARTICIPANT: Our biotech company, founded less than two years ago under the National Biodefense Program, focuses on developing novel therapeutics and prophylaxis for influenza. I agree that a fundamentally new approach against influenza is greatly needed, because as Dr. Fauci pointed out, even cross-reactive vaccines are very difficult to generate because the natural infection doesn’t offer long-lasting cross-protection. In light of this, we have developed a new molecule that is sialidase based and is designed to tether to the human receptor epithelium. Our lead works by eliminating the sialic acid used as a receptor for all strains of influenza viruses. The strain works by making the host inaccessible to influenza viruses. With the help of NIAID, we have done some very successful in vitro studies, and now multiple animal studies, showing that this approach holds great promise, not only as a prophylaxis but as a