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Pastimes : SARS - what next? -- Ignore unavailable to you. Want to Upgrade?

To: Maurice Winn who wrote (808)	12/22/2003 8:01:01 PM
From: Henry Niman	Respond to of 1070

The report below uses a fair amount of information from the Feb 20, 2003 FDA Flu Vaccine Meeting whose transcript is at fda.gov This transcript goes over changes in all three viruses in the vaccine, but the Fujian strain is repeatedly brought up and the group eventually votes to wait for additional information. However, the data presented at the meeting are also available online at fda.gov and these data are quite solid on the science side. Eventually the committee reluctantly voted to go with Panama because of difficulties in growing Fujian in eggs and a concern about use of isolates that would grow in eggs after passage through a dog kidney cell line, MDCK. Since a few misconceptions are creeping into the media reports, I thought it would be worthwhile to highlight some of the data in the two documents above. The data for switching to Fujian comes from two sets experiments. One is serological in which ferrets are immunized with various strains, including Fujian, and then the antisera is tested for the ability to neutralize the various known strains as well as recent isolates. A second type of data comes from the actual sequence of the virus' two main surface protein, hemaggluntini (H) and neuraminidase (N). Most of the important data centers on the changes in H. As the viral isolates drift, they can drift away from neutralizing antibodies directed against earlier strains. Thus antisera generated by Panama can be used on new isolates, and those that generate a low titer are cause for concern because the old anti-sera is losing effectiveness. The trend could be seen in tables on page 30 of the above document. The data is dated 2/6/03 and shows data at 6 month intervals for the detection of isolates with low titers against the Panama antisera. The trend is quite obvious as summarized below for each 6 month period ending on the date listed: Sept 2001 5% March 2002 4% Sept 2002 11% March 2003 24% The above numbers are worldwide. Most of the low titer isolates in the latest 6 months had been in Asia (16/38). But the low titer isolates were also beginning to show in the in US (2/21) and Australia/New Zealand/Africa (1/5) This composite data was supported by data on individual isolates as shown on page 28. The most obvious data is located in column I, which has the data for the ferret sera generated against Fujian. The ferrets had a robust titer of 1280 against Fujian, but markedly depressed responses against various earlier isolates including Panama, which was only 40. The other earlier isolates were not much better, with 160 being the highest titer.(against Hong Kong/1550/2002). In contrast, many of the new isolates reacted quite well with the Fujian antisera. Isolates with titers of 1280 or higher included A/Alaska/4/2002, A/Texas/53/2002, A/Hawai/19/2002, A/Beijing/263/2002, A/Hawai/21/2002, A/Massachusetts/01/2003. There were also many isolates from China, Korea, ad Japan with titers of 320 or 640, so it was clear that Fujian-like viruses had already spread around the world, with many of the isolates with the highest Fujian titers coming from the US. In addition there was talk about 2 amino acid changes at positions 155 and 156. These were considered "signature" changes because they were located at one of the neutralization sites, and there was a good correlation between viruses that had these two amino acids changed and high titers against the Fujian antisera as shown on page 29. Five of those isolates (A/California/09/2002, A/Beijing/78/2002, A/Shikawa/2002, A/Osaka-C/70/2002, A/Hawai/290/2002) had changes in both amino acids and all five had titers between 320 and 1280 when tested with the Fujian antisera. However, the viruses had many more mutations than the two "signature" sites. The sequences of A/Panama.2007/99 and A/Fujian/411/2002 have been place on deposit at flu.lanl.gov and a comparison of the twp HA sequences reveals 23 nucleotide differences between Panama and Fujian which lead to 12 amino acid changes (including the 2 mentioned above). 14 of the 23 changes could be seen in mainland china (Ningbo and Zhejiang) isolates from early 2002. Those from late 2002 and early 2003 had all 23 changes mentioned above, and several isolates from early and late 2003 had additional mutations. Thus, Fujian had clearly emerged before the Feb 20, 2003 meeting, and there was little doubt that the science dictated a change in the H3N2 component of the vaccine from Panama to Fujian. In the US, Fujian now accounts for 75-80% of the H3N2 isolates and it is the Fujian strain which is causing much of the fatalities in children and adolescents. Some of this can be seen by looking at the types of mutations that are found in Fujian. Some of these mutations have not been noted since the 1968 pandemic. So many adolescents and young adults are immunologically naive for many of these changes. New flu strain could be harbinger of a pandemic Wily virus able to dodge immune system defenses Sabin Russell, Chronicle Staff Writer Monday, December 22, 2003 ©2003 San Francisco Chronicle \| Feedback \| FAQ URL: sfgate.com/article.cgi?file=/c/a/2003/12/22/MNG563RM8M1.DTL After three of the mildest flu seasons in recent memory, Americans are enduring a major outbreak of influenza that has emptied classrooms and filled hospitals from California to New York. The difference, it appears, is a new strain of the flu virus, known in laboratory circles as A/Fujian/411/2002.

To: Maurice Winn who wrote (808)	12/27/2003 7:39:27 AM
From: Henry Niman	Read Replies (1) \| Respond to of 1070

There now is a fire. I have checked with contacts in Hong Kong, and their colleagues in mainland China have indicated the patient is PCR positive and SARS CoV isolation is being attempted.