Summary
The Southern Hemisphere influenza season showing H1N1 declining to "normal" levels (WHO release 11 Sep 09
CSL published data on their egg based subunit vaccine with over 90% response rate to the 15 ug (standard) dose.
Accompanying article with similar positive results with adjuvant by Novartis.
If other inactivated vaccines behave the same, there's likely no need for adjuvant or second dose.
Still no firm word on vaccine supply timing.
Analysis
CSL reported in the NEJM their preliminary data on their egg based subunit (inactivated) vaccine in 240 subjects (120 less than 50 years old and 120 between 50 and 64 years old) showing high and acceptable response rates. Details of interest are:
1. Interestingly some 20 to 30% of subjects had baseline titers of 1:40 or greater. Whether this is influenced by circulating H1N1 in the clinical trial site in Adelaide, Australia remains to be seen.
2. Regardless, over 90% of subjects reached what is expected to be protective titers by 21 days after immunization with a single dose. Other data using geometric mean titers and microneutralization are directionally the same and supportive.
3. 15 ug dose was adequate and increasing the dose to 30 ug provides no advantage.
4. There was a trend for lower responses in the higher (50 to 64 yr) age group but not sufficient to consider a different dose (or adjuvant) in that population.
5. These were healthy subjects and this study does not directly address 3 of the 5 priority groups (pregnant women, 24 to 64 with chronic conditions, and children less than 18). One would anticipate that at least for most chronic conditions responses should be similar.
6. Data are directly relevant to 18 to 24 year olds recommended as well as healthcare workers between 18 and 64 without predisposing conditions.
7. The local and systemic side effects were as expected for influenza vaccines and acceptable. This size trial does not address rare side effects, like GBS. That will have to wait until post marketing studies.
8. Importantly, these assays were conducted by the manufacturer and confirmation with data from the NIH studies (due this month) would provide more confidence in the data.
9. It is interesting that in the WHO report influenza reports are slowing back down to "normal" levels in most Southern Hemisphere regions, suggesting that H1N1 will not return as a problem there until their next winter.
Novartis published an accompanying article that showed a single dose of adjuvanted (MF-59) vaccine with only 7.5 ug of HA is likely to be adequate for that vaccine based on immune responses.
However, should NIH studies and other manufacturers (GSK, sanofi-Pasteur) show results without adjuvant similar to CSL then with it looking like a single dose will be adequate it's likely that there will not be a push for use of adjuvant, at least in the US.
It is too early to predict whether the adjuvant vaccine manufacturers (Novartis and GSK) would try to use the adjuvant formulation elsewhere to spare dosing and extend the reach of vaccine.
And no word on whether October delivery is still feasible or what the novel H1N1 season will really look like beyond the college campus outbreaks and the CDC report that over 2/3s of pediatric fatal cases had preexisting conditions, mostly neurological developmental issues. That still means 1/3 (12 cases) did not have such predisposition.
Frank Malinoski consults with leading institutions through GLG
Analyses are solely the work of the authors and have not been edited or endorsed by GLG.
