The US government has contracted with at least 5 pharmaceutical manufacturers to develop and produce H1N1 vaccines, using a variety of platforms and manufacturing methods. This is an excellent approach, since at this point no one knows which will succeed and how long it will take to obtain desired quantities of vaccine.
A novel feature of the two H1N1 vaccines being developed by companies Novartis and Glaxo-Smith Kline is the addition of lipid-containing adjuvants to boost immunogenicity and dramatically reduce the amount of viral antigen needed. This translates to much faster production of desired vaccine quantities. UPDATE: The US does not plan to use novel adjuvants in its swine flu vaccines. However, Canada and some other nations do plan to use them. The US will retain its stockpile of approximately 150 million doses of MF59 and ASO3.
Each company has its own proprietary adjuvant, acquired in each case at high cost and intended for the high-stakes business of rapidly producing vaccines for novel pandemics or biological warfare threats.
Novartis’ adjuvant is named MF59, and Glaxo’s is ASO3. We know they work beautifully to strengthen vaccine efficacy. But how safe are they?
That is a very difficult question to answer. Novartis claims MF-59 has been used safely by over 40 million people. However, FDA has not seen fit to approve even a single US vaccine that contains these novel adjuvants.
One European vaccine contains MF59, and two European vaccines contain ASO4, which is a Glaxo adjuvant related to ASO3. Fluad (with MF-59) is only licensed for use in the over-65 population. This age group responds weakly to standard flu vaccines, and whether standard flu vaccines actually reduce flu cases in this age group is controversial. So a stronger vaccine may be indicated for this group. And as we age, we are much less likely to develop autoimmune disorders, so potential autoimmune side effects should also be less in this age group.
However, in the 12 years since Fluad was approved in Italy for older adults (and later in the EU, but not by every country in the EU) no other vaccine containing MF-59 has been licensed… even though MF-59 has been used in a large number of vaccine trials. Virtually all the scientific literature on this adjuvant has been produced by scientists working for the manufacturer, precluding an unbiased assessment of safety at this time.
Glaxo’s ASO4 is used in Fendrix (a Hepatitis B vaccine). Fendrix may only be used for people with end stage kidney disease. Patients on kidney dialysis have a high rate of Hepatitis B infection, and a weak immune system. So they are good candidates for an especially potent vaccine against a disease to which they are highly susceptible, and these recipients are unlikely to develop autoimmune complications.
Cervarix is a vaccine directed against several strains of human papilloma virus (HPV), licensed in both Europe and Australia, which contains ASO4. It is difficult to assess Cervarix‘ safety at this point in time, as data are limited. It is worth noting that FDA has delayed giving Cervarix a US license twice.
The June 19, 2009 Science magazine discusses use of these “next-generation,” antigen-sparing adjuvants for an H1N1 pandemic. It quotes Norman Baylor, director of FDA’s Office of Vaccine Research and Review, who noted that antigen-sparing strategies benefit populations, not individuals. “You have to think about those trade-offs,” Baylor said.