H1N1 vaccine

Health Care Workers

I believe all health care workers should be immunized against H1N1 and that includes clerks and residents. All health care workers should be immunized annually with seasonal vaccine as well. Healthcare workers have a societal obligation to be available during times of need. The potential large societal benefit outweighs the individual risks.

General Population

Should all of the general population be immunized against H1N1? I am not so categorical here. I understand the position of the Public Health Agency of Canada concerning universal immunization. However, the large majority of illness has not been severe during the first part of this pandemic and a decision to decline immunization is a defendable one. This is certainly true with respect to those above 65 in which there has been very few infections suggesting considerable immunity.

Any risk/benefit analysis is predicate on quantification of risk and this is where things are less clear. The risk associated with this vaccine is undeniably small or it would not have been licensed by multiple national licensing bodies including our own. However, there are legitimate concerns over the level of safety owing to the obvious need for rapid evaluation. The quantification of safety needed for approval was very necessarily less than the level required for vaccines and other drugs that are not needed in as time-sensitive a fashion.

Controversies

The primary safety concerns pertain to the non-viral components of the vaccine as the viral antigens are produced in identical fashion to seasonal influenza vaccines. The Canadian vaccine Arepanrix from GlaxoSmithKline contains the preservative thimerosol and the adjuvant AS03, both of which are somewhat controversial.

Thimerosol
Thimerosol is used in the current vaccine because of the need for multi-dose vials to which adjuvant must be added shortly before administration. It is not practical to add adjuvant one dose at a time. It is a mercury containing preservative that has long been vilified by anti-vaccination groups (especially as a putative cause of autism) and has also been the subject of much study that has vindicated its safety. Despite this large safety data the scepticism persists and the last decade has seen a large reduction in its use especially in childhood vaccines.

My take: Thimerosol is NOT a significant concern.

AS03 Adjuvant
Adjuvants are substances added to vaccines to enhance immunologic response and in the case of H1N1 vaccine are needed to increase the supply of vaccine as much less viral antigen is needed per dose. Arepanrix contains 3.75 micrograms of influenza antigen while Non-adjuvanted vaccine needs 15 micrograms of antigen.

AS03 is one of 2 commercial “new generation” adjuvants that are similar but not identical. The other is MF59 from Novartis for which there is much more experience as it is part of Fluad – a seasonal influenza vaccine that has been widely used in Europe since 1997. The observations of long-term safety pertain to this use of MF59 and are extrapolated to AS03. Both AS03 and MF59 are oil-in-water emulsions containing squalene – a naturally occurring precursor to cholesterol and steroids that is plentiful in shark liver oil, the primary source of commercial squalene (The shark liver origin is the source of fear of problems in people with fish allergy. This is a theoretic problem that has never been reported).

Squalene is particularly controversial in the United States. It was implicated as the cause of “Gulf War Syndrome” when a study of sufferers reported a high incidence of anti-squalene antibodies. Despite much evidence to the contrary and the World Health Organization publishing an extensive report on the safety of squalene containing adjuvants, the US FDA has never approved a squalene-containing adjuvant and the issue may come to a head as H1N1 vaccine shortages loom large in the US.

My take :Early experience with AS03 suggests that is safe and large long-term experience suggests MF59 is very safe. Squalene appears to be a safe component of adjuvants. AS03 has not been used widely and definitive safety information remains to be generated.