Question: Now that FDA has approved use of H1N1 vaccines from manufacturers, what do the different products contain in regards to the adjuvants for immune stimulation? Are there potential risks? Is this information readily available?
Answer: At this point, FDA has approved vaccines from four manufacturers (sanofi-pasteur, Novartis, CSL Limited, and MedImmune) to prevent 2009 H1N1 influenza. All of the currently approved influenza vaccine formulations, both seasonal and 2009 H1N1, are not adjuvanted. Two influenza vaccines (manufactured by GlaxoSmithKline and Novartis) with adjuvants are currently under study but not approved by FDA at this time.
Adjuvants have been added to vaccines since alum was first added to diphtheria toxoid in 1926.1 Adjuvants are chemicals that increase the immunogenicity of antigens that may not be immunogenic by itself or toxic in high doses to allow for smaller doses in the vaccine. Also, some adjuvants have been shown to prolong the duration of protection. Current vaccine adjuvants include mineral salts (aluminum and calcium), emulsions (such as M59 in Novartis’s influenza vaccine and ASO4 in GlaxoSmithKline’s influenza vaccine), particulate delivery vehicles (such as virus-like particles), microbial derivatives, and cells and cytokines.2 Vaccines that currently use adjuvants include DTaP, Tdap, some Hib vaccines, pneumococcal conjugate, hepatitis B, hepatitis A, HPV, anthrax, and rabies.
Because the purpose of the adjuvant is to increase the immunological response, then adverse effects are inherently possible. Large variables exist in how individual immune systems react to various adjuvants and the seriousness of the adverse effects. Many antivaccine groups have targeted adjuvants in their communications. Adjuvants historically have not been used in influenza vaccines. However, there is current interest in discovering an adjuvant so lower doses of antigen could be used, resulting in a larger quantity of vaccine being available. The World Health Organization is encouraging the use of adjuvants to increase supply for developing nations.3 However, it has been decided that adjuvanted vaccine would not be used in the United States because of concerns about potential adverse effects.
The current 2009 H1N1 vaccines were considered by FDA to be strain changes, not new vaccines, allowing for smaller studies to make the vaccine available sooner. Not to undermine the extent of the studies, but this is the same way that the seasonal vaccines are studied each year. Ongoing postmarketing surveillance will be an important aspect of the vaccine safety program. Only one of the two studies published recently on the 2009 H1N1 vaccine used Novartis’s adjuvanted influenza vaccine. The other used CSL Limited unadjuvanted vaccine.4,5 The trial of the Novartis vaccine investigated the vaccine with and without adjuvants and used various doses of antigen. Although the study had only 175 participants, the investigators were able to demonstrate that, at day 14 after vaccination, the adjuvanted vaccine at (7.5 mcg dose) had an adequate immunological response. They also reported mild adverse effects (most common were pain at injection site, usually without redness or swelling, and muscle aches), but no severe reactions were reported. Again, this vaccine is not available in the United States. This is only the first part of the study, with more to follow on the optimal dose.
Stephan L. Foster, PharmD
Professor and Vice Chair
College of Pharmacy
University of Tennessee
CAPT (Ret.) USPHS