Vaccine Adjuvants: Is a Little Pain Worth the Gain?

December 10, 2015

Research on safety and side effects associated with the compounds used in vaccines to boost immune response says the answer is, "Yes."

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A new flu vaccine, Fluad® (Novartis), was approved by the FDA in November, adding to the crowded field of available vaccine choices:  live versus inactive forms, quadravalent or trivalent, preservative-free or not, given IM or intradermal, high dose or regular dose, made with eggs or totally egg-free. What makes Fluad different is that it is the first “adjuvanted” flu vaccine available in the United States and uses a different adjuvant than has previously been approved for use in the US. Adjuvants are compounds added to vaccines to boost the immune response and have been used for decades. Fluad is specifically indicated, and was "designed" for adults older than age 65. Researchers continue to look for ways to better protect this population against influenza since this group has the highest death rate from the flu and in general these adults have the lowest antibody response to a standard flu vaccine-the result of a less robust immune system.

Now, let's see what you know about adjuvants.

Which of the following statements is NOT true?

A. No live vaccines contain adjuvants. 

B.  All the DTaP and Tdap vaccines contain adjuvants. 

C. Some HIB vaccines contain adjuvants and some don't.

D. Anti-vaxxers aren't worried about adjuvants, at least not yet.

For answer and discussion, please click here.

Answer: Read on…

Live vaccines do a very good job of stimulating the innate immune system and none have or need adjuvants. Not only do all the DTaP and Tdap vaccines contain adjuvants, so do all the available DT and dT vaccines. The Merck Hib vaccine, PedvaxHIB, is the only Hib vaccine containing an adjuvant, and does such a good job of boosting the immune response that a 3rd dose at 6 months is not needed.  It is also the only Hib vaccine that induces significant antibody levels after a single dose in the under-6-months-of-age child.

Sanofi's ActHIB and Glaxo's Hiberix do not contain an adjuvant. ActHIB does need a third dose given at 6 months of age. Hiberix is only recommended for children over one-year of age. Some anti-vaxxers rail against adjuvants voicing concerns about the added aluminum and the “toxin” present in Cervarix and even that the adjuvants “turbocharge” the vaccine, which apparently they perceive as a negative. Until Fluad's approval, only two adjuvants had been approved for use in the US:  aluminum salts and monophosphoryl lipid A (a component of bacterial cell walls), the latter used only by Glaxo in Cervarix. Like many of the arguments of the anti-vaccine crowd, a bit of truth gets distorted. Aluminum in large doses can cause neurologic problems. But let's look at the reality: Infants getting numerous adjuvanted vaccines in their first 6 months of life receive a total dose of aluminum of less than 5 mg. Breast fed babies get about 7 mg from breast milk and formula fed babies between 38 and 117 mg depending upon the formula used during their first 6 months. Adults eat between 7and 9 mg of aluminum on average every day. I tell parents the “poison is in the dose” for most chemical compounds. I then tell them that the chemical coming out of their kitchen tap is something that in a large enough dose can cause hyponatremia and seizures and possibly even permanent brain damage. That chemical is, of course, H2O.

To be honest, it is not totally understood how adjuvants boost the immune response. Theories include that they work by inducing inflammation at the site and/or by retaining antigen at the site and promoting uptake by the dendritic cells important to the immune response. Data also exist to suggest that adjuvants may cause “epitope spread.” Epitopes are the specific part of an antigen that the body recognizes and can make antibodies against. The more epitopes on a given antigen, the better the antibody response.

Adjuvants have been extensively studied for safety. A meta-analysis published in the Lancet in 2004 looked at reactions to adjuvanted and non-adjuvanted DTaP vaccines. The children under the age of 18 months who received the adjuvanted vaccine did have about twice the erythema and induration at the injection site as compared to children receiving an aluminum hydroxide-free form of the vaccine, but no difference in significant systemic effects was seen. Children over 18 months of age receiving the adjuvanted vaccine had more pain at the injection site, but no increase in erythema, induration, or fever.

So, to answer the question asked originally asked, I will quote Gary Marshall, MD, “In a sense, the pain is part of the gain-the irritation or inflammation (and hence pain) caused by the adjuvant also drives the immune response.” 

Your high school football coach would be proud of you for using adjuvanted vaccines.