Currently, there are a limited number of approved adjuvants available for vaccine formulation. These include alum, MF59 (oil/water emulsion), AS03 (oil/water emulsion), a virosome, and AS04 (alum-adsorbed TLR4 agonist). Alum has been in use since 1926, while AS04 is the newest approved adjuvant and has been in use since 2005 [1]. While these have sufficed thus far for the vaccinations normally administered throughout life, a 2015 article from Immune Network points out that, “new vaccine targets require the induction of well-defined CMI [cell-mediated immunity] in addition to high titer of antibody. Consequently, new immunostimulant adjuvants in vaccine formulations are needed in order to stimulate robust immune responses including humoral immunity and CMI” [1].

The article details several classes of adjuvants that are undergoing clinical trials. TLR (toll-like receptor) agonists are one of the subsets being tested. As Lee and Nguyen state, “TLRs provide a bridge between innate and adaptive immunity,” so TLR agonists as adjuvants have the potential to provide a full immune response as well as a response that is more selectively targeted than one elicited by, for example, alum [1]. There are three TLR agonist adjuvants mentioned in the paper as undergoing clinical trials: CpG, which, unsurprisingly, is composed of CpG oligonucleotides and is a TLR 9 agonist; flagellin (linked to the antigen), a TLR 5 agonist; and PolyI:C, composed of dsRNA analogues and is a TLR 3 agonist [1]. Thus far in their testing, these adjuvants have been shown to enhance antibody titer as well as successfully stimulate the TLR signaling pathway, causing release of several proinflammatory cytokines and subsequent stimulation of CMI [1].

Some researchers are investigating the use of cytokines themselves as adjuvants. A paper published just a few days ago in BMC Immunology reports cautiously promising results with use of a cytokine adjuvant in an immunotherapy treatment for colon cancer. They used the cytokines GM-CSF and IL-2 in their vaccine. Among other things, they measured tumor growth and survival in mice injected with CT26.WT (colon cancer cells), and found that tumor growth was “significantly inhibited” and the survival period for vaccinated mice was at least 160 days longer than that of unvaccinated mice [2].

Below is a nice picture from their experiment—if you look at panel B, you can see all the tumors resected from the mice in that particular portion of the experiment. The sample size in each group was quite small, so hopefully these results are replicable on a larger scale! 

[1] Lee, Sujin, and Minh Trang Nguyen. 2015. “Recent Advances of Vaccine Adjuvants for Infectious Diseases.” Immune Network 15.2: 51–57.

[2] Ju, H. et al. 2016. “An effective cytokine adjuvant vaccine induces autologous T-cells response against colon cancer in an animal model.” BMC Immunology 17:31.