Vaccines exert a tremendous effect on the prevention of infectious diseases. Infectious disease vaccines contain components of microorganisms, which make the vaccine consisting of an antigen (Ag) and an immunostimulatory substance (a pattern molecule, a ligand of Toll-like receptor (TLR), etc.). It is due to pattern molecules that side effects (fever, fatigue, nausea, etc.) occur after vaccination. Synthesis or highly purified antigens lose pattern molecules, which increases safety but reduces vaccine activity as seen in the current influenza vaccine.
Pattern molecules exogenously added to purified antigens are called adjuvants. Such a vaccine can be designed to be noninfectious and is called a subcomponent vaccine. The advantage is that both antigens and pattern molecules can be structurally defined, and safety can be individually tested in advance.
Adjuvants are indispensable for activating innate immunity to induce cellular immunity but have been made indivisible from inflammation. Existing adjuvants such as Alum cause inflammatory reactions but do not directly activate TLR. Therefore, induction of cellular immunity is too weak to adapt for anticancer immunity.
Human antigen-presenting dendritic cells were found to express only TLR2 and TLR3. TLR2 recognizes bacterial lipoprotein and peptidoglycan. BCG-CWS is an agonist of TLR2. TLR3 recognizes poly I: C. It was known that antiviral antitumor activity is strong against viral double-stranded (ds) RNA (polyI: C is its analog). Many clinical trials using polyI: C were performed, but tumor regression was seen with effective dose, where serious adverse events developed and described as 'untolerable'. If these are modified to develop non-inflammatory adjuvants, it will be possible to create highly safe memory vaccines. Adjuvants can also be applied to prophylactic vaccines against infectious diseases, and development of non-inflammatory adjuvants beyond Alum is expected.