Two small molecules activate an innate immune enzyme to improve RSV vaccines.

Vaccines often need helper ingredients, called adjuvants, to boost the body's immune response. Our cells naturally make a protective molecule called 2-5A2-5AA short chain of nucleotides that acts as a signal to activate a cell's virus-fighting machinery. to fight viruses and alert immune cells. However, natural 2-5A breaks down too fast to work inside vaccines. To solve this problem, researchers designed stable chemical compounds called benzothiazole derivatives. These molecules target and turn on an enzyme called OAS, which causes the body to produce its own 2-5A. The team identified two top molecules, named CG and DG. When tested with a model antigen, both compounds matured dendritic cells and raised IgG antibody levels. Furthermore, pairing CG or DG with an RSV virus antigen boosted neutralizing antibodies as well as memory B and T cells. This shows they can serve as reliable vaccine adjuvants.

Why it matters

Respiratory syncytial virus (RSV) causes severe illness in infants and older adults, but vaccines have struggled to produce strong, lasting immunity. These two benzothiazole compounds, CG and DG, act as adjuvants by activating a natural antiviral pathway (OAS-2-5A-RIG-I), leading to more memory B and T cells and higher neutralizing antibodies. Because they are small stable molecules with a clear target, they could be easier to manufacture and combine with existing vaccines than current adjuvants.

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