Toll‐like receptor 4 signalling regulates antibody response to adenoviral vector‐based vaccines by imprinting germinal centre quality

摘要

Summary Adenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of Toll‐like receptors ( TLR s) participate in the adenovirus‐induced adaptive immune response, yet there is little information regarding the role of TLR 4 in AdV‐induced immune responses in recent literature. We investigated the function of TLR 4 in both adaptive and innate immune responses to an AdV‐based anthrax vaccine. By immunizing wild‐type and TLR 4 knockout ( TLR 4‐ KO ) mice, we revealed the requirement of TLR 4 in AdV‐induced innate responses. We also showed that TLR 4 functions are required for germinal centre responses in immunized mice, as expression of the apoptosis‐related marker Fas was down‐regulated on germinal centre B cells from TLR 4‐ KO mice. Likewise, decreased expression of inducible costimulator on follicular T helper cells was observed in immunized TLR 4‐ KO mice. Moreover, a potent protective antigen‐specific humoral immune response was mimicked using an adjuvant system containing the TLR 4 agonist monophosphoryl lipid A. Overall, our findings showed that very rapid antigen‐specific antibody production is correlated with the TLR 4‐imprinted germinal centre response to AdV‐based vaccine. These results provide additional evidence for the use of the AdV and a TLR agonist to induce humoral responses. Our findings offer new insights into rational vaccine design.