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

• DOI: 10.1111/imm.12957
• Publication Date: 2018-06-07T07:52:41Z
• Authors: Ruihua Li; Ju Liu; Shipo Wu; Xiaodong Zai; Yaohui Li; Qiaoling Yang; Lihua Hou; Junjie Xu; Wei Chen
• Keywords: Mice, Knockout; B-Lymphocytes; Vaccines; Genetic Vectors; Germinal Center; Models, Biological; Antibodies; Adenoviridae; Cell Line; 3. Good health; Toll-Like Receptor 4; Mice; 03 medical and health sciences; 0302 clinical medicine; T-Lymphocyte Subsets; Antibody Formation; Animals; Cytokines; Humans; Female; Signal Transduction

SummaryAdenoviral vectors (AdV) are considered promising candidates for vaccine applications. A prominent group of Toll‐like receptors (TLRs) participate in the adenovirus‐induced adaptive immune response, yet there is little information regarding the role of TLR4 in AdV‐induced immune responses in recent literature. We investigated the function of TLR4 in both adaptive and innate immune responses to an AdV‐based anthrax vaccine. By immunizing wild‐type and TLR4 knockout (TLR4‐KO) mice, we revealed the requirement of TLR4 in AdV‐induced innate responses. We also showed that TLR4 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 TLR4‐KO mice. Likewise, decreased expression of inducible costimulator on follicular T helper cells was observed in immunized TLR4‐KO mice. Moreover, a potent protective antigen‐specific humoral immune response was mimicked using an adjuvant system containing the TLR4 agonist monophosphoryl lipid A. Overall, our findings showed that very rapid antigen‐specific antibody production is correlated with the TLR4‐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.