Salmonella flagellins are potent adjuvants for intranasally administered whole inactivated influenza vaccine

Abstract

Bacterial flagellins are potent inducers of innate immune responses in the mouse lung because they bind to TLR5 expressed on the apical surfaces of airway epithelial cells. TLR engagement leads to the initiation of a signaling cascade that results in a pro-inflammatory response with subsequent up-regulation of several cytokines and leads to adaptive immune responses. We examined the ability of two soluble flagellins, a monomeric flagellin expressed in E. coli and a highly purified polymeric flagellin directly isolated from Salmonella, to enhance the efficacy of influenza vaccines in mice. Here we demonstrate that both flagellins co-administered intranasally with inactivated A/PR/8/34 (PR8) virus induced robust increases of systemic influenza-specific IgA and IgG titers and resulted in a more comprehensive humoral response as indicated by the increase of IgG2a and IgG2b subclass responses. Groups immunized with the adjuvanted vaccines were fully protected against high dose lethal challenge by homologous virus whereas inactivated PR8 alone conferred only partial protection. Finally we show that shortly after immunization the adjuvanted vaccines induced a dramatic increase in pro-inflammatory cytokines in the lung, resulting in extensive lung infiltration by granulocytes and monocytes/macrophages. Our results reveal a promising perspective for the use of both soluble monomeric and polymeric flagellin as mucosal vaccine adjuvants to improve protection against influenza epidemics as well as a range of other infectious diseases.

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

“…Flagellin (flg) is a TLR5 agonist that has proven to be a potent adjuvant for the induction of antibody responses in a number of experimental animal models (for reviews, see references 36 and 37). Studies in mice showed that its inclusion in an inactivated influenza virus vaccine resulted in enhanced virus-specific antibody and increased protection (38).…”

Candidate vaccine construction against tick-born encephalitis based on hybrid recombinant flagG-protE-protein

“…До применения флагеллина пожилые люди слабо реагировали на вакцинацию и заболевали гриппом. Таким образом, продемонстрировано, что флагеллин обладает потенциалом для стимулирования врожденного и приоб-ретенного иммунитета, причем формирует гуморальный и клеточный иммунный ответы при вакцинации (Mizel, Bates, 2010;Skountzou et al, 2010;Girard et al, 2011).…”

Chimeric flagellin expressed by Salmonella typhimurium induces an ESAT-6-specific Th1-type immune response and CTL effects following intranasal immunization

“…Flagellin is a highly conserved bacterial protein that elicits TLR-5-dependent inflammatory responses in both animal and plants. 19 Previous studies have investigated the ability of flagellin to elicit antigen-specific T-cell responses when delivered as live attenuated vaccines. 20,21 In addition, Salmonella flagellin has previously been used as an adjuvant and carrier for a synthetic peptide and to potentiate antibody production against a cholera toxin epitope.…”