Enhancing the protection of influenza virus vaccines with BECC TLR4 adjuvant in aged mice

Abstract

Influenza A virus (IAV) is a leading cause of respiratory disease worldwide often resulting in severe morbidity and mortality. We have previously shown that the Bacterial Enzymatic Combinatorial Chemistry (BECC) adjuvants, BECC438 and BECC470, formulated with an influenza virus hemagglutinin (HA) protein vaccine, offer greater protection from influenza virus challenge in mouse respiratory models using adult mice than standard HA:adjuvant combinations. In this study, we determined that immunization with HA + BECC adjuvants also significantly broadened the epitopes targeted on HA as compared with other adjuvants, resulting in increased titers of antibodies directed against the highly conserved HA stalk domain. Importantly, we demonstrate that BECC470 combined with an influenza virus HA protein antigen in a prime-only immunization regimen was able to achieve complete protection from challenge in a ~ 12-month-old mouse aged model. Together, this demonstrates the heightened protection provided by the BECC470 adjuvant in an influenza virus vaccine model and shows the enhanced immune response, as compared to other adjuvants elicited by the formulation of HA with BECC470.

BECC-engineered live-attenuated Shigella vaccine candidates display reduced endotoxicity with robust immunogenicity in mice

“…The lipid A modifications engineered in this study utilized the BECC approach whereby prior identification of lipid A modifying enzymes from a variety of Gram-negative bacteria then enabled the expression of select enzymes within a bacterium of interest. Previously, the BECC system has been employed to generate custom-designed lipid A molecules in Yersinia [50][51][52][53][54][55][56] ; however, this study extends its use to Shigella species, suggesting it is applicable to a variety of Gram-negative bacteria. More specifically, we showed that BECC enabled robust lipid A modification in both WT and vaccine strains of Shigella.…”

BECC438b TLR4 agonist supports unique immune response profiles from nasal and muscular DTaP pertussis vaccines in murine challenge models

“…Future studies to more clearly define the immunostimulatory effects of BECC438b during vaccination against respiratory pathogens are warranted to better understand the data observed in this study. BECC technology used as adjuvants in vaccines against respiratory diseases like influenza has been explored previously with great success ( 95 , 96 ). While these applications did not explore route of administration, we believe our data prepare a case for its efficacy in novel intranasal vaccines.…”

Dietary supplementation with spray-dried animal plasma improves vaccine protection in aged mice

“…Moreover, commensal bacteria are known to play a role in shaping the immune system tone, which may also influence vaccine efficacy (51). Recently, a study observed that potentiation of the innate immune response through Toll Like Receptor (TLR)-4 could enhance vaccine protection against influenza viruses in senescent mice (52). Given that SDP In conclusion, in this study, we have established a model of nasal immunization in senescent mice that protected them mucosally and systemically, as reflected by increased levels of anti-SEB-specific Igs and a higher survival rate to lethal shock with SEB.…”