Lipid A mimetic BECC438 potentiates durable and balanced antibody responses in an ovalbumin murine model of vaccination.

Abstract

The need for effective infectious disease vaccines has become an inescapable topic in recent years. Continued development of next-generation vaccines that provide robust protective immunity is imperative. Such vaccines will likely include adjuvants that avoid excessive adverse reactions while allowing for dose and antigen sparing. Bacterially derived TLR4 agonist, BECC438, has recently emerged as a lead adjuvant candidate across several experimental models of infectious disease, including Yersinia pestis (plague), human papillomavirus, influenza A (flu), SARS-CoV-2 (COVID-19), and Shigella spp (gastrointestinal infection). To confirm that BECC438 is a high-quality immunoadjuvant, even without antigen from an infectious pathogen, studies presented here use the model antigen ovalbumin in a murine prime-boost vaccine model. Durable and more balanced production of antibody isotypes IgG1 and IgG2 is observed when the bacterial enzyme combinatorial chemistry adjuvant is used, as compared with the classic adjuvants aluminum salts (Alhydrogel) and synthetic monophosphorylated lipid A-PHAD (phosphorylated hexaacyl disaccharide). Antibody responses are maintained for at least 18 wk postvaccination. Observed immune metrics maintained similar trends across males, females, and genetic backgrounds, including C57BL/6, BALB/c, and CD-1 (outbred) mice, with males overall showing a lower production of IgG2c. In vitro analysis of C57BL/6 serum showed an increased half-life of ovalbumin-specific antibodies in BECC438 adjuvanted animals, indicative of a higher antigen binding affinity. These studies provide continued evidence to support the development of the BECC438 adjuvant in vaccines for human use.