Novel TLR4 adjuvant elicits protection against homologous and heterologous Influenza A infection. Issue 36 (23rd August 2021)

• Record Type: Journal Article
• Authors: Haupt, Robert E.; Harberts, Erin M.; Kitz, Robert J.; Strohmeier, Shirin; Krammer, Florian; Ernst, Robert K.; Frieman, Matthew B.
• Is Part Of: Vaccine. Volume 39:Issue 36(2021)
• Page Start: 5205
• Page End: 5213
• Publication Date: 2021-08-23
• Subjects: Vaccine -- Influenza -- Adjuvant -- TLR4 agonist -- Cross-protection; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.06.085
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Seasonal influenza A causes significant morbidity and mortality worldwide. Annually influenza vaccines are on average only 40–60% effective. Adjuvanted vaccines enhance and shape immune responses to vaccines. Novel BECC TLR4 ligands adjuvant flu vaccines to induce a balanced Th1/Th2 response. BECC adjuvants protect from homologous and heterologous flu infection in mice. Abstract: Influenza A virus (IAV) is a leading cause of respiratory disease worldwide often resulting in hospitalization or death. In this study, TLR4 immunostimulatory molecules, Bacterial Enzymatic Combinatorial Chemistry (BECC) 438 and BECC470 were found to be superior IAV vaccine adjuvants when compared to the classic adjuvant alhydrogel (alum) and Phosphorylated Hexa-Acyl Disaccharide (PHAD), a synthetic TLR4 agonist. BECC molecules allow for antigen sparing of a recombinant HA (rHA) protein, elicit a more balanced IgG1/IgG2a response, and were protective in a prime only dosing schedule. Importantly, BECC molecules afford protection from a heterologous IAV strain demonstrating that a cross-protective influenza vaccine is possible when the antigen is effectively adjuvanted.