TY - JOUR
T1 - Enhancing the protection of influenza virus vaccines with BECC TLR4 adjuvant in aged mice
AU - Haupt, Robert
AU - Baracco, Lauren
AU - Harberts, Erin M.
AU - Loganathan, Madhumathi
AU - Kerstetter, Lucas J.
AU - Krammer, Florian
AU - Coughlan, Lynda
AU - Ernst, Robert K.
AU - Frieman, Matthew B.
N1 - Funding Information:
This work was supported in part by funding as follows: REH is supported by the U.S. Army’s Long Term Health and Education Training Program, MBF is partially supported by BARDA# ASPR-20–01495 and NIH #75N93019C00051. LC is supported by R21AI146529. Funding for work in the Krammer laboratory was provided by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 and the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014.
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85146300039&partnerID=8YFLogxK
U2 - 10.1038/s41598-023-27965-x
DO - 10.1038/s41598-023-27965-x
M3 - Article
C2 - 36639569
AN - SCOPUS:85146300039
SN - 2045-2322
VL - 13
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 715
ER -