| Title: |
The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice |
| Authors: |
Do, Kim Thi Hoang; Willenzon, Stefanie; Ristenpart, Jasmin; Janssen, Anika; Volz, Asisa; Sutter, Gerd; Förster, Reinhold; Bošnjak, Berislav |
| Publisher Information: |
Frontiers Media SA |
| Publication Year: |
2023 |
| Subject Terms: |
article; ddc:610; CD8-Positive T-Lymphocytes; Animals; Mice; Inbred C57BL; Vaccinia virus; Vaccines; Adjuvants; Immunologic; Antibodies; Viral; Administration; Intranasal; Toll-Like Receptor 3; Toll-Like Receptor 4; Toll-Like Receptor 9; COVID-19; SARS-CoV-2; Vaccination; Respiratory Tract; Modified Vaccinia Virus Ankara (Mva); Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-cov-2); Toll-like Receptor (Tlr) Agonist |
| Description: |
Background and aims Modified Vaccinia virus Ankara (MVA) represents a promising vaccine vector for respiratory administration to induce protective lung immunity including tertiary lymphoid structure, the bronchus-associated lymphoid tissue (BALT). However, MVA expressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein (MVA-SARS-2-S) required prime-boost administration to induce high titers of anti-Spike antibodies in serum and bronchoalveolar lavage (BAL). As the addition of adjuvants enables efficient tailoring of the immune responses even to live vaccines, we tested whether Toll-like receptor (TLR)-agonists affect immune responses induced by a single dose of intranasally applied MVA-SARS-2-S. Methods We intranasally immunized C57BL/6 mice with MVA-SARS-2-S vaccine in the presence of either TLR3 agonist polyinosinic polycytidylic acid [poly(I:C)], TLR4 agonist bacterial lipopolysaccharide (LPS) from Escherichia coli, or TLR9 agonist CpG oligodeoxynucleotide (CpG ODN) 1826. At different time-points after immunization, we analyzed induced immune responses using flow cytometry, immunofluorescent microscopy, and ELISA. Results TLR agonists had profound effects on MVA-SARS-2-S-induced immune responses. At day 1 post intranasal application, the TLR4 agonist significantly affected MVA-induced activation of dendritic cells (DCs) within the draining bronchial lymph nodes, increasing the ratio of CD11b+CD86+ to CD103+CD86+ DCs. Nevertheless, the number of Spike-specific CD8+ T cells within the lungs at day 12 after vaccination was increased in mice that received MVA-SARS-2-S co-administered with TLR3 but not TLR4 agonists. TLR9 agonist did neither significantly affect MVA-induced DC activation nor the induction of Spike-specific CD8+ T cells but reduced both number and size of bronchus-associated lymphoid tissue. Surprisingly, the addition of all TLR agonists failed to boost the levels of Spike-specific antibodies in serum and bronchoalveolar lavage. Conclusions Our study indicates a ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Frontiers in Cellular and Infection Microbiology -- Front Cell Infect Microbiol -- http://www.frontiersin.org/cellular_and_infection_microbiology/archive -- https://www.ncbi.nlm.nih.gov/pmc/journals/1860/ -- http://www.bibliothek.uni-regensburg.de/ezeit/?2619676 -- 2235-2988; https://doi.org/10.3389/fcimb.2023.1259822 |
| DOI: |
10.3389/fcimb.2023.1259822 |
| Availability: |
https://doi.org/10.3389/fcimb.2023.1259822; https://mhh-publikationsserver.gbv.de/receive/mhh_mods_00002599; https://mhh-publikationsserver.gbv.de/servlets/MCRFileNodeServlet/mhh_derivate_00002480/fcimb-13-1259822_a.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ ; public ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.E4CBDCFF |
| Database: |
BASE |