tetano
Editor, Senior Moderator
Front Cell Infect Microbiol
. 2023 Oct 3:13:1259822.
doi: 10.3389/fcimb.2023.1259822. eCollection 2023. The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice
Kim Thi Hoang Do[SUP] 1 [/SUP], Stefanie Willenzon[SUP] 1 [/SUP], Jasmin Ristenpart[SUP] 1 [/SUP], Anika Janssen[SUP] 1 [/SUP], Asisa Volz[SUP] 2 3 [/SUP], Gerd Sutter[SUP] 3 4 [/SUP], Reinhold Förster[SUP] 1 5 6 [/SUP], Berislav Bošnjak[SUP] 1 5 [/SUP]
Affiliations
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[SUP]+[/SUP]CD86[SUP]+[/SUP] to CD103[SUP]+[/SUP]CD86[SUP]+[/SUP] DCs. Nevertheless, the number of Spike-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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 potential role of TLR-agonists as a tool to modulate immune responses to live vector vaccines. Particularly TLR3 agonists hold a promise to potentiate MVA-induced cellular immune responses. On the other hand, additional research is necessary to identify optimal combinations of agonists that could enhance MVA-induced humoral responses.
Keywords: Toll-like receptor (TLR) agonist; modified vaccinia virus Ankara (MVA); respiratory tract; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination.
. 2023 Oct 3:13:1259822.
doi: 10.3389/fcimb.2023.1259822. eCollection 2023. The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice
Kim Thi Hoang Do[SUP] 1 [/SUP], Stefanie Willenzon[SUP] 1 [/SUP], Jasmin Ristenpart[SUP] 1 [/SUP], Anika Janssen[SUP] 1 [/SUP], Asisa Volz[SUP] 2 3 [/SUP], Gerd Sutter[SUP] 3 4 [/SUP], Reinhold Förster[SUP] 1 5 6 [/SUP], Berislav Bošnjak[SUP] 1 5 [/SUP]
Affiliations
- PMID: 37854858
- PMCID: PMC10580083
- DOI: 10.3389/fcimb.2023.1259822
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[SUP]+[/SUP]CD86[SUP]+[/SUP] to CD103[SUP]+[/SUP]CD86[SUP]+[/SUP] DCs. Nevertheless, the number of Spike-specific CD8[SUP]+[/SUP] 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[SUP]+[/SUP] 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 potential role of TLR-agonists as a tool to modulate immune responses to live vector vaccines. Particularly TLR3 agonists hold a promise to potentiate MVA-induced cellular immune responses. On the other hand, additional research is necessary to identify optimal combinations of agonists that could enhance MVA-induced humoral responses.
Keywords: Toll-like receptor (TLR) agonist; modified vaccinia virus Ankara (MVA); respiratory tract; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination.