tetano
Editor, Senior Moderator
Sci Adv
. 2021 Feb 5;7(6):eabe5819.
doi: 10.1126/sciadv.abe5819. Print 2021 Feb.
A lymph node-targeted Amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2
Martin P Steinbuck[SUP] 1 [/SUP], Lochana M Seenappa[SUP] 1 [/SUP], Aniela Jakubowski[SUP] 1 [/SUP], Lisa K McNeil[SUP] 1 [/SUP], Christopher M Haqq[SUP] 2 [/SUP], Peter C DeMuth[SUP] 1 [/SUP]
Affiliations
Abstract
The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (T[SUB]H[/SUB]1) cytokines and trafficked into lung parenchyma. Antibody responses favored T[SUB]H[/SUB]1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.
. 2021 Feb 5;7(6):eabe5819.
doi: 10.1126/sciadv.abe5819. Print 2021 Feb.
A lymph node-targeted Amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2
Martin P Steinbuck[SUP] 1 [/SUP], Lochana M Seenappa[SUP] 1 [/SUP], Aniela Jakubowski[SUP] 1 [/SUP], Lisa K McNeil[SUP] 1 [/SUP], Christopher M Haqq[SUP] 2 [/SUP], Peter C DeMuth[SUP] 1 [/SUP]
Affiliations
- PMID: 33547083
- DOI: 10.1126/sciadv.abe5819
Abstract
The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (T[SUB]H[/SUB]1) cytokines and trafficked into lung parenchyma. Antibody responses favored T[SUB]H[/SUB]1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.