tetano
Editor, Senior Moderator
Mol Ther Methods Clin Dev
. 2024 Nov 15;32(4):101380.
doi: 10.1016/j.omtm.2024.101380. eCollection 2024 Dec 12. mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting
Hareth A Al-Wassiti[SUP] 1 [/SUP], Stewart A Fabb[SUP] 1 [/SUP], Samantha L Grimley[SUP] 2 [/SUP], Ruby Kochappan[SUP] 1 [/SUP], Joan K Ho[SUP] 1 [/SUP], Chinn Yi Wong[SUP] 2 [/SUP], Chee Wah Tan[SUP] 3 [/SUP], Thomas J Payne[SUP] 1 [/SUP], Asuka Takanashi[SUP] 1 [/SUP], Chee Leng Lee[SUP] 1 [/SUP], Rekha Shandre Mugan[SUP] 1 [/SUP], Horatio Sicilia[SUP] 1 [/SUP], Serena L Y Teo[SUP] 1 [/SUP], Julie McAuley[SUP] 2 [/SUP], Paula Ellenberg[SUP] 2 [/SUP], James P Cooney[SUP] 4 5 [/SUP], Kathryn C Davidson[SUP] 4 [/SUP], Richard Bowen[SUP] 6 [/SUP], Marc Pellegrini[SUP] 4 [/SUP], Steven Rockman[SUP] 2 7 [/SUP], Dale I Godfrey[SUP] 2 [/SUP], Terry M Nolan[SUP] 2 [/SUP], Lin-Fa Wang[SUP] 3 [/SUP], Georgia Deliyannis[SUP] 2 [/SUP], Damian F J Purcell[SUP] 2 [/SUP], Colin W Pouton[SUP] 1 [/SUP]
Affiliations
We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole-spike vaccines, sVNT studies suggested that BA.1 and BA.5 RBD-TM vaccines had the potential to overcome the detrimental effects of immune imprinting. A subsequent heterologous boost study using XBB.1.5 booster vaccines was evaluated using both sVNT and authentic virus neutralization. Geometric mean XBB.1.5 neutralization values after third-dose RBD-TM or whole-spike XBB.1.5 booster vaccines were compared with those after a third dose of ancestral spike booster vaccine. Fold-improvement over ancestral vaccine was just 1.3 for the whole-spike XBB.1.5 vaccine, similar to data published using human serum samples. In contrast, the fold-improvement achieved by the RBD-TM XBB.1.5 vaccine was 16.3, indicating that the RBD-TM vaccine induced the production of antibodies that neutralize the XBB.1.5 variant despite previous exposure to ancestral spike protein.
Keywords: COVID vaccine; anchored RBD vaccine; immune imprinting; lipid nanoparticle; mRNA vaccine; virus neutralization.
. 2024 Nov 15;32(4):101380.
doi: 10.1016/j.omtm.2024.101380. eCollection 2024 Dec 12. mRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting
Hareth A Al-Wassiti[SUP] 1 [/SUP], Stewart A Fabb[SUP] 1 [/SUP], Samantha L Grimley[SUP] 2 [/SUP], Ruby Kochappan[SUP] 1 [/SUP], Joan K Ho[SUP] 1 [/SUP], Chinn Yi Wong[SUP] 2 [/SUP], Chee Wah Tan[SUP] 3 [/SUP], Thomas J Payne[SUP] 1 [/SUP], Asuka Takanashi[SUP] 1 [/SUP], Chee Leng Lee[SUP] 1 [/SUP], Rekha Shandre Mugan[SUP] 1 [/SUP], Horatio Sicilia[SUP] 1 [/SUP], Serena L Y Teo[SUP] 1 [/SUP], Julie McAuley[SUP] 2 [/SUP], Paula Ellenberg[SUP] 2 [/SUP], James P Cooney[SUP] 4 5 [/SUP], Kathryn C Davidson[SUP] 4 [/SUP], Richard Bowen[SUP] 6 [/SUP], Marc Pellegrini[SUP] 4 [/SUP], Steven Rockman[SUP] 2 7 [/SUP], Dale I Godfrey[SUP] 2 [/SUP], Terry M Nolan[SUP] 2 [/SUP], Lin-Fa Wang[SUP] 3 [/SUP], Georgia Deliyannis[SUP] 2 [/SUP], Damian F J Purcell[SUP] 2 [/SUP], Colin W Pouton[SUP] 1 [/SUP]
Affiliations
- PMID: 39687732
- PMCID: PMC11646785
- DOI: 10.1016/j.omtm.2024.101380
We investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole-spike vaccines, sVNT studies suggested that BA.1 and BA.5 RBD-TM vaccines had the potential to overcome the detrimental effects of immune imprinting. A subsequent heterologous boost study using XBB.1.5 booster vaccines was evaluated using both sVNT and authentic virus neutralization. Geometric mean XBB.1.5 neutralization values after third-dose RBD-TM or whole-spike XBB.1.5 booster vaccines were compared with those after a third dose of ancestral spike booster vaccine. Fold-improvement over ancestral vaccine was just 1.3 for the whole-spike XBB.1.5 vaccine, similar to data published using human serum samples. In contrast, the fold-improvement achieved by the RBD-TM XBB.1.5 vaccine was 16.3, indicating that the RBD-TM vaccine induced the production of antibodies that neutralize the XBB.1.5 variant despite previous exposure to ancestral spike protein.
Keywords: COVID vaccine; anchored RBD vaccine; immune imprinting; lipid nanoparticle; mRNA vaccine; virus neutralization.