Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants

Authors:

• Montgomerie, Isabelle
• Bird, Thomas W.
• Palmer, Olga R.
• Mason, Ngarangi C.
• Pankhurst, Theresa E.
• Lawley, Blair
• Hernández, Leonor C.
• Harfoot, Rhodri
• Authier-Hall, Astrid
• Anderson, Danielle E.
• Hilligan, Kerry L.
• Buick, Kaitlin H.
• Mbenza, Naasson M.
• Mittelstädt, Gerd
• Maxwell, Samara
• Sinha, Shubhra
• Kuang, Joanna
• Subbarao, Kanta
• Parker, Emily J.
• Sher, Alan
• Hermans, Ian F.
• Ussher, James E.
• Quiñones-Mateu, Miguel E.
• Comoletti, Davide
• Connor, Lisa M.

Details:

iScience, Volume 26, Issue 4, 2023-04-21

Article Link: Click here

Emerging SARS-CoV-2 variants pose a threat to human health worldwide. SARS-CoV-2 receptor binding domain (RBD)-based vaccines are suitable candidates for booster vaccines, eliciting a focused antibody response enriched for virus neutralizing activity. Although RBD proteins are manufactured easily, and have excellent stability and safety properties, they are poorly immunogenic compared to the full-length spike protein. We have overcome this limitation by engineering a subunit vaccine composed of an RBD tandem dimer fused to the N-terminal domain (NTD) of the spike protein. We found that inclusion of the NTD (1) improved the magnitude and breadth of the T cell and anti-RBD response, and (2) enhanced T follicular helper cell and memory B cell generation, antibody potency, and cross-reactive neutralization activity against multiple SARS-CoV-2 variants, including B.1.1.529 (Omicron BA.1). In summary, our uniquely engineered RBD-NTD-subunit protein vaccine provides a promising booster vaccination strategy capable of protecting against known SARS-CoV-2 variants of concern.