Incorporation of SARS-CoV-2 spike NTD to RBD protein vaccine improves immunity against viral variants
Isabelle Montgomerie, Thomas W. Bird, Olga R. Palmer, Ngarangi C. Mason, Theresa E. Pankhurst, Blair Lawley, Leonor C. Hernández, Rhodri Harfoot, Astrid Authier-Hall, Danielle E. Anderson, Kerry L. Hilligan, Kaitlin H. Buick, Naasson M. Mbenza, Gerd Mittelstädt, Samara Maxwell, Shubhra Sinha, Joanna Kuang, Kanta Subbarao, Emily Jane Parker, Alan Sher, Ian F. Hermans, James E. Ussher, Miguel E. Quiñones‐Mateu, Davide Comoletti, Lisa M. Connor
Abstract
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.