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 J Parker; Alan Sher; Ian F Hermans; James E Ussher; Miguel E Quiñones-Mateu; Davide Comoletti; Lisa M Connor; VAANZ Group

doi:10.1016/j.isci.2023.106256

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

iScience. 2023 Apr 21;26(4):106256. doi: 10.1016/j.isci.2023.106256. Epub 2023 Feb 20.

Authors

Isabelle Montgomerie¹, Thomas W Bird¹, Olga R Palmer², Ngarangi C Mason², Theresa E Pankhurst², Blair Lawley³, Leonor C Hernández³, Rhodri Harfoot³, Astrid Authier-Hall², Danielle E Anderson⁴, Kerry L Hilligan^{2

5}, Kaitlin H Buick², Naasson M Mbenza¹, Gerd Mittelstädt⁶, Samara Maxwell¹, Shubhra Sinha³, Joanna Kuang³, Kanta Subbarao^{4

7}, Emily J Parker⁶, Alan Sher⁵, Ian F Hermans², James E Ussher³, Miguel E Quiñones-Mateu^{3

8}, Davide Comoletti¹, Lisa M Connor^{1

2}; VAANZ Group

Affiliations

¹ School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
² Malaghan Institute of Medical Research, Wellington, New Zealand.
³ Department of Microbiology and Immunology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
⁴ Department of Microbiology and Immunology, University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
⁵ Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD, USA.
⁶ Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand.
⁷ WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC, Australia.
⁸ Webster Centre for Infectious Diseases, University of Otago, Dunedin, New Zealand.

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.

Keywords: Immunology; Virology.