tetano
Editor, Senior Moderator
iScience
. 2023 Feb 20;106256.
doi: 10.1016/j.isci.2023.106256. Online ahead of print.
Incorporation of SARS-CoV-2 spike NTD to RBD Protein Vaccine Improves Immunity Against Viral Variants
Isabelle Montgomerie[SUP] 1 [/SUP], Thomas W Bird[SUP] 1 [/SUP], Olga R Palmer[SUP] 2 [/SUP], Ngarangi C Mason[SUP] 2 [/SUP], Theresa E Pankhurst[SUP] 2 [/SUP], Blair Lawley[SUP] 3 [/SUP], Leonor C Hernández[SUP] 3 [/SUP], Rhodri Harfoot[SUP] 3 [/SUP], Astrid Authier-Hall[SUP] 2 [/SUP], Danielle E Anderson[SUP] 4 [/SUP], Kerry L Hilligan[SUP] 2 5 [/SUP], Kaitlin H Buick[SUP] 2 [/SUP], Naasson M Mbenza[SUP] 1 [/SUP], Gerd Mittelstädt[SUP] 6 [/SUP], Samara Maxwell[SUP] 1 [/SUP], Shubhra Sinha[SUP] 3 [/SUP], Joanna Kuang[SUP] 3 [/SUP], Kanta Subbarao[SUP] 4 7 [/SUP], Emily J Parker[SUP] 6 [/SUP], Alan Sher[SUP] 5 [/SUP], Ian F Hermans[SUP] 2 [/SUP], James E Ussher[SUP] 3 [/SUP], Miguel E Quiñones-Mateu[SUP] 3 8 [/SUP], Davide Comoletti[SUP] 1 [/SUP], Lisa M Connor[SUP] 1 2 [/SUP]; On behalf theVAANZ Group
Affiliations
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 (i) improved the magnitude and breadth of the T cell and anti-RBD response, and (ii) 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: ACE2, Angiotensin converting enzyme 2; AP, alkaline phosphatase; COVID-19; GC, germinal center; N terminal domain; NAbs, neutralizing antibodies; NTD, N terminal domain; RBD, Receptor binding domain; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; iLN, inguinal lymph nodes; receptor binding domain; vaccine.
. 2023 Feb 20;106256.
doi: 10.1016/j.isci.2023.106256. Online ahead of print.
Incorporation of SARS-CoV-2 spike NTD to RBD Protein Vaccine Improves Immunity Against Viral Variants
Isabelle Montgomerie[SUP] 1 [/SUP], Thomas W Bird[SUP] 1 [/SUP], Olga R Palmer[SUP] 2 [/SUP], Ngarangi C Mason[SUP] 2 [/SUP], Theresa E Pankhurst[SUP] 2 [/SUP], Blair Lawley[SUP] 3 [/SUP], Leonor C Hernández[SUP] 3 [/SUP], Rhodri Harfoot[SUP] 3 [/SUP], Astrid Authier-Hall[SUP] 2 [/SUP], Danielle E Anderson[SUP] 4 [/SUP], Kerry L Hilligan[SUP] 2 5 [/SUP], Kaitlin H Buick[SUP] 2 [/SUP], Naasson M Mbenza[SUP] 1 [/SUP], Gerd Mittelstädt[SUP] 6 [/SUP], Samara Maxwell[SUP] 1 [/SUP], Shubhra Sinha[SUP] 3 [/SUP], Joanna Kuang[SUP] 3 [/SUP], Kanta Subbarao[SUP] 4 7 [/SUP], Emily J Parker[SUP] 6 [/SUP], Alan Sher[SUP] 5 [/SUP], Ian F Hermans[SUP] 2 [/SUP], James E Ussher[SUP] 3 [/SUP], Miguel E Quiñones-Mateu[SUP] 3 8 [/SUP], Davide Comoletti[SUP] 1 [/SUP], Lisa M Connor[SUP] 1 2 [/SUP]; On behalf theVAANZ Group
Affiliations
- PMID: 36845030
- PMCID: PMC9940465
- DOI: 10.1016/j.isci.2023.106256
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 (i) improved the magnitude and breadth of the T cell and anti-RBD response, and (ii) 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: ACE2, Angiotensin converting enzyme 2; AP, alkaline phosphatase; COVID-19; GC, germinal center; N terminal domain; NAbs, neutralizing antibodies; NTD, N terminal domain; RBD, Receptor binding domain; SARS-CoV-2; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; iLN, inguinal lymph nodes; receptor binding domain; vaccine.