Durability and expansion of neutralizing antibody breadth following Ad26.COV2.S vaccination of mice

Shant H Mahrokhian; Lisa H Tostanoski; Catherine Jacob-Dolan; Roland C Zahn; Frank Wegmann; Katherine McMahan; Jingyou Yu; Makda S Gebre; Esther A Bondzie; Huahua Wan; Olivia Powers; Tianyi Ye; Julia Barrett; Hanneke Schuitemaker; Dan H Barouch

doi:10.1038/s41541-022-00454-4

Durability and expansion of neutralizing antibody breadth following Ad26.COV2.S vaccination of mice

NPJ Vaccines. 2022 Feb 23;7(1):23. doi: 10.1038/s41541-022-00454-4.

Authors

Shant H Mahrokhian^#^{1

2}, Lisa H Tostanoski^#¹, Catherine Jacob-Dolan^#^{1

3

4}, Roland C Zahn⁵, Frank Wegmann⁵, Katherine McMahan¹, Jingyou Yu¹, Makda S Gebre^{1

3}, Esther A Bondzie¹, Huahua Wan¹, Olivia Powers¹, Tianyi Ye^{1

3}, Julia Barrett¹, Hanneke Schuitemaker⁵, Dan H Barouch^{6

7

8

9}

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
² Tufts University School of Medicine, Boston, MA, 02111, USA.
³ Harvard Medical School, Boston, MA, 02115, USA.
⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA.
⁵ Janssen Vaccines & Prevention BV, Leiden, Netherlands.
⁶ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. dbarouch@bidmc.harvard.edu.
⁷ Harvard Medical School, Boston, MA, 02115, USA. dbarouch@bidmc.harvard.edu.
⁸ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, 02139, USA. dbarouch@bidmc.harvard.edu.
⁹ Massachusetts Consortium on Pathogen Readiness, Boston, MA, 02115, USA. dbarouch@bidmc.harvard.edu.

^# Contributed equally.

Abstract

Emerging SARS-CoV-2 variants with the potential to escape binding and neutralizing antibody responses pose a threat to vaccine efficacy. We recently reported expansion of broadly neutralizing activity of vaccine-elicited antibodies in humans 8 months following a single immunization with Ad26.COV2.S. Here, we assessed the 15-month durability of antibody responses and their neutralizing capacity to B.1.617.2 (delta) and B.1.351 (beta) variants following a single immunization of Ad26.COV2.S in mice. We report the persistence of binding and neutralizing antibody titers following immunization with a concomitant increase in neutralizing antibody breadth to delta and beta variants over time. Evaluation of bone marrow and spleen at 15 months postimmunization revealed that Ad26.COV2.S-immunized mice tissues contained spike-specific antibody-secreting cells. We conclude that immunization with Ad26.COV2.S elicits a robust immune response against SARS-CoV-2 spike, which expands over time to neutralize delta and beta variants more robustly, and seeds bone marrow and spleen with long-lived spike-specific antibody-secreting cells. These data extend previous findings in humans and support the use of a mouse model as a potential tool to further explore the dynamics of the humoral immune response following vaccination with Ad26.COV2.S.