Longitudinal analysis of SARS-CoV-2 reinfection reveals distinct kinetics and emergence of cross-neutralizing antibodies to variants of concern

Antonio Facciuolo; Jill Van Kessel; Andrea Kroeker; Mingmin Liao; Jocelyne M Lew; Darryl Falzarano; Alyson A Kelvin; Volker Gerdts; Scott Napper

doi:10.3389/fmicb.2023.1148255

Longitudinal analysis of SARS-CoV-2 reinfection reveals distinct kinetics and emergence of cross-neutralizing antibodies to variants of concern

Front Microbiol. 2023 Mar 29:14:1148255. doi: 10.3389/fmicb.2023.1148255. eCollection 2023.

Authors

Antonio Facciuolo^{1

2}, Jill Van Kessel¹, Andrea Kroeker¹, Mingmin Liao¹, Jocelyne M Lew¹, Darryl Falzarano^{1

2}, Alyson A Kelvin^{1

3}, Volker Gerdts^{1

2}, Scott Napper^{1

3}

Affiliations

¹ Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, Saskatoon, SK, Canada.
² Department of Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK, Canada.
³ Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.

Abstract

The ongoing evolution of SARS-CoV-2 continues to raise new questions regarding the duration of immunity to reinfection with emerging variants. To address these knowledge gaps, controlled investigations in established animal models are needed to assess duration of immunity induced by each SARS-CoV-2 lineage and precisely evaluate the extent of cross-reactivity and cross-protection afforded. Using the Syrian hamster model, we specifically investigated duration of infection acquired immunity to SARS-CoV-2 ancestral Wuhan strain over 12 months. Plasma spike- and RBD-specific IgG titers against ancestral SARS-CoV-2 peaked at 4 months post-infection and showed a modest decline by 12 months. Similar kinetics were observed with plasma virus neutralizing antibody titers which peaked at 2 months post-infection and showed a modest decline by 12 months. Reinfection with ancestral SARS-CoV-2 at regular intervals demonstrated that prior infection provides long-lasting immunity as hamsters were protected against severe disease when rechallenged at 2, 4, 6, and 12 months after primary infection, and this coincided with the induction of high virus neutralizing antibody titers. Cross-neutralizing antibody titers against the B.1.617.2 variant (Delta) progressively waned in blood over 12 months, however, re-infection boosted these titers to levels equivalent to ancestral SARS-CoV-2. Conversely, cross-neutralizing antibodies to the BA.1 variant (Omicron) were virtually undetectable at all time-points after primary infection and were only detected following reinfection at 6 and 12 months. Collectively, these data demonstrate that infection with ancestral SARS-CoV-2 strains generates antibody responses that continue to evolve long after resolution of infection with distinct kinetics and emergence of cross-reactive and cross-neutralizing antibodies to Delta and Omicron variants and their specific spike antigens.

Keywords: COVID-19; Delta (B.1.617.2); Omicron (BA.1); SARS-CoV-2 reinfection; cross-neutralizing antibodies; duration of immunity.

Grants and funding

This study was supported by Canadian Institutes of Health Research funding (OV5-170349) to DF and Innovation Saskatchewan, Government of Saskatchewan. VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility (InterVac).