Dynamics of neutralizing antibody titers in the months after SARS-CoV-2 infection

Abstract

Most individuals infected with SARS-CoV-2 develop neutralizing antibodies that target the viral spike protein. Here we quantify how levels of these antibodies change in the months following SARS-CoV-2 infection by examining longitudinal samples collected between ≈30 and 152 days post-symptom onset from a prospective cohort of 34 recovered individuals with asymptomatic, mild, or moderate-severe disease. Neutralizing antibody titers declined an average of about four-fold from one to four months post-symptom onset. Importantly, our data are consistent with the expected early immune response to viral infection, where an initial peak in antibody levels is followed by a decline to a lower plateau. Additional studies of long-lived B-cells and antibody titers over longer time frames are necessary to determine the durability of immunity to SARS-CoV-2.

Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

“…The ΔNA(RBD)-Flu virus stably maintains the gene encoding the RBD over multiple passages, and cells infected with this virus express high levels of RBD on their surface. Intranasal inoculation of mice with a single dose of ΔNA(RBD)-Flu elicits neutralizing antibodies against SARS-CoV-2 in mice, with titers comparable to those observed in humans following natural infection [33,43,44] or administration of two doses of a mRNA-based vaccine in clinical trials [20]. Notably, the ΔNA(RBD)-Flu elicited these neutralizing antibody titers after just a single intranasal inoculation at a viral dose that is lower than that typically used for live-attenuated influenza vaccines [4,13,45].…”

“…For cell surface expression studies, the protein sequence for SARS-CoV-2 Spike from (isolate Wuhan-1, Genbank NC_045512) was codon-optimized and contained a cytoplasmic tail truncation that removes the last 21 amino acids, as described previously [33]. Spike and the protein sequence for the membrane-anchored RBD in ∆NA(RBD) were each cloned into an expression plasmid (HDM) which places the gene under the control of a cytomegalovirus (CMV) promoter, to generate plasmids HDM-SARS2-Spike-delta21 [33] and HDM_Spike_RBD_B7-1 (Suppl. File 4).…”

“…We collected sera from the mice at 14-and 21-days post infection (dpi) and measured anti-SARS-CoV-2 titers using a Spike-pseudotyped lentivirus neutralization assay [33,35]. Neutralizing responses against SARS-Cov-2 were detected in mice infected with the ΔNA(RBD)-Flu at both 14and 21-dpi ( Fig 3C, curves available in Suppl.…”

Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

“…For cell surface expression studies, the protein sequence for the SARS-CoV-2 spike from (isolate Wuhan-1, Genbank NC_045512) was codon-optimized and contained a cytoplasmic tail truncation that removes the last 21 amino acids, as described previously [33]. Spike and the protein sequence for the membrane-anchored RBD in ∆NA(RBD) were each cloned into an expression plasmid (HDM) which places the gene under the control of a cytomegalovirus (CMV) promoter, to generate plasmids HDM-SARS2-Spike-delta21 [33] and HDM_Spike_RBD_B7-1 (File S4).…”

“…SARS-CoV-2 spike-pseudotyped lentivirus neutralization assays were performed as previously described [33,35], with slight modifications. The spike protein of SARS-CoV-2 that was used to produce pseudotyped lentivirus contained a cytoplasmic tail truncation that removes the last 21 amino acids [33]. Infections of 293T-ACE2 cells were performed in poly-L-lysine coated plates.…”