Pre-Existing Cross-Reactive Antibody Responses Do Not Significantly Impact Inactivated COVID-19 Vaccine-Induced Neutralization

Abstract

Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% vs. 12.0% ± 2.2%, P=0.990) and post-vaccination (43.8% ± 25.1% vs. 44.6% ± 21.5%, P=0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.

Effect of seasonal coronavirus immune imprinting on the immunogenicity of inactivated COVID-19 vaccination

“…Given the wide spread of sCoVs among the populations, we investigated whether prior sCoVs infection would impact the immunogenicity of the inactivated COVID-19 vaccine. Consistent with one previous study ( 36 ), our findings indicated that sCoVs antibody levels scarcely affected the neutralizing antibody titer induced by the inactivated vaccine, suggesting that immune imprinting induced by prior sCoVs infection did not appear to be a major factor affecting the immunogenicity of inactivated COVID-19 vaccine. This may be attributed to the distribution of cross-reactive epitopes between sCoVs and SARS-CoV-2, as pre-existing cross-reactive antibodies triggered by sCoVs infections primarily target non-neutralizing sites of SARS-CoV-2 ( 19 , 30 ).…”

Pre‐existing immunity to SARS‐CoV‐2 associates with strong T cell responses induced by inactivated COVID‐19 vaccines

“…Our results indicated that pre‐existing antibodies, viral protein‐binding B cells, breadth of B cell epitopes, or spike‐specific CD4 + T cells had little impact on the inactivated vaccine‐induced neutralization. Consistently, a previous report on inactivated COVID‐19 vaccines showed that pre‐existing B cell responses detected by mapping B cell epitopes covering the whole sequence of SARS‐CoV‐2 did not significantly affect the neutralizing activity 35 . These results indicate that inactivated‐vaccine‐induced humoral immunity may poorly benefit from pre‐existing immunity to SARS‐CoV‐2.…”

“…Consistently, a previous report on inactivated COVID-19 vaccines showed that pre-existing B cell responses detected by mapping B cell epitopes covering the whole sequence of SARS-CoV-2 did not significantly affect the neutralizing activity. 35 These results indicate that inactivatedvaccine-induced humoral immunity may poorly benefit from preexisting immunity to SARS-CoV-2.…”

Pathogen Discovery in the Post-COVID Era

“…Depending on the material of the slide carrier, the array can accommodate from a range of from thousands to three million distinct linear peptides. This approach has greatly enhanced the assay sensitivity, enabling early diagnosis of diseases for Lyme disease, Acute Flaccid Myelitis, and others [47][48][49][50]. Another technique, VirScan, integrates high-throughput DNA oligo synthesis, bacteriophage display, and nextgeneration sequencing to achieve antibody profiling.…”