Pre-existing anti-HCoV-OC43 immunity influences the durability and cross-reactivity of humoral response to SARS-CoV-2 vaccination

Abstract

PurposeThis study was conducted in order to properly understand whether prior seasonal human coronavirus (HCoV) immunity could impact the potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for future outbreaks.MethodsWe performed enzyme-linked immunosorbent assay (ELISA) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E), and ELISA [anti-RBD and anti-nucleoprotein (N)], chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test, and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees.ResultsWe found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. A further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positively correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at 12 and 24 weeks after the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies.ConclusionOur data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals, and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.

Memory SARS-CoV-2 T-cell response in convalescent COVID-19 patients with undetectable specific IgG antibodies: a comparative study

“…Cross-reactivity could be related to previous immunization against common cold coronavirus infections. Although we did not find a relationship between in vitro T-cell reactivity against SARS-CoV-2 peptides in healthy controls and T-cell response against HCoV-229E, we cannot rule out the possibility that proliferation against other common coronaviruses such as HCoV-OC43, HCoV-NL63, HCoV-HKU1 may exist in controls ( 18 , 23 ). Nevertheless, despite cross-reactivity, proliferative response had a good ability to discriminate between individuals with resolved infection and unexposed individuals.…”

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy

“…Despite an overall low response, NtAb titers to BA.5 varied over three orders of magnitude. This might reflect the inclusion of subjects with an undiagnosed prior SARS-CoV-2 infection and/or higher cross-reactivity due to prior exposure to seasonal human coronaviruses [31]. The latter could explain the positive correlation between BA.5 NtAb titers and patient age detected in our case file, but this is a hypothesis that needs to be confirmed on a larger number of patients.…”

Unravelling Antigenic Cross-Reactions toward the World of Coronaviruses: Extent of the Stability of Shared Epitopes and SARS-CoV-2 Anti-Spike Cross-Neutralizing Antibodies

“…Che and colleagues [ 45 ] found that sera from SARS-CoV-1 showed a several fold increase in antibody titers against HCoV-229E and HCoV-OC43 compared to controls. Hu and colleagues [ 47 ] reported that preexisting antibodies to HCoV-OC43 in healthy people were positively correlated with an immune response against the receptor binding domain (RBD) found in the S protein of SARS-CoV-2 and neutralization antibodies to SARS-CoV-2 in people who had been vaccinated against SARS-CoV-2. The alignment of these coronaviruses S protein sequences suggested possible cross-reactive immunity against peptides 319 -RVQPTESTIVRFP, 332 -ITNLCPFGEVF, 358 -ISNCVADYSVLYNSA, 374 -FSTFKCYGVSPT, 388 -NDLCFTNVYADSFVIRG, 407 -VRQIAP, 429 -FTGCVIAW, 450 -NYLYRLFR, 470 -TEIYQAGS, 504 -GYQPYRVVVLSFELL, and 535 -KNKCVNF, some of which (e.g., 407 -VRQIAP) had been previously identified as SARS-CoV-2 spike protein S1 subunit (S1) linear B cell epitopes [ 48 , 49 ].…”

“…Unsurprisingly, due to the sequence identities or similarities of proteins between the different coronaviruses, the literature reports a large number of cases of cross-reactions between different coronaviruses and SARS-CoV-2, and it is broadly distributed across the viral proteome, including the spike protein with recognition of the spike RBD [ 47 , 50 , 52 , 57 , 132 , 133 , 134 ]. What appears less clearly is the frequency of people who had probably never been exposed to SARS-CoV-2 and who have cross-immunity to SARS-CoV-2 pre-existing their infection or vaccination.…”