The impact of seasonal coronavirus immunity on susceptibility to SARS-CoV-2 infection and COVID-19 vaccination

In a recent study posted to the bioRxiv* preprint server, researchers investigated whether immunity against seasonal human coronavirus (CoV) spike (S) proteins of HKU1, OC43, NL63, or 229E could protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. They also investigated the impact of pre-existing immune levels against seasonal CoV S on the immune protection conferred by messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccinations.

Background

Seasonal CoVs have widely circulated among humans for several years. With advancing age, the likelihood of viral exposures and the generation of immunity against them increases. Researchers have hypothesized that anti-seasonal CoV immunity could partially protect against COVID-19 and that SARS-CoV-2 vaccinations induce back-boosting effects against the seasonal β-CoV S proteins. However, the effects of anti-seasonal CoV immunity on SARS-CoV-2 infection susceptibility and COVID-19 mRNA vaccinations are unclear.

About the study

In the present study, researchers evaluated the immune protective effects of anti-seasonal CoV S immunity against COVID-19-causing SARS-CoV-2 in mice and whether the pre-existing immune levels to seasonal CoVs impacted the immune protection conferred by SARS-CoV-2 vaccinations.

Mice were vaccinated with NL63, 229E, OC43, HKU1, and SARS-CoV-2 S proteins in prime-boost regimens. For comparison, control mice received influenza-causing virus HA (hemagglutinin) antigen vaccinations. After 28 days of booster vaccinations, immunological responses among the animals were measured using enzyme-linked immunosorbent assays (ELISA).

In addition, mice sera were assessed by ADCC (antibody-dependent cellular cytotoxicity) reporter assays. After 21 days of booster vaccinations, mice were intranasally transduced with non-replicating adenovirus-expressing hACE2 (human angiotensin-converting enzyme 2) followed by SARS-CoV-2 wild-type (wt) Washington-1 strain challenge after five days.

Mice were euthanized after three days and five days of SARS-CoV-2 to obtain their pulmonary tissues for viral load quantification by classic plaque assays, and their antibody titers were determined. Further, mice were vaccinated 21 days post-boost with a SARS-CoV-2 S-encoded LNP (lipid nanoparticle)-formulated and nucleoside-modified mRNA vaccine encoding the SARS-CoV-2 S. An unvaccinated control group was added for comparative evaluation. Vero E6 cells were used for cell culture experiments, and neutralization assays were performed.

Results

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Seasonal CoV S induced robust and targeted immunological responses among the animals with considerable alpha-CoV and beta-CoV cross-reactivity. Pre-existing seasonal CoV S immunity provided negligible immune protection against SARS-CoV-2 but did not show any negative effects on vaccination-induced anti-SARS-CoV-2 immunity.

229E S-vaccinated mice sera reacted robustly with 229E S, whereas activity against NL63 S was lowered, and no activity was observed among the three beta-CoV S. NL63 S appeared to be marginally less immunogenic and generated comparable titers indicating strong activity against the homologous S, lesser reactivity to 229E S and some, although lowered reactivity to β-CoV S.

OC43 vaccination induced robust anti-OC43 S activity, lower activity for HKU-1 S and SARS-CoV-2, and negligible activity for α-CoVs. HKU1 S vaccination led to strong activity for the homologous S and lesser titers for SARS-CoV-2 S and OC43. SARS-CoV-2 S vaccination induced high reactivity for the homologous S with little cross-reactivity for HKU-1 and OC43 but no α-CoV S reactivity. SARS-CoV-2 S-vaccinated mice were the only animals that showed protection from the viral challenge.

High SARS-CoV-2 S levels were observed among all the seasonal coronaviruses’ S-vaccinated animals at comparable levels as in controls. No mice exhibited overt illness after challenge, and serological titers against SARS-CoV-2 S titers among all the seasonal coronavirus S-vaccinated animals were significantly elevated with a similar elevation among controls.

SARS-CoV-2 S-vaccinated mice titers did not show any increases after infection, indicative of sterilizing immune responses, and negligible back-boosting to seasonal CoV S was observed. The vaccination led to high neutralization and binding antibody titers against the S proteins of SARS-CoV-2 among all the groups, with the greatest titers among SARS-CoV-2 S-vaccinated animals and lesser titers among those vaccinated with HA or seasonal CoV S.

The similarity in titers among mice vaccinated with the S proteins of seasonal coronaviruses and HA antigens of the influenza virus indicated no detrimental effects on immunological responses to SARS-CoV-2 mRNA-LNP vaccines. No viral organisms were detected in mRNA-LNP-immunized mice on the third day or fifth-day post-challenge; however, increased titers were observed among completely naïve mice. The findings indicated that a fraction of SARS-CoV-2 S-vaccinated mice were active against cellular surface-expressed S proteins. However, serum samples of seasonal CoV S-vaccinated animals did not show activity except for two HKU1 responders.

Conclusion

Overall, the study findings showed that seasonal CoV S-vaccinated mice S proteins did not exhibit any added immune protection compared to controls against SARS-CoV-2. A negligible back-boosting effect was observed against β-CoV S post-SARS-CoV-2 infection; however, no negative original antigenic sin-like effects were observed on the SARS-CoV-2 mRNA vaccination-induced immunological responses among mice with pre-existing anti-seasonal CoV S immunity.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.