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

In a recent study posted on Bio Rxiv*Preprint server, researchers found that immunity to the seasonal human coronavirus (CoV) spike (S) protein of HKU1, OC43, NL63, or 229E is associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) We investigated whether it is possible to protect against in vitroThey also investigated the impact of pre-existing immunity levels against seasonal CoV S on the immune protection conferred by messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination.

Background

Seasonal CoV has been circulating widely among humans for several years. As we age, the likelihood of exposure to viruses and the development of immunity to them increases. Researchers hypothesized that anti-seasonal CoV immunity may partially protect against COVID-19 and that SARS-CoV-2 vaccination induces a back-boost effect on the seasonal β-CoV S protein. is standing However, the impact of anti-seasonal CoV immunity on SARS-CoV-2 infection susceptibility and COVID-19 mRNA vaccination is unknown.

About research

In the present study, the researchers demonstrated the immunoprotective effect of anti-seasonal CoV S immunity against SARS-CoV-2, which causes COVID-19 in mice, and that pre-existing levels of immunity against seasonal CoV contribute to the immune protection conferred by SARS. Evaluate whether it will have an impact. CoV-2 vaccination.

Mice were vaccinated with NL63, 229E, OC43, HKU1 and SARS-CoV-2 S protein in a prime-boost regimen. For comparison, control mice were vaccinated with the influenza-causing virus HA (hemagglutinin) antigen. Twenty-eight days after booster vaccination, immune responses among animals were measured using an enzyme-linked immunosorbent assay (ELISA).

Additionally, mouse sera were evaluated by ADCC (Antibody Dependent Cytotoxicity) reporter assay. After 21 days of booster vaccination, mice were intranasally transduced with non-replicating adenovirus-expressing hACE2 (human angiotensin-converting enzyme 2) and 5 days later were challenged with SARS-CoV-2 wild-type (wt) Washington-1 strain. I was.

Mice were euthanized 3 and 5 days after SARS-CoV-2 and lung tissue was harvested. viral load Quantification by classical plaque assay and their antibody titers were determined. In addition, 21 days after his boost, mice were vaccinated with LNP (lipid nanoparticle) formulations encoding SARS-CoV-2 S and nucleoside-modified mRNA vaccines encoding SARS-CoV-2 S. evaluation. Vero E6 cells were used for cell culture experiments and neutralization assays were performed.

result

Seasonal CoV S elicited robust and targeted immune responses among 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 adversely affect anti-SARS-CoV-2 immunity from vaccination.

Sera from 229ES vaccinated mice reacted strongly with 229ES, but had reduced activity against NL63 S and no activity was observed among the three beta-CoV S. It is less reactive to congeners S, 229E S and some, but less reactive to β-CoV S .

OC43 vaccination induced strong anti-OC43 S activity, lower activity against HKU-1 S and SARS-CoV-2, and negligible activity against α-CoV. HKU1 S vaccination resulted in strong activity against allogeneic S and low titers against SARS-CoV-2 S and OC43. SARS-CoV-2 S vaccination induced high reactivity to the homologous S and little cross-reactivity to HKU-1 and OC43, but no α-CoV S reactivity. Mice vaccinated with SARS-CoV-2 S vaccine were the only animals that showed protection from virus challenge.

High S levels of SARS-CoV-2 were observed in all seasonal infections. coronavirus• Animals vaccinated at levels comparable to controls. None of the mice showed overt illness after challenge, and serological titers against SARS-CoV-2 S titers in all seasonal coronavirus S vaccinated animals were significantly elevated with similar increases among controls. did.

We observed that titers of mice vaccinated with SARS-CoV-2 S vaccine showed no increase after infection, indicating sterilizing the immune response, and negligible back-boost to seasonal CoV S it was done. Vaccination resulted in higher neutralizing and binding antibody titers to the S protein of SARS-CoV-2 in all groups, with the highest titers in SARS-CoV-2 S-vaccinated animals, HA or seasonal Animals inoculated with sexual CoV had lower titers of S.

Similarity of titers between mice vaccinated with seasonal coronavirus S protein and HA antigen Influenza virus studies have shown no detrimental effects on immune responses to the SARS-CoV-2 mRNA-LNP vaccine. No viral organisms were detected in mRNA-LNP-immunized mice 3 or 5 days after challenge. However, elevated titers were observed in completely naïve mice. The findings showed that some mice vaccinated with the SARS-CoV-2 S vaccine were active against the cell surface expressed S protein. However, serum samples from seasonal CoV S-vaccinated animals showed no activity except for two HKU1 responders.

Conclusion

Overall, the study results showed that S protein in seasonal CoV S-vaccinated mice showed no additional immune protection compared to controls against SARS-CoV-2 infection. A negligible backboosting effect was observed for later β-CoV S. However, in mice with pre-existing anti-seasonal CoV S immunity, the original antigenic sin-like negative effect on the immunological responses induced by SARS-CoV-2 mRNA vaccination is not observed.

*Important Notices

bioRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .