Studies Show Strong Antibody Responses Induced by Trivalent Protein Subunit Vaccines Against SARS-CoV-2

In a recent study posted on Bio Rxiv*Preprint Server, Researchers have demonstrated that a trivalent vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) improves the breadth of the humoral immune response in mice.

Background

SARS-CoV-2 vaccine reduced morbidity and mortality from coronavirus disease (COVID-19) in 2019. Nevertheless, the emergent SARS-CoV-2 variant and global vaccination inequities have deprived many low- and middle-income countries of access to vaccines tailored to the variant.

protein subunit vaccine The technology is advantageous for equitable global distribution due to its relatively low production cost, high thermal stability and high safety. There is growing interest in vaccines that can target multiple variants. Polyvalent vaccines are a traditional approach to enrich the antigenic landscape against ever-changing pathogens.

Research and Findings

In the present study, researchers evaluated the immunogenicity of protein subunit vaccines based on wild-type SARS-CoV-2, Delta, or Omicron variant spike S1 administered to mice as individual monovalent antigen or a trivalent vaccine that incorporates three antigens. Recombinant S1 subunits of SARS-CoV-2 Wuhan, Delta, and Omicron BA.1 spike protein expressed.

A polyclonal anti-spike antibody recognized the recombinant antigen in Western blots. Female Her BALB/c mice were immunized with SARS-CoV-2 Wuhan-S1, Delta-S1, Omicron-S1, or Her trivalent vaccines incorporating these antigens. Animals received a homologous booster 3 weeks after her. Serum samples were collected pre- and post-immunization.

Serum samples were serially diluted to measure immunoglobulin G (IgG) titers against SARS-CoV-2 Wuhan, Delta, and Omicron S1 using an enzyme-linked immunosorbent assay (ELISA). All vaccinated mice showed a significant increase in geometric mean IgG endpoint titers (EPT) against Wuhan S1 at week 5 compared to week 3.

Interestingly, Wuhan S1-vaccinated mice showed a lower EPT than other mice at 9 weeks. Mice receiving the trivalent vaccine had higher EPTs at weeks 3, 5 and 7 against Wuhan S1 than mice vaccinated with the Omicron S1 vaccine. Mice vaccinated with delta S1 or trivalent vaccines had the highest geometric mean EPT at 3 weeks to delta S1.

However, only animals vaccinated with Omicron S1 or trivalent vaccine showed higher EPT against delta S1 at week 5 compared to week 3. Omicron S1 and trivalent vaccines induced the highest EPT against Omicron S1 from weeks 3 to 20.

A competitive immunoassay measuring inhibition of binding between the SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2) correlates well with virus neutralization studies. Such assays are convenient surrogates for quantifying the neutralizing capacity of vaccinated sera. Therefore, the authors used different variants of the spike protein to assess its neutralizing ability to inhibit spike-ACE2 binding of vaccine-induced antibodies.

Sera from vaccinated mice were evaluated at 5 and 7 weeks. Antibodies that inhibit spike ACE2 binding were present in all vaccinated mice. Sera from Wuhan S1-vaccinated mice had the lowest median inhibition of binding to spikes from SARS-CoV-2 Wuhan, alpha, beta, and delta mutants, whereas sera from Delta S1-vaccinated mice showed It showed strong inhibition against these mutants.

However, Delta S1 immunized sera were attenuated in response to Omicron and its substrains. Mice vaccinated with Omicron S1 vaccine showed moderate to high inhibition of binding to all spikes tested and strong inhibitory activity against Omicron spikes.

Mice immunized with the trivalent vaccine showed enhanced inhibition of binding to all spikes tested compared to animals vaccinated with the monovalent vaccine. In addition, trivalent vaccinees had higher median inhibition of binding than Omicron S1 recipients to spikes from Wuhan, alpha, beta, delta, and Omicron (BA.1 and BA.2).

Finally, the authors plotted the mean values ​​of Wuhan, Delta, and Omicron spike-bound IgG EPTs with percent binding inhibition. Delta S1 and trivalent vaccinees were grouped with the highest mean IgG EPT and binding inhibition to Wuhan and Delta spike. Mice immunized with Omicron S1 and trivalent vaccines had the highest mean IgG EPT and binding inhibition.

Conclusion

In summary, researchers observed a strong antibody response when using the SARS-CoV-2 spike S1 subunit vaccine in mice. All vaccinated animals showed strong binding IgG responses to Wuhan, Delta and Omicron S1. Specifically, recipients of trivalent vaccines have a broader range of cross-reactive antibodies that inhibit ACE2 spikes compared to monovalent vaccines.

These results indicate that increasing the valency of COVID-19 vaccines may not necessarily attenuate the magnitude of immune responses to individual variants. This finding supports the use of his trivalent His COVID-19 vaccine, which incorporates the spike S1 subunit of SARS-CoV-2 Wuhan, Delta, and Omicron variants, to expand antigenic coverage and immunity. enhance the response.

*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