Study demonstrates robust antibody response elicited by trivalent protein subunit vaccine against SARS-CoV-2

In a recent study published on bioRxiv* preprint server, researchers demonstrated that a trivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine enhanced the extent of humoral immune responses in mice.

Background

SARS-CoV-2 vaccines have reduced morbidity and mortality from coronavirus disease 2019 (COVID-19). Nonetheless, emerging variants of SARS-CoV-2 and global inequities in vaccination have deprived many low- and middle-income countries of access to variant-appropriate vaccines.

Protein subunit vaccine the technology is conducive to equitable global distribution given the relatively low cost of production, thermostability and high safety profile. There is growing interest in vaccines that can target multiple variants. A multivalent vaccine is a conventional approach to augment the antigenic landscape against ever-evolving pathogens.

The study and the conclusions

In the current study, researchers evaluated the immunogenicity of protein subunit vaccines based on the S1 spike of the wild-type SARS-CoV-2, Delta, or Omicron variant administered to mice in individual monovalent form. antigens or a trivalent vaccine incorporating all three antigens. Recombinant SARS-CoV-2 Wuhan, Delta and Omicron BA.1 S1 subunits peak proteins have expressed themselves.

Polyclonal anti-spike antibodies recognized recombinant antigens in Western blot. BALB/c female mice were immunized with SARS-CoV-2 Wuhan-S1, Delta-S1, Omicron-S1 or a trivalent vaccine incorporating these antigens. The animals received a homologous boost three weeks later. Serum samples were obtained before and after 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 titers (EPTs) against Wuhan S1 at week 5 compared to week 3.

Interestingly, mice primed with the Wuhan S1 vaccine showed lower EPTs at week 9 than the others. Mice receiving the trivalent vaccine showed higher EPTs at weeks 3, 5, and 7 against Wuhan S1 than those vaccinated with the Omicron S1 vaccine. Mice vaccinated with Delta S1 or the trivalent vaccine showed the highest EPT geometric means against Delta S1 at week 3.

However, only those vaccinated with Omicron S1 or the trivalent vaccine showed higher EPTs against Delta S1 at week 5 compared to week 3. Animals receiving Delta S1, Omicron S1 or the trivalent vaccine had significantly higher EPTs against Omicron S1 at week 5 than at week 3 Omicron S1 and trivalent vaccines elicited the highest EPTs against Omicron S1 from week 3 to week 20.

Competitive immunoassays measuring inhibition of binding between SARS-CoV-2 spike and angiotensin-converting enzyme 2 (ACE2) correlate well with virus neutralization assays. Such assays are convenient substitutes for quantifying the neutralizing capacity of vaccinated sera. As such, the authors assessed the neutralizing ability of vaccine-induced antibodies to inhibit spike-ACE2 binding using spike proteins of different variants.

Sera from vaccinated mice were evaluated at weeks 5 and 7. Antibodies inhibiting spike-ACE2 binding were present in all vaccinated mice. Sera from mice vaccinated with Wuhan S1 showed the lowest median binding inhibition against spikes of Wuhan, Alpha, Beta, and Delta variants of SARS-CoV-2, while sera from mice vaccinated with Delta S1 showed inhibition robust against these variants.

However, sera immunized with Delta S1 had a weakened response against Omicron and its sublines. Mice vaccinated with Omicron S1 showed moderate to high binding inhibition against all spikes tested and showed potent inhibitory activity against Omicron spikes.

Mice immunized with the trivalent vaccine showed increased binding inhibition against all peaks tested compared to animals vaccinated with the monovalent counterparts. Additionally, trivalent vaccine recipients had higher median binding inhibition than Omicron S1 recipients against Wuhan, Alpha, Beta, Delta, and Omicron spikes (BA.1 and BA.2).

Finally, the authors plotted the mean values ​​of Wuhan, Delta, and Omicron peak binding IgG EPTs with percent binding inhibition. Delta S1 and trivalent vaccine recipients were clustered with the highest mean IgG EPTs and binding inhibition against Wuhan and Delta spikes. Mice immunized with Omicron S1 and trivalent vaccine exhibited the highest mean IgG EPTs and binding inhibition.

conclusion

In summary, researchers observed robust antibody responses using SARS-CoV-2 spike S1 subunit vaccines in mice. All vaccinated animals showed strong binding IgG responses against Wuhan, Delta and Omicron S1. Specifically, recipients of the trivalent vaccine showed cross-reacting antibodies inhibiting the ACE2 spike with an increased magnitude compared to their monovalent counterparts.

These results indicated that increasing the valence of COVID-19 vaccines might not necessarily attenuate the magnitude of immune responses against individual variants. The results support the use of the trivalent COVID-19 vaccine incorporating the S1 spike subunit of SARS-CoV-2 variants Wuhan, Delta, and Omicron to increase antigen coverage and augment immune responses.

*Important Notice

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