UB-612 vaccine booster found to elicit high neutralizing antibody levels against SARS-CoV-2 Omicron

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In a recent study posted to the bioRxiv* pre-print server, researchers evaluated the effectiveness of a novel vaccine candidate UB-612 against 14 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including the latest variant of concern (VOC) Omicron.

Study: High neutralizing antibody levels against SARS-CoV-2 Omicron after UB-612 booster vaccination. Image Credit: natatravel/Shutterstock

Given the predictions that Omicron could replace Delta VOC to become the dominant SARS-CoV-2 variant globally, it is crucial to explore vaccines with the ability to counter its exceptional potential to evade the immune system.

Homologous or heterologous booster vaccines restore protective neutralizing antibody (nAb) titers to levels achieved by primary immunization; however, studies have evidenced that these titers decrease 7.1-fold against Omicron than the ancestral D614G strain. These findings raise concerns about breakthrough infections in vaccinated individuals and highlight the urgent need to administer COVID-19 booster doses globally.

About the study

In the present study, researchers evaluated the safety profile and reactogenicity of the novel UB-612 vaccine candidate. In particular, the nAb titers against Omicron elicited by its second and third dose (booster), and its reactivity to recombinant spike (S) and receptor-binding domain (RBD) protein antigens of 14 SARS-CoV-2 variants.

To this end, the team analyzed sera samples from all the participants of the Phase I trial and randomly selected 84 participants from the Phase II trial of the UB-612 vaccine that took place in Vismederi, Siena, Italy. The 15 participants of Phase I trials received a 100-µg dose of UB-612 seven to nine months after their two-dose primary vaccination.

The research team performed enzyme-linked immunosorbent assays (ELISA) on sera samples of all the study participants immunized with UB-612. ELISA detected the direct binding of immunoglobulin G (IgG) to recombinant S and RBD proteins; additionally, inhibition of binding to the human angiotensin-converting enzyme 2 (hACE2).

The researchers also established a vaccine efficacy (VE) prediction model based on the RBD activity of IgG antibodies against the D614G strain. They deployed it to predict VE of UB-612 against symptomatic coronavirus disease 2019 (COVID-19).

Study findings

The UB-612 booster stimulated highly cross-reactive IgG antibodies that effectively bound RBDs of 14 SARS-CoV-2 variants, including Alpha, Beta, Gamma, Delta, and Omicron, a UB-612 feature primarily attributed to its RBD antigenic component.

The UB-612 booster increased IgG binding titers against Omicron’s RBD by over 40-fold and in between 30-to 50-fold against other SARS-CoV-2 variants. After the UB-612 booster, the loss in neutralization titers against Omicron compared to the ancestral D614G strain was significantly low. Accordingly, the nAb titer loss detected by a live virus assay was merely 1.4-fold, and that detected by a pseudovirus assay was 5.5-fold.

Compared to the D614G strain, the increase in the IgG titer ratio for Alpha, Beta, Delta, Gamma, and Omicron was 0.91-, 1.8-, 1.4-, 1.55-, and 3.7-fold, respectively, after the booster dose of UB-612. The S-protein binding antibody responses further confirmed the extent of stability in the ratios of ancestral to variant IgG antibodies elicited after the UB-612 booster dose.

Notably, the booster dose of UB-612 increased levels of S- and RBD-protein binding IgG antibodies and antibody geometric mean titers (GMTs) as much as a two-dose regimen of the mRNA vaccines. Accordingly, the authors noted a 16- and a 13-fold increase in S- and RBD-protein binding IgG antibody levels and GMTs of 2138 and 6767 (BAU/mL), respectively, in serum samples of Phase I participants boosted with UB-612.

Booster doses of the mRNA-1273, BNT162b2, or Ad26.COV.S vaccines increased nAB titers against Omicron by 20- to 30-fold than for the ancestral strain; however, the second and third dose of UB-612 elicited cross-reactive IgG antibodies and nAb against Omicron that remained stable over time. Moreover, the UB-612 vaccine recalled a memory B cell pool that produced nABs against conserved regions of RBDs of several SARS-CoV-2 variants.

The study model predicted 80% VE of a two-dose regimen of UB-612 against the prototype strain that spiked to 95% after its booster dose.

Conclusions

To summarize, a booster dose of UB-612, a novel vaccine candidate, not only elicited robust IgG antibodies and nAb titers against 14 SARS-CoV-2 variants, including Omicron, the magnitude of this immune response matched with other authorized vaccines, including mRNA-1273. UB-612 immunization also stimulated T-cell responses against conserved regions of S and RBDs of several variants.

Overall, UB-612 emerged as a strong COVID-19 booster vaccine, especially against Omicron, with the potential to combat currently circulating and yet to emerge SARS-CoV-2 variants.

*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.

Journal reference:

Source: News Medical


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