UB-612 vaccine booster discovered to elicit excessive neutralizing antibody ranges in opposition to SARS-CoV-2 Omicron

In a current examine posted to the bioRxiv* pre-print server, researchers evaluated the effectiveness of a novel vaccine candidate UB-612 in opposition to 14 extreme acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, together with the most recent variant of concern (VOC) Omicron.

Study: High neutralizing antibody levels against SARS-CoV-2 Omicron after UB-612 booster vaccination. Image Credit: natatravel/Shutterstock
Research: Excessive neutralizing antibody ranges in opposition to SARS-CoV-2 Omicron after UB-612 booster vaccination. Picture Credit score: natatravel/Shutterstock

Given the predictions that Omicron might substitute Delta VOC to develop into the dominant SARS-CoV-2 variant globally, it’s essential to discover vaccines with the power to counter its distinctive potential to evade the immune system.

Homologous or heterologous booster vaccines restore protecting neutralizing antibody (nAb) titers to ranges achieved by main immunization; nonetheless, research have evidenced that these titers lower 7.1-fold in opposition to Omicron than the ancestral D614G pressure. These findings increase issues about breakthrough infections in vaccinated people and spotlight the pressing have to administer COVID-19 booster doses globally.

Concerning the examine

Within the current examine, researchers evaluated the security profile and reactogenicity of the novel UB-612 vaccine candidate. Specifically, the nAb titers in opposition to Omicron elicited by its second and third dose (booster), and its reactivity to recombinant spike (S) and receptor-binding area (RBD) protein antigens of 14 SARS-CoV-2 variants.

To this finish, the staff analyzed sera samples from all of the contributors of the Part I trial and randomly chosen 84 contributors from the Part II trial of the UB-612 vaccine that happened in Vismederi, Siena, Italy. The 15 contributors of Part I trials acquired a 100-µg dose of UB-612 seven to 9 months after their two-dose main vaccination.

The analysis staff carried out enzyme-linked immunosorbent assays (ELISA) on sera samples of all of the examine contributors immunized with UB-612. ELISA detected the direct binding of immunoglobulin G (IgG) to recombinant S and RBD proteins; moreover, inhibition of binding to the human angiotensin-converting enzyme 2 (hACE2).

The researchers additionally established a vaccine efficacy (VE) prediction mannequin primarily based on the RBD exercise of IgG antibodies in opposition to the D614G pressure. They deployed it to foretell VE of UB-612 in opposition to symptomatic coronavirus illness 2019 (COVID-19).

Research findings

The UB-612 booster stimulated extremely cross-reactive IgG antibodies that successfully certain RBDs of 14 SARS-CoV-2 variants, together with Alpha, Beta, Gamma, Delta, and Omicron, a UB-612 characteristic primarily attributed to its RBD antigenic element.

The UB-612 booster elevated IgG binding titers in opposition to Omicron’s RBD by over 40-fold and in between 30-to 50-fold in opposition to different SARS-CoV-2 variants. After the UB-612 booster, the loss in neutralization titers in opposition to Omicron in comparison with the ancestral D614G pressure was considerably low. Accordingly, the nAb titer loss detected by a dwell virus assay was merely 1.4-fold, and that detected by a pseudovirus assay was 5.5-fold.

In comparison with the D614G pressure, the rise within the IgG titer ratio for Alpha, Beta, Delta, Gamma, and Omicron was 0.91-, 1.8-, 1.4-, 1.55-, and three.7-fold, respectively, after the booster dose of UB-612. The S-protein binding antibody responses additional confirmed the extent of stability within the ratios of ancestral to variant IgG antibodies elicited after the UB-612 booster dose.

Notably, the booster dose of UB-612 elevated ranges of S- and RBD-protein binding IgG antibodies and antibody geometric imply titers (GMTs) as a lot as a two-dose routine of the mRNA vaccines. Accordingly, the authors famous a 16- and a 13-fold improve in S- and RBD-protein binding IgG antibody ranges and GMTs of 2138 and 6767 (BAU/mL), respectively, in serum samples of Part I contributors boosted with UB-612.

Booster doses of the mRNA-1273, BNT162b2, or Ad26.COV.S vaccines elevated nAB titers in opposition to Omicron by 20- to 30-fold than for the ancestral pressure; nonetheless, the second and third dose of UB-612 elicited cross-reactive IgG antibodies and nAb in opposition to Omicron that remained secure over time. Furthermore, the UB-612 vaccine recalled a reminiscence B cell pool that produced nABs in opposition to conserved areas of RBDs of a number of SARS-CoV-2 variants.

The examine mannequin predicted 80% VE of a two-dose routine of UB-612 in opposition to the prototype pressure that spiked to 95% after its booster dose.

Conclusions

To summarize, a booster dose of UB-612, a novel vaccine candidate, not solely elicited sturdy IgG antibodies and nAb titers in opposition to 14 SARS-CoV-2 variants, together with Omicron, the magnitude of this immune response matched with different approved vaccines, together with mRNA-1273. UB-612 immunization additionally stimulated T-cell responses in opposition to conserved areas of S and RBDs of a number of variants.

Total, UB-612 emerged as a powerful COVID-19 booster vaccine, particularly in opposition to Omicron, with the potential to fight at present circulating and but to emerge SARS-CoV-2 variants.

*Vital discover

bioRxiv publishes preliminary scientific stories that aren’t peer-reviewed and, due to this fact, shouldn’t be considered conclusive, information scientific follow/health-related conduct, or handled as established data.

Journal reference:

  • Farshad Guirakhoo, Shixia Wang, Chang Yi Wang, Hui-Kai Kuo, Wen-Jiun Peng, Hope Liu, Lixia Wang, Marina Johnson, Adam Hunt, Mei Mei Hu, Thomas P. Monath, Alexander Rumyantsev, David Goldblatt. (2022). Excessive neutralizing antibody ranges in opposition to SARS-CoV-2 Omicron after UB-612 booster vaccination. bioRxiv. doi: https://doi.org/10.1101/2022.03.18.484436 https://www.biorxiv.org/content material/10.1101/2022.03.18.484436v1

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