New pan-sarbecovirus vaccine candidate neutralizes Omicro’s BQ.1.1 and XBB subvariants

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In an article published in a recent newspaper PNASChinese researchers have presented evidence that a new vaccine candidate known as CF501/RBD-Fc effectively neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BQ.1.1 and XBB in a rhesus macaque animal model.

This vaccine contained the human immunoglobulin G (hIgG) fraction, the crystallizable (Fc)-conjugated receptor-binding domain (RBD) of the WA1 strain carrying SARS-CoV-2 together with a novel stimulator of interferon genes (STING) agonist. based adjuvant called CF501. The study results confirm that CF501/RBD-Fc induces highly potent and persistent broad-spectrum antibody (bnAb) responses against multiple SARS-CoV-2 variants, including Omicron subvariants.

Research: A Sarbecovirus vaccine based on the RBD of the original SARS-CoV-2 strain elicits potent neutralizing antibodies against XBB in primates. Image credit: MemoryMan / Shutterstock.com

Background

Due to their exceptional immune response properties, Omicron subvariants pose a significant challenge to current coronavirus disease 2019 (COVID-19) vaccines. For example, the BA.5 subvariant is resistant to neutralization even after four doses of ribonucleic acid (mRNA) vaccine. Furthermore, the newly generated XBB Omicron subvariant remains unneutralized by nAbs induced by a booster dose of a bivalent vaccine containing Omicron BA.5 mRNA sequences and progenitor spike (S) proteins.

Previous studies using a pseudovirus neutralization assay have shown that compared to the ancestral strain D614G, XBB is up to 155-fold more resistant to nAbs in vaccine serum. Thus, there is still an urgent need for a pan-sarbecovirus vaccine capable of neutralizing current and emerging SARS-CoV-2 variants.

About the study

In this study, researchers administered three doses of CF501/RBD-Fc or Aluna/RBD-Fc-based vaccines to two groups of three rhesus macaques each. Subsequently, sera were collected to assess RBD-binding IgG and nAb titers using enzyme-linked immunosorbent assay (ELISA) and virus neutralization assays.

The researchers also tested whether sera from immunized rhesus macaques could neutralize pseudotyped Omicron subvariants. The parameters of each experimental animal were correlated by pairwise comparisons to assess the association between the nAb and binding antibodies specific for the Omicron subvariants XBB and BQ.1.1.

Score

At day 28, after two vaccine doses, endpoint RBD-specific IgG titers against Omicron subvariants in the CF501/RBD-Fc group ranged from 512,000 to 1,792,000. These values ​​were nearly 3- to 28-fold higher than those in the Alum/RBD- Fc group values.

Although endpoint titers gradually decreased, they remained relatively stable and higher in the CF501/RBD-Fc group compared to the Alum/RBD-Fc group. The number of RBD-binding antibodies remained consistently higher in the CF501/RBD-Fc group after three doses of vaccine and remained high until day 191 after the first vaccination.

The 50% neutralizing titers (NT50) of bnAbs from sera from CF501/RBD-Fc macaques were much higher than those from the Alum/RBD-Fc group against all pseudotyped viruses, with NT50 values ​​of 436 and 313 for BQ.1.1 and XBB against respectively at day 28. Cross-neutralizing bnAb titers in the CF501/RBD-Fc group continued to increase after the third vaccination, with day 122 NT50 values ​​of 2,118 and 2,526 against BQ.1.1 and XBB, respectively, after receiving the first dose of vaccine.

These titers also increased in the Alum/RBD-Fc group after three vaccine doses; however, these values ​​increased slightly against BQ.1.1 and XBB. Finally, NT50 values ​​decreased in both groups. The third vaccine dose did not increase NT50 titers against D614G, but dramatically increased bnAb titers against the Omicron subvariants.

Although their NT50 against BQ.1.1 and XBB decreased by 26.9- and 22.5-fold compared to D614G, these bnAbs efficiently neutralized BQ.1.1 and XBB infection. The results of the virus neutralization assay also showed that CF501/RBD-Fc sera efficiently neutralized authentic BA.2.2 infection compared to Alum/RBD-Fc sera. Immunofluorescence assay also confirmed that the CF501/RBD-Fc group sera effectively inhibited the replication of Omicron BA.2.2.

Conclusions

Overall, the study results show that the CF501 adjuvant stimulates conservative but non-dominant RBD epitopes to produce bnAbs against pan-sarbecovirus vaccines. Therefore, the researchers recommend that the adjuvant of the first-generation COVID-19 subunit vaccines be replaced with CF501 in the next-generation booster vaccines. This strategy may enhance immune responses against SARS-CoV-2 Omicron subvariants BQ.1.1 and XBB, as well as future SARS-CoV-2 variants that have yet to emerge.

Journal reference:

  • Liu, Z., Zhou, J., Wang, X., et al. (2023). A Sarbecovirus vaccine based on the RBD of the original SARS-CoV-2 strain elicits potent neutralizing antibodies against XBB in primates. PNAS. doi: 10.1073/pnas.2221713120

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. He has completed his MS from University of Rajasthan with specialization in Biotechnology in 2008. He has experience in pre-clinical research as part of his research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. He also has a degree in C++ programming.

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    Mathur, Neha. (2023, March 16). A new pan-sarbecovirus vaccine candidate neutralizes the BQ.1.1 and XBB subvariants of Omicron. News-Medical. Retrieved March 17, 2023, from https://www.news-medical.net/news/20230316/A-novel-pan-sarbecovirus-vaccine-candidate-neutralizes-Omicron-BQ11-and-XBB-subvariants.aspx.

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    Mathur, Neha. “New pan-sarbecovirus vaccine candidate neutralizes Omicron BQ.1.1 and XBB subvariants”. News-Medical. March 17, 2023. .

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    Mathur, Neha. “New pan-sarbecovirus vaccine candidate neutralizes Omicron BQ.1.1 and XBB subvariants”. News-Medical. https://www.news-medical.net/news/20230316/A-novel-pan-sarbecovirus-vaccine-candidate-neutralizes-Omicron-BQ11-and-XBB-subvariants.aspx. (accessed 17 March 2023).

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    Mathur, Neha. 2023. New pan-sarbecovirus vaccine candidate neutralizes Omicro’s BQ.1.1 and XBB subvariants. News-Medical, accessed March 17, 2023, https://www.news-medical.net/news/20230316/A-novel-pan-sarbecovirus-vaccine-candidate-neutralizes-Omicron-BQ11-and-XBB-subvariants. aspx .

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