A new pan-sarbecovirus vaccine candidate neutralizes Omicron BQ.1.1 and XBB subvariants

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In a recent article published in the journal PNASresearchers in China provide evidence that a new vaccine candidate known as CF501/RBD-Fc potently neutralized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BQ.1.1 and XBB in a rhesus animal model.

This vaccine included the human immunoglobulin G (hIgG) fraction, crystallizable (Fc)-conjugated receptor binding domain (RBD) from the SARS-CoV-2 ancestral strain WA1, in combination with a novel stimulator of interferon genes (STING)- agonist-based adjuvant called CF501. The study findings confirm that CF501/RBD-Fc induced highly potent and sustained broad-neutralizing antibody (bnAb) responses against several SARS-CoV-2 variants, including Omicron subvariants.

Study: An RBD-based pan-sarbecovirus vaccine from the original SARS-CoV-2 strain elicits potent neutralizing antibodies against XBB in non-human primates. Image credit: MemoryMan/Shutterstock.com

Background

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

Previous studies using the pseudovirus neutralization test have shown that, compared to the ancestral strain D614G, XBB is up to 155 times more resistant to nAbs in sera from vaccinees. Thus, there remains an urgent need for a pan-sarbecovirus vaccine with the ability to neutralize current and emerging SARS-CoV-2 variants.

About the study

In the current study, researchers administered three doses of CF501/RBD-Fc or Alum/RBD-Fc-based vaccines into two groups, each consisting of three rhesus monkeys. Sera was then collected to evaluate RBD-binding IgG and nAb titers by 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 animal were correlated by pairwise comparisons to assess the association between nAb and binding antibodies specific for Omicron subvariants XBB and BQ.1.1.

Results

At day 28, after two vaccine doses, endpoint RBD-specific IgG titers against Omicron subvariants in the CF501/RBD-Fc group ranged between 512,000 and 1,792,000. These values ​​were almost three to 28 times higher than those of the Alum/RBD-Fc group.

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 magnitude of RBD binding antibodies remained consistently higher in the CF501/RBD-Fc group after three vaccine doses and remained high until day 191 after the first vaccination.

The 50% neutralizing titers (NT50) of bnAbs in CF501/RBD-Fc macaque sera were much higher than those in the Alum/RBD-Fc group against all pseudotyped viruses, with NT50 values ​​of 436 and 313 against BQ.1.1 and XBB, 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, respectively, against BQ.1.1 and XBB after receiving the first vaccine dose .

These titers also increased in the Alum/RBD-Fc group after three vaccine doses; however, these values ​​increased marginally from BQ.1.1 and XBB. Finally, NT50 values ​​decreased in both groups. The third vaccine dose did not cause elevated 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, respectively, relative to D614G, these bnAbs effectively neutralized BQ.1.1 and XBB infection. The results of the virus neutralization test also showed that CF501/RBD-Fc sera potently neutralized authentic BA.2.2 infection compared to Alum/RBD-Fc sera. The immunofluorescence test also confirmed that sera from the CF501/RBD-Fc group potently inhibited the replication of Omicron BA.2.2.

Conclusions

Overall, the study findings indicate that the CF501 adjuvant stimulated conservative but non-dominant RBD epitopes for generation of bnAbs against pan-sarbecovirus vaccines. Therefore, the researchers recommend replacing the adjuvant in the first-generation COVID-19 subunit vaccines with CF501 for next-generation booster vaccinations. This strategy can enhance immune responses against SARS-CoV-2 Omicron subvariants BQ.1.1 and XBB, as well as future SARS-CoV-2 variants yet to emerge.

Magazine reference:

  • Liu, Z., Zhou, J., Wang, X., et al. (2023). An RBD-based pan-sarbecovirus vaccine from the original SARS-CoV-2 strain elicits potent neutralizing antibodies against XBB in non-human primates. PNAS. doi:10.1073/pnas.2221713120

Written by

No Matur

Neha is a digital marketing professional based in Gurugram, India. She holds a master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in preclinical research as part of her research project in the Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.

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    Mathur, Neha. (2023, March 16). A new pan-sarbecovirus vaccine candidate neutralizes Omicron BQ.1.1 and XBB subvariants. 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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