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

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

This vaccine included the human immunoglobulin G (hIgG) moiety, the crystallizable (Fc) conjugated receptor-binding domain of the ancestral SARS-CoV-2 strain WA1, in combination with a novel interferon gene enhancer ( STING) agonist-based adjuvant called CF501. Study results confirm that CF501/RBD-Fc induced highly potent and persistent broad neutralizing antibody (bnAb) responses against multiple SARS-CoV-2 variants, including Omicron subvariants.

Study: A pan-sarbecovirus vaccine based on the RBD of the original strain of SARS-CoV-2 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 vaccines against coronavirus disease 2019 (COVID-19). For example, the BA.5 subvariant is resistant to neutralization even after four doses of a messenger ribonucleic acid (mRNA) vaccine. Moreover, the newly emerged Omicron XBB subvariant remains unneutralized by the catches induced by a booster dose of the bivalent vaccine containing the mRNA sequences of the Omicron BA.5 and ancestral spike (S) proteins.

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 catches in the serum of vaccinees. Thus, there remains an urgent need for a pan-sarbecovirus vaccine capable of neutralizing current and future variants of SARS-CoV-2.

About the study

In the current study, researchers administered three doses of either CF501/RBD-Fc or Alum/RBD-Fc vaccines in two groups, each consisting of three rhesus macaques. Sera were then collected to assess IgG and RBD-binding nAb titers through the use of an enzyme immunoassay (ELISA) and virus neutralization assays.

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

Results

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

Although the final 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 doses of vaccine and remained elevated until day 191 following the first vaccination.

The 50% neutralizing titers (NT50) of bnAbs in CF501/RBD-Fc macaque sera were much higher than those of the Alum/RBD-Fc group against all pseudotyped viruses, with NT50 values of 436 and 313 against BQ .1.1 and XBB at day 28, respectively. Cross-neutralizing bnAb titers in the CF501/RBD-Fc group continued to increase after the third vaccination, with NT50 values at day 122 of 2118 and 2526 against BQ.1.1 and XBB after receiving the first dose of vaccine, respectively.

These titers also increased in the Alum/RBD-Fc group after three doses of vaccine; however, these values have increased slightly compared to BQ.1.1 and XBB. Eventually, NT50 values decreased in both groups. The third vaccine dose did not cause an increase in NT50 titers against D614G, but a drastic increase in bnAb titers against Omicron subvariants.

Although their NT50 against BQ.1.1 and XBB decreased 26.9 and 22.5 times compared to D614G, respectively, these bnAbs effectively neutralized BQ.1.1 and XBB infection. Virus neutralization test results 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.

conclusion

Overall, the study results indicate that CF501 adjuvant stimulated conservative but non-dominant RBD epitopes to generate bnAbs against pan-sarbecovirus vaccines. Thus, researchers recommend replacing the adjuvant in first-generation COVID-19 subunit vaccines with CF501 for next-generation booster vaccinations. This strategy could improve 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 pan-sarbecovirus vaccine based on the RBD of the original strain of SARS-CoV-2 elicits potent neutralizing antibodies against XBB in non-human primates. PNAS. doi:10.1073/pnas.2221713120

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She holds a Masters degree from the University of Rajasthan with a major in Biotechnology in 2008. She has experience in pre-clinical research through 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.