Alarming Antibody Evasion Properties of Rising SARS-CoV-2 Variants Raise Concerns for Vaccine Efficacy

BQ and XBB subvariants show marked impairment in neutralization by sera from vaccine recipients and infected individuals, including those boosted with mRNA vaccines

A new study has revealed alarming antibody evasion properties of two rapidly spreading subvariants of the SARS-CoV-2 Omicron variant, called BQ and XBB. These subvariants have gained dominance in certain regions of the world and have additional spike mutations that may alter their ability to evade antibodies.

Governments and public health authorities must closely monitor and address spread of BQ and XBB subvariants

The study found that neutralization of the BQ and XBB subvariants by sera from vaccine recipients and infected individuals was markedly impaired, including those who had been boosted with a WA1/BA.5 bivalent mRNA vaccine. The neutralizing titers of these subvariants were found to be 13-81-fold and 66-155-fold lower, respectively, compared to the ancestral strain D614G. This is far beyond what has been observed previously for other variants.

New SARS-CoV-2 subvariants pose serious threat to current vaccines

A panel of monoclonal antibodies, including those with Emergency Use Authorization, was also found to largely inactive against these new subvariants. The spike mutations that conferred antibody resistance were individually studied and structurally explained in the study.

Notably, the spike proteins of these subvariants were found to have similar ACE2-binding affinities as their predecessors, suggesting that their observed growth advantage may be due to their extreme antibody evasion properties. This raises serious concerns about the efficacy of current COVID-19 vaccines against these subvariants and the possibility of a surge in breakthrough infections and re-infections.

Monoclonal antibodies authorized for COVID-19 treatment and prevention ineffective against new subvariants

The study also highlighted the urgent need to develop active monoclonal antibodies for clinical use, as the current authorized monoclonal antibody, bebtelovimab, was found to be completely ineffective against these subvariants. This poses a particular problem for immunocompromised individuals who may not respond robustly to vaccines.

These findings indicate that the BQ and XBB subvariants present a significant threat to the global effort to control the COVID-19 pandemic. It is crucial for governments and public health authorities to closely monitor the spread of these subvariants and consider implementing measures to mitigate their impact. This may include the development and distribution of new vaccines and treatments that are effective against these subvariants, as well as continuing to prioritize vaccination efforts and implementing measures to reduce transmission.

What is the concern with the new SARS-CoV-2 BQ and XBB subvariants?

These subvariants have been found to possess alarming antibody evasion properties, meaning they may be able to evade the immune responses of vaccinated individuals or those who have previously been infected with the virus. This could compromise the efficacy of current COVID-19 vaccines and result in a surge of breakthrough infections and re-infections.

How do these subvariants evade antibodies?

These subvariants have evolved additional mutations in their spike proteins, the proteins the virus uses to enter human cells. These mutations appear to “fill up the holes” that allow specific monoclonal antibodies to neutralize the virus, making the subvariants resistant primarily to neutralization by these antibodies.

Crowds gather in Berlin to speak out against the government’s handling of the pandemic, 2021 (PICTURE: MICHAEL KUENNE / PRESSCOV)
Is this a high alarm situation?

The rapid emergence and spread of these subvariants and their extreme antibody evasion properties make this a cause for concern. It is important for governments and public health authorities to closely monitor the spread of these subvariants and consider implementing measures to mitigate their impact.

How can we prevent the spread of these subvariants?

Measures such as vaccines, masks, physical distancing, and hand hygiene can help reduce the spread of these subvariants, as well as any other variant of the virus. It is important for individuals to continue following recommended public health guidelines and for governments to prioritize vaccination efforts.

How effective are current COVID-19 vaccines against these subvariants?

According to the study, neutralization of the BQ and XBB subvariants by sera from vaccinees was markedly impaired, including sera from individuals who had received a bivalent mRNA vaccine. However, it is worth noting that this is a preprint that has not yet undergone peer review, so the findings should be interpreted with caution. It is important for ongoing research to continue to assess the effectiveness of current vaccines against these subvariants.

What should governments do about these subvariants?

Governments should closely monitor the spread of these subvariants and consider implementing measures to mitigate their impact. This may include developing and distributing new vaccines and effective treatments against these subvariants, as well as continuing to prioritize vaccination efforts and implementing measures to reduce transmission.