Pfizer and BioNTech Announce BNT162b2 Vaccine Maintains Neutralizing Activity Against Key SARS-CoV-2 Variants

Today, Pfizer and BioNTech jointly announced that an in vitro study demonstrated that sera from individuals vaccinated with the BNT162b2 COVID-19 vaccine retain neutralizing activity against key mutations present in several recently emerging SARS-CoV-2 variants. This study, conducted collaboratively by researchers from Pfizer and the University of Texas Medical Branch, was published in Nature Medicine, a subsidiary journal of Nature.

Recently, mutant strains of SARS-CoV-2 have been successively identified in the United Kingdom (B.1.1.7), South Africa (B.1.351), and Brazil (P1). Genetic mutations of concern to scientists include N501Y, E484K, D614G, and the deletion mutation at positions 69/70 (ΔH69/ΔV70) in the spike (S) protein. Among these, the N501Y, E484K, and D614G mutations are all located within the receptor-binding domain (RBD) of the spike protein. The RBD is the key site for binding to the ACE2 receptor on the surface of human cells and serves as an important antigen recognized by various neutralizing antibodies. Therefore, mutations occurring in the RBD may not only enhance the affinity of the spike protein for the receptor, thereby increasing the transmissibility of SARS-CoV-2, but also enable the virus to evade recognition by certain neutralizing antibodies.

A recent study published in Nature indicates that the ΔH69/ΔV70 variant emerged in a patient with chronic SARS-CoV-2 infection. This mutation, located in the N-terminal domain of the spike protein, may induce conformational changes in the spike protein.

▲ Key genetic mutations in the SARS-CoV-2 spike protein that have drawn scientists’ attention (Image source: Reference [1])

To investigate whether the BNT162b2 COVID-19 vaccine confers protective efficacy against SARS-CoV-2 variants carrying these genetic mutations, researchers obtained serum samples from 20 volunteers enrolled in a clinical trial. These participants provided serum samples either 2 or 4 weeks after receiving two doses of the BNT162b2 vaccine.

Subsequently, researchers engineered SARS-CoV-2 mutant strains with various combinations of genetic mutations based on the wild-type virus using genetic engineering techniques, and evaluated the neutralizing efficacy of serum samples obtained from 20 volunteers against these different SARS-CoV-2 mutant strains.

The experimental results showed that, against the mutant strain containing Δ69/Δ70+N501Y+D614G, the neutralizing antibody titers in 10 out of 20 serum samples increased two-fold compared to the wild type, indicating an enhanced neutralization capacity (Figure b below).

For the mutant strain carrying E484K+N501Y+D614G, the neutralizing antibody titers were reduced by half in 6 out of 20 serum samples compared to the wild type, indicating a decline in neutralizing capacity (Figure c below).

▲ Changes in neutralizing antibody titers of immune sera against different SARS-CoV-2 mutant strains (Image source: Reference [1])

Overall, compared with the wild-type strain, only the geometric mean titer (GMT) of neutralizing antibodies against the E484K+N501Y+D614G mutant strain showed a decrease. However, the decline in GMT was not substantial, with a ratio of 0.81 relative to the wild-type GMT. The researchers pointed out in their paper that for influenza vaccines, a four-fold decrease in neutralizing antibody titers is an indicator that may necessitate vaccine updates. The currently observed change in neutralizing antibody titers remains small compared to this threshold.

▲ Geometric mean titers (GMTs) of neutralizing antibodies against mutant strains and their ratios to GMTs against the wild-type strain (Image source: Reference [1])

The researchers also pointed out that one of the limitations of this study is that the genetically engineered mutant SARS-CoV-2 strains did not include all the genetic mutations carried on the spike protein of the B.1.1.7 or B.1.351 variants, so the potential impact of complex interactions among these genetic mutations cannot yet be assessed.

Currently, SARS-CoV-2 genetic mutations such as N501Y and E484K have emerged independently in multiple countries and regions worldwide, suggesting that these variants may confer a competitive advantage to the virus. Researchers state that the continuous evolution of SARS-CoV-2 necessitates ongoing monitoring of changes in vaccine efficacy. Furthermore, this surveillance must be conducted in conjunction with efforts to update vaccines, thereby preparing for potential future mutations.

Note: This article is intended to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a licensed healthcare provider at an accredited hospital.

References:

[1] Xie et al., (2021). Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nature Medicine, https://doi.org/10.1038/s41591-021-01270-4.

[2] Pfizer and BioNTech Publish Data from In Vitro Studies in Nature Medicine Demonstrating COVID-19 Vaccine Elicits Antibodies that Neutralize SARS-CoV-2 with Key Mutations Present in U.K. and South African Variants. Retrieved February 8, 2021, from https://investors.biontech.de/news-releases/news-release-details/pfizer-and-biontech-publish-data-vitro-studies-nature-medicine

▽Follow [WuXi AppTecDe】WeChat Official Account