The Pfizer-BioNTech vaccine shows promise against new SARS-CoV-2 modifications

The chronic pandemic of coronavirus disease 2019 (COVID-19), caused by the severe pathogen respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in more than 103 million infections over 2.2 million deaths across the world. As effective antivirals and safe antivirals have not yet been identified, the focus has largely been on non-pharmacological interventions (NPIs). These have included a tremendous amount of attention to hand washing, wearing masks in public, social distance and locksmiths at various levels (regional or national).

In addition, the rise of new strains of SARS-CoV-2 that have shown higher release potential has led to questions about the neutral efficacy of the permitted vaccines currently being administered in many parts of the country. the world. Against this background, a team of US-based researchers at the University of Texas Medical Branch and Pfizer studied the Pfizer-BioNTech vaccine candidate – currently being rolled out in many parts of the world to high-risk humans – to see if it still exists up against mutant strains of the virus. In doing so, the team achieved encouraging results.

The importance of vaccines against COVID-19

The only hope for long-term control of this pandemic appears to be through the use of world-class vaccines. As a result, considerable scientific effort has been expended on the development of safe and effective COVID-19 vaccines. These have been based on several platforms, including DNA and RNA, attenuated live virus, inactivated virus, and viral proteins.

While some vaccines such as the Pfizer-BioNTech, Moderna and Oxford-Astra-Zeneca vaccines are available recently, with millions having received one or more doses in different countries, there are many more at later stages of clinical development. These include BNT162b2 (i.e., the Pfizer-BioNTech vaccine), a nucleoside-modified RNA-based vaccine.

This RNA vaccine model incorporates the encoding of viral genetic material for the full-time viral spike protein in its stable prefusion form.

Earlier results

The BNT162b2 model has been shown to induce neutral antibodies to the virus in a dose-dependent manner. The average geometric titers (GMTs) were either equal to or higher than those measured in a series of human serum samples from COVID-19 convalescent patients.

The same researchers tested a placebo-controlled trial of the BNT162b2 vaccine, involving approximately 44,000 participants aged 16 years or older. Two doses of the vaccine were given. The vaccine was found to be 95% or more effective against the disease.

However, in the current study by the same team of scientists, the focus is on whether the BNT162b2 vaccine is effective in preventing disease caused by emerging SARS-CoV-2 mutations. new and rapidly spreading, encompassing the UK, South Africa, and other regions of the world.

The reason for such questions is that the new variants have several mutations in their spike proteins, which are the targets of most known neutralizing antibodies. Therefore, the researchers aimed to test the effect of the most important spike mutations on the neutral antibodies received by this vaccine.

Study details

The researchers first created three spike mutant viruses based on USA-WA1 / 2020 clinical weight. The first is a N501Y spike mutation found on both different UK and South African variants. Mutation affects the viral receptor-binding domain (RBD).

The mutant form of the spike not only strengthens the virus’s binding to the host cell receptor angiotensin-converting enzyme 2 (ACE2), making the variant more infectious, but also allows the virus to catch mice .

The second mutant contains a set of mutations, delete 69/70, N501Y, and D614G. Of these, the first is on the N-terminal domain of the S1 subsurface of the spike, and it has been suggested that it alters allosteric alteration in the S1 subunit conformation. The D614G mutation is present in most circulating series worldwide.

The third mutant contains E484K mutants, as well as N501Y and D614G mutants. Mutation of E484K can also be found on the RBD, and will affect the differentiation in which many monoclonal antibodies occur.

When compared to the USA-WA1 / 2020 wildtype strain, the researchers found that all three produced similar records in cell culture. They tested sera from 20 participants who had received two doses of the vaccine, at 21-day intervals. The serum was taken either 2 or 4 weeks after the second dose.

All serum samples were tested for their ability to neutralize the wildtype strain and the three mutant strains, using the 50% plaque reduction neutralization assay (PRNT50). The neutralization titers were relatively comparable for all sera, whether for the mutant or wild-type viruses, with a difference of less than four times that between the highest and lowest neutralization titers.

Results and effects

Of the 20 sera, ten with dual titers neutralized against the Δ69 / 70 + N501Y + D614G virus compared to the wildtype virus, but six showed neutral activity against the E484K + N501Y + D614G virus only. with only half of the titers displayed against the wildtype virus.

The neutral GMTs of serum against the N501Y were ~ 1.5 times the GMTs against the wildtype virus, while the Δ69 / 70 + N501Y + D614G and E484K + N501Y + D614G viruses were GMTs of neutral antibodies that were 1.4 and 0.8 the GMTs against the wildtype virus, respectively. These differences are too small to indicate any change in vaccine efficacy.

With flu vaccines, a fourfold difference in hemagglutinin-inhibitory titer titers indicates a significant change in influenza sex. Using the same criteria, these mutations do not appear to affect the ability of antibodies ingested with two doses of BNT162b2 to neutralize the mutants studied here, in comparison. to parental pressure.

The viruses used in this study do not cover all mutations in the UK or mutations in South Africa, but this may not affect the results of the neutralization assessments. Second, the study does not include data on the correlation of media protection against COVID-19.

For this reason, the neutralization titers are used to predict vaccine efficacy. These predictions are based on assumptions about the titers of neutralizing antibodies required for effective neutralization and how antibodies enhance protection with COVID-19 vaccines compared to mid-cell immunity.

As a result, clinical data are essential to gain a solid understanding of the efficacy of the vaccine against these new variables. At the same time, the global disease situation should be monitored without interruption in order to avoid dangerous stress, and to introduce necessary changes in the available vaccines. Such changes in the routine mRNA vaccine are easy, due to the flexible platform used.

* Important message

bioRxiv publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be seen as final, guiding health-related clinical practice / behavior, or be treated as information established.