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A recent article posted to the Research Square* preprint server analyzed the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing capacity of sera samples from two-dose BNT162b2 vaccinated Japanese subjects.

Background

Following the emergence of SARS-CoV-2 in Wuhan, China, in late 2019, vytorin ultrafarma the coronavirus disease 2019 (COVID-19) pandemic has spread internationally at an unprecedented rate. To date, SARS-CoV-2 has caused more than 485 million cases and 6.1 million deaths across the globe.

Since the beginning of the SARS-CoV-2 pandemic, pharmaceutical companies and scientists worldwide have been working hard to produce vaccines effective against COVID-19.

There are over 30 clinically approved SARS-CoV-2 vaccines so far, and they have minimized the COVID-19-related deaths greatly. However, the subsequently emerged SARS-CoV-2 Delta, Beta, Gamma, and Alpha variants of concern (VOCs) and the Kappa variant under monitoring (VUM), have enhanced the viral fitness and immune evasion capacities against COVID-19 or its vaccination-induced immune responses.

About the study

In the current prospective work, the researchers monitored 225 medical personnel vaccinated with two doses of BNT162b2 COVID-19 vaccine with a three-week gap from Kumamoto General Hospital, Japan, for more than 150 days. The 50% neutralizing activity (NT50) of sera samples against 10 SARS-CoV-2 isolates, including the wildtype (WT) strain and nine different variants (consisting of Delta, Gamma, Beta, and Alpha VOCs, and Kappa VUM), were analyzed 60 days following the initial dose. This evaluation was done in 211 sera samples against the WT strain and 45 samples against the other nine SARS-CoV-2 variants using Vero E6 transmembrane serine protease 2 (TMPRSS2) cells.

Instead of pseudo or recombinant SARS-CoV-2 viruses, the SARS-CoV-2 strain and variants employed in this work were infectious viruses isolated from patients at hospitals or airport quarantine stations in Japan. 

Antiviral activity or half-maximal effective concentration (EC50) of immunoglobulin G (IgG) in 45 sera samples against the 10 SARS-CoV-2 isolates was assessed 60 days-post first dose BNT162b2 vaccination. The antiviral activity was estimated in sera samples from people categorized as high (IgG^high) or moderate (IgG^moderate) responders according to their neutralizing activity against each SARS-Cov-2 variant versus the WT strain. The IgG concentrations of the sera samples from 25 subjects at 28-day, 90-day, and 150-day timeframes were estimated. Subsequently, the time-dependent changes of IgG activity in these sera samples against the 10 SARS-CoV-2 isolates were evaluated.

Results and discussions

The results indicated that the SARS-CoV-2 Beta variant comprising D614G, N501Y, E484K, and K417N mutations in the spike (S) expressing region had the highest reductions in susceptibility profile towards COVID-19 vaccinations. The reductions in average NT50 of the Beta VOC were 83.4% and 88.5% for moderate and high responders, respectively, relative to the SARS-CoV-2 WT isolate. 

The absolute EC50 estimates of IgG^highs against the WT isolate and VOCs and VUM were 1.9 to 3.2-times lower than the EC50 estimates of IgG^moderates. According to the authors, this difference was either due to better quality of IgG in high responders or a significant abundance of SARS-CoV-2 S-specific IgGs in high responders than moderate responders. The neutralizing activity of sera from high responders at 28, 60, 90, and 150 days following the first COVID-19 vaccine dose was superior and only waned slowly relative to moderate responders. 

The time order of the emergence of SARS-CoV-2 variants was the WT strain, Beta VOC, Alpha VOC, Delta VOC, Kappa VOC, and Gamma VOC. Nevertheless, the vulnerability of the 10 evaluated SARS-CoV-2 isolates towards vaccine-induced neutralizing activity did not reduce according to the temporal sequence of their emergence. These findings show that the SARS-CoV-2 variants did not arise in chronological order based on evolutionary characteristics. In addition, they also suggest that SARS-CoV-2 variants emerge via local evolution and transmission, and a co-expansion propensity of each virus throughout nearby nations and areas with varied origins and transmission channels exists.

The SARS-CoV-2 Kappa and Delta variants that originated from India displayed a distinct time-dependent reduction in antiviral characteristics of IgG induced by the BNT162b2 vaccination. Kappa had a moderate to robust immune evasion phenotype, likely attributable to the E484Q mutation in its S-encoding region, while the Delta variant has no mutation in this amino acid. The IgG from two-dose BNT162b2 vaccinated Japanese people exhibited comparatively long-standing, i.e., nearly 150 days following the initial dose, neutralizing activity against the Delta VOC.

Conclusions

The study findings depicted that the NT50 of Day-60 sera against the SARS-CoV-2 Beta VOC demonstrated the highest drop compared to other SARS-CoV-2 isolates assessed. The IgG of moderate responders (IgG^moderates) and high responders (IgG^highs) displayed equal fold of EC50 changes against all SARS-CoV-2 variants relative to the WT strain. Nevertheless, absolute EC50 of IgG^moderates was two to three times greater than the IgG^highs EC50 against all SARS-CoV-2 variants.

The EC50 of IgG measured at several time intervals from 28 days to 150 days timestamps demonstrated a time-dependent decrease in IgG activity against various SARS-CoV-2 VOCs and Kappa VUM. Yet, both IgG had significantly long-standing beneficial EC50 at least at the 150 days timestamp against the Delta VOC.

Altogether, the present work strongly implies that the quick expansion of vaccine delivery in Japan was extraordinarily efficient in containing the SARS-CoV-2 pandemic via the spread of the Delta VOC. This study also provides deep insights into the antiviral effectiveness of the COVID-19 vaccine and vaccine-induced host immune responses.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.