オミクロン株に対してファイザーなどのmRNAワクチンはもうアカンかも・・・

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改良版ワクチンの開発を疎かにして初期型のを使い続けてきたツケが今頃になってドッと出てきたんでしょううね。

 

◆Effectiveness of a third dose of BNT162b2 mRNA COVID-19 vaccine in a large US health system: A retrospective cohort study【The Lancet　2022年2月14日】

Summary

Background

Globally, recommendations are expanding for third (booster) doses of BNT162b2 (Pfizer–BioNTech). In the United States, as of November 19, 2021, boosters were recommended for all adults aged 18 years and older. We evaluated the effectiveness of a third dose of BNT162b2 among adults in a large US integrated health system.

Methods

In this retrospective cohort study, we analyzed electronic health records from Kaiser Permanente Southern California between Dec 14, 2020 and Dec 5, 2021 to assess vaccine effectiveness (VE) of two and three doses of BNT162b2 against SARS-CoV-2 infections (without hospital admission) andCOVID-19-related hospital admission. VE was calculated using hazards ratios from adjusted Cox models.

Findings

After only two doses, VE against infection declined from 85% (95% CI 83–86) during the first month to 49% (46–51) ≥ 7 months following vaccination. Overall VE against hospitalization was 90% (95% CI 86–92) within one month and did not wane, however, effectiveness against hospitalization appeared to wane among immunocompromised individuals but was not statistically significant (93% [72–98] at 1 month to 74% [45–88] after ≥ 7 months; p=0·490). Three-dose VE (median follow-up 1·3 months [SD 0·6]) was 88% (95% CI 86–89) against infection and 97% (95–98) against hospitalization. Effectiveness after three doses was higher than that seen one month after receiving only two doses for both outcomes. Relative VE of three doses compared to two (with at least six months after the second dose) was 75% (95% CI 71−78) against infections and 70% (48−83) against hospital admissions.

Interpretation

These data support the benefit of broad BNT162b2 booster recommendations, as three doses confers comparable, if not better, protection against SARS-CoV-2 infections and hospital admission as was seen soon after receiving two doses.

Funding

Pfizer Inc.

◆Effectiveness of the BNT162b2 vaccine among children 5-11 and 12-17 years in New York after the Emergence of the Omicron Variant【medRxiv　2022年2月25日】

Introduction

In New York State (NYS), nearly 850,000 children ≤17 years have been diagnosed with COVID-19. Randomized trails and observational studies conducted during the Delta and earlier variants’ predominance, indicate the BNT162b2 vaccine, developed to protect against original strains, is safe and effective in preventing COVID-19 outcomes in those 5-17 years and older.1-10 Compared to children 12-17 years, who receive two 30μg doses, less is known known about real-world vaccine effectiveness against infection and hospitalization effectiveness for children 5-11 years, who receive two 10μg doses, particularly after the Omicron variant’s emergence.11,12 We examined the effectiveness of vaccination during the Omicron variant surge that began in early December 2021 on infection and hospitalization among children 5-11 years compared to 12-17 years using NYS statewide surveillance systems.

 

◆Fourth dose of COVID vaccine offers only slight boost against Omicron infection【Nature：Smriti Mallapaty　2022年2月23日】

Israeli trial shows a fourth vaccination raises antibody levels but provides little extra protection against SARS-CoV-2 infection.

A fourth dose of a COVID-19 vaccine restores antibodies to levels observed after the third dose but provides only a modest boost in protection against infection, according to a small trial carried out in Israel1.

The study, posted on the medRxiv preprint server on 15 February without peer review, suggests that current mRNA vaccines hit a “ceiling of immunity” after the third dose, says Miles Davenport, a computational immunologist at the University of New South Wales in Sydney, Australia. Further doses will probably only recover the immunity lost over time owing to waning, he says.

“The third dose is really, really important,” says Gili Regev-Yochay, a physician and infectious-diseases researcher at Sheba Medical Center in Ramat Gan, who co-authored the study. But “people who are young and healthy and don’t have risk factors will probably not benefit much from a fourth dose” when faced with Omicron, she says.

Still, she and others say the fourth dose could be beneficial for people at higher risk of severe illness. Several countries, including Israel, Chile and Sweden, are offering fourth doses to older adults and other groups.

Starting in late 2021, Regev-Yochay and her colleagues enrolled 274 health-care workers in a clinical trial, in which they were given their fourth shot of an mRNA vaccine at least four months after their third. Some received the vaccine made by New York-based Pfizer with BioNTech in Mainz, Germany; others received that made by Moderna, based in Cambridge, Massachusetts.

Regardless of the vaccine brand, the fourth dose raised participants’ levels of ‘neutralizing’ antibodies, which can block viral infection of cells. But levels after the fourth dose did not surpass those observed shortly after the third dose, suggesting that the vaccines had hit an upper limit. “You can’t keep boosting antibody responses forever,” says Davenport.

Omicron challenge

The researchers also assessed the neutralizing antibodies from 25 participants for the antibodies’ power against several SARS-CoV-2 variants. They found that, after the third vaccine dose, participants’ antibodies could block Omicron from infecting cells — but not as well as they blocked the Delta variant. After the fourth dose, the antibodies’ potency against Omicron rose but also not more than their potency against Delta.

Those antibody data might explain why the fourth dose did not translate into substantial extra protection against infection with Omicron. A four-dose course of the Pfizer vaccine was 30% more protective against infection than a three-dose course; for Moderna, that extra efficacy was 11%.

That meant that, by the end of January, 52 participants who had received a fourth dose had tested positive for SARS-CoV-2 and 73 of the matched controls who had received only three doses had done so. Most of the infections were mild, and none of the participants in either the control group or the four-dose group developed severe COVID-19.

The relatively small increase in efficacy between the third and fourth doses is probably because protection offered by three doses is “already quite high”, says Davenport. Both vaccines offered slightly more protection against symptomatic disease than against infection.

Chasing boosters

Ran Balicer, a public-health physician at the Clalit Health Institute in Tel Aviv, notes that the trial’s efficacy estimates are based on a small sample size and have wide margins of uncertainty. Other observational studies2 from Israel have shown higher levels of protection against infection and severe disease. “This additional protection could make a large difference for high-risk groups during a surge,” says Balicer.

Ultimately, the study points to the need for new vaccines that can prevent infection with emerging variants, say researchers. The findings also highlight the importance of clarifying the optimal number of doses and time between doses for existing vaccines, says Gagandeep Kang, a virologist at the Christian Medical College in Vellore, India. “I don’t think chasing an ever-increasing number of doses is going to be the solution for Omicron or future variants.”

 

→Nature – Omicron & antibodies – Volume 602 Issue 7898, 24 February 2022

 

◆Decoding COVID-19 mRNA Vaccine Immunometabolism in Central Nervous System: human brain normal glial and glioma cells by Raman imaging【bioRxiv　2022年3月2日】

Abstract

The paper presents the effect of COVID-19 mRNA (Pfizer/BioNT) vaccine on in vitro glial cells of the brain studied by means of Raman spectroscopy and imaging.. The results obtained for human brain normal and tumor glial cells of astrocytes, astrocytoma, glioblastoma incubated with the Covid-19 mRNA vaccine Pfizer/BioNT vaccine show alterations in the reduction-oxidation pathways associated with Cytochrome c.

We found that the Pfizer/BioNT vaccine down regulate the concentration of cytochrome c in mitochondria upon incubation with normal and tumorous glial cells. Concentration of oxidized form of cytochrome c in brain cells has been shown to decrease upon incubation the mRNA vaccine. Lower concentration of oxidized cytochrome c results in lower effectiveness of oxidative phosphorylation (respiration), reduced apoptosis and lessened ATP production. Alteration of Amide I concentration, which may reflect the decrease of mRNA adenine nucleotide translocator. Moreover, mRNA vaccine leads to alterations in biochemical composition of lipids that suggest the increasing role of signaling. mRNA vaccine produce statistically significant changes in cell nucleus due to histone alterations. The results obtained for mitochondria, lipid droplets, cytoplasm may suggest that COVID-19 mRNA (Pfizer/BioNT) vaccine reprograms immune responses. The observed alterations in biochemical profiles upon incubation with COVID-19 mRNA in the specific organelles of the glial cells are similar to those we observe for brain cancer vs grade of aggressiveness.

 

→Pfizer’s Documents – Public Health and Medical Professionals for Transparency

 

◆Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line【MDPI　2022年2月25日】

Abstract

Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.