2021年6月17日木曜日
Research suggests Pfizer-BioNTech COVID-19 vaccine reprograms innate immune responses
Researchers in The Netherlands and Germany have warned that Pfizer-BioNTech’s coronavirus disease 2019 (COVID-19) vaccine induces complex reprogramming of innate immune responses that should be considered in the development and use of mRNA-based vaccines.
Jorge Domínguez-Andrés and colleagues say that while the vaccine has been shown to be up to 95% effective in preventing infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent COVID-19, little is known about the broad effects the vaccine may have on the innate and adaptive immune responses.
In the current study (not peer-reviewed*), the research team from Radboud University Medical Center and Erasmus MC in the Netherlands, and the Helmholtz-Centre for Infection Research (HZI), Hannover Medical School (MHH), and the University of Bonn, in Germany, confirmed the efficacy of BNT162b2 vaccination at inducing effective humoral and cellular immunity against several SARS-CoV-2 variants.
However, they also showed that the vaccine altered the production of inflammatory cytokines by innate immune cells following stimulation with both specific (SARS-CoV-2) and non-specific (viral, fungal and bacterial) stimuli.
Following vaccination, innate immune cells had a reduced response to toll-like receptor 4 (TLR4), TLR7 and TLR8 – all ligands that play an important role in the immune response to viral infection.
Neta and colleagues also found that cytokine responses to fungi were increased following vaccination.
The mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses, which should be considered in the development and use of this new class of vaccines,” writes the team.
A pre-print version of the research paper is available on the medRxiv* server. A preprint is a version of a scholarly or scientific paper that precedes formal peer review and publication in a peer-reviewed scholarly or scientific journal.
The accelerated development of new vaccine technologies
Since the COVID-19 pandemic began in late December 2019, researchers across the globe have been racing to develop vaccines to help combat the global healthcare crisis.
The scale of the pandemic has led to the accelerated development of new mRNA-based vaccines, the first of which to be registered was the BNT162b2 vaccine from Pfizer-BioNTech.
This vaccine is based on a lipid nanoparticle–formulated, nucleoside-modified mRNA that encodes the spike protein of the SARS-CoV-2 strain that was isolated early on in the pandemic in Wuhan, China.
The spike protein is the main structure the virus uses to infect host cells, and its receptor-binding domain (RBD) is a primary target of neutralizing antibodies following natural infection or vaccination.
Several phase 3 trials have shown that BNT162b2 elicits broad humoral (antibody) and cellular responses that protect against COVID-19. However, many challenges remain while this and other mRNA-based vaccines are rolled out globally, with the emergence of new variants being of particular concern.
The variants that have emerged in the UK (B.1.1.7 lineage), South Africa (B.1.351), and Brazil (P.1) contain multiple mutations in the spike that could impact disease severity, viral transmissibility, and vaccine effectiveness.
The capacity of BNT162b2 to induce effective humoral and cellular immunity against the new SARS-CoV-2 variants is only now beginning to be understood,” says Domínguez-Andrés and colleagues.
Furthermore, an unexplored area is whether BNT162b2 vaccination has long-term effects on innate immune responses:
This could be very relevant in COVID-19, in which dysregulated inflammation plays an important role in the pathogenesis and severity of the disease,” writes the team. “Multiple studies have shown that long-term innate immune responses can be either increased (trained immunity) or down-regulated (innate immune tolerance) after certain vaccines or infections.”
What did the researchers do?
The researchers showed that one dose of the BNT162b2 vaccine induces high concentrations of anti-spike and anti-spike RBD antibodies, while a second dose three weeks later elicits even higher levels.
All the post-vaccine serum samples tested effectively neutralized the B.1.1.7 variant, but 37.5% showed decreased neutralizing activity against the B.1.351 variant.
These data support the evidence that B.1.351, and possibly other variants, may be able to escape vaccine-induced humoral immunity to a certain extent,” say the researchers.
What about the cellular response?
Vaccination with BNT162b2 has been reported to activate SARS-CoV-2-specific CD4+ and CD8+ T cells, and to increase the production of immune-modulatory cytokines such as interferon-γ (IFN-γ).
Domínguez-Andrés and colleagues, therefore, assessed the secretion of IFN-γ from peripheral blood mononuclear cells (PBMCs) in response to different SARS-CoV-2 strains before and after BNT162b2 vaccination.
TNF-α and IFN-α production in response to heterologous stimuli in PBMCs isolated from vaccinated subjects. (A) Description of the study: vaccination and blood collection days. (B-G) Fold change values of TNF-α production are calculated individually for each subject by division of t2:t1 and t3:t1. Data are presented as fold changes ± SEM (n=15-16) and analysed by Wilcoxon’s matched-pairs signed-rank test comparing each ratio to t1=1 (red line). (H-I) IFN-α production (pg/ml) at t1, t2 and t3. Data are presented as cytokine concentration ± SEM (n=15-16) and analysed by Wilcoxon’s matched-pairs signed-rank test.
Vaccination increased IFN-γ production by at least 50% in 37.5% of the samples stimulated with the standard SARS-CoV-2 strain, in 50% stimulated with the B.1.1.7 or B.1.351 variant, but only in 18.8% of samples stimulated with the Bavarian variant.
These findings argue that BNT162b2 vaccination induces better humoral than cellular immune responses,” say the researchers.
Cytokine responses to certain stimuli were reduced following vaccination
Interestingly, BNT162b2 vaccination decreased IFN-γ production following stimulation with the TLR7 and TLR8 agonist R848. The TLR7 and TLR8 ligands are key players in the immune response to viral infection.
Vaccination also decreased production of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β following stimulation with either the standard SARS-CoV-2 strain or different Toll-like receptor ligands.
In contrast, responses to the fungal pathogen Candida albicans were higher after vaccination.
In addition, the production of the anti-inflammatory cytokine interleukin-1Ra was reduced in response to Toll-like receptor 4 and C. albicans. This also suggests a shift towards increased inflammatory responses to fungi following vaccination, say the researchers.
These results collectively demonstrate that the effects of the BNT162b2 vaccine go beyond the adaptive immune system,” writes the team. “The BNT162b2 vaccine induces reprogramming of innate immune responses as well, and this needs to be taken into account.”
What do the authors advise?
The researchers say that in combination with strong adaptive immune responses, the reprogramming of innate responses could either contribute to a more balanced inflammatory reaction to SARS-CoV-2 infection or a weakened innate immune response.
The effect of the BNT162b2 vaccination on innate immune responses could also interfere with the responses to other vaccinations, adds the team.
Our findings need to be confirmed by conducting larger cohort-studies with populations with diverse backgrounds, while further studies should examine the potential interactions between BNT162b2 and other vaccines,” concludes Domínguez-Andrés and colleagues.
* Important Notice
medRxiv 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.
Journal reference:
- Domínguez-Andrés J, et al. The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses. medRxiv, 2021. doi: https://doi.org/10.1101/2021.05.03.21256520, https://www.medrxiv.org/content/10.1101/2021.05.03.21256520v1
https://www.news-medical.net/news/20210510/Research-suggests-Pfizer-BioNTech-COVID-19-vaccine-reprograms-innate-immune-responses.aspx
人間の免疫システムなんぞ長年の進化の過程で個人によってそれぞれ微妙に異なるわけで、それを安易にいじくって無事に済むと思ってるとか、現代医学・薬学・科学に携わる者どもの傲慢と無知と愚かさ以外の何物でもない。
2021年6月18日金曜日
自然免疫システムが弱体化したら不衛生な後進国では生きていけなくなる
対症療法（たいしょうりょうほう、英: symptomatic therapy）とは、疾病の原因に対してではなく、主要な症状を軽減するための治療を行い、自然治癒能力を高め、かつ治癒を促進する療法である[1]。姑息的療法とも呼ばれる[2]。
転じて医学以外の分野においても、比喩として、「根本的な対策とは離れて、表面に表れた状況に対応して物事を処理すること[2]」という意味で用いられることがある。なお「対処療法」という表記は誤りである。
対症療法に対して、症状の原因そのものを制御する治療法を原因療法という。病気そのものを治療するには、原因療法や自然治癒力の助けが必要である。また、疾患の多くは直接の原因と複数の遠因が重なりあって起こるため、原因療法と対症療法の区別は相対的なものである。
原因療法（げんいんりょうほう）は、症状や疾患の原因を取り除く治療法で、対症療法と対置される。最終的に症状を取り除くには、対症療法や自然治癒力の助けが必要である。また、疾患の多くは直接の原因と複数の遠因が重なりあって起こるため、原因療法と対症療法の区別は相対的なものである。
要するに安易にｍRNAワクチンなんぞで自然免疫システムをいじくるとその後はあらゆる病気やケガが治癒しなくなるリスクがかなり高い確率で発生するわけですよ。何故かというと自然界に存在しない人工的ｍＲＮＡなんてもんはたとえ短期で消滅しても自然免疫システムにとってはバグとして残るからです。いったんバグが入ってしまったシステムにその後、エラーが生じないわけがない。（爆ｗｗｗｗｗｗｗｗｗ
5 件のコメント:
ワクチンを接種してそういう現象が大規模に起きて、｢因果関係不明｣で納得する奴いるの？
団長おっしゃるとおりですけど
狂った免疫が敵味方かまわず攻撃する自己免疫疾患もお忘れなく
あと、「現代医学ではどうしようもなくなる」は
正しくはどんな医学でも手の打ちようがなくなる可能性がありますし、
現代医学ってむしろそもそも・・・みたいなｗ
至極当然のお話ですよね。
>人間の免疫システムなんぞ長年の進化の過程で個人によってそれぞれ微妙に異なるわけで、
>それを安易にいじくって無事に済むと思ってるとか、現代医学・薬学・科学に携わる者どもの
>傲慢と無知と愚かさ以外の何物でもない。
もともと（自分は頭がいいという）傲慢と、（自分の専門分野以外は）無知、
という連中の集まりだから、性質が悪い。
社会に興味のないチン〇ミサイル軍団、みたいな。
元来、占い師呪術師祈祷師的だった医の道を
誰が、医学と崇め奉るように方向操作したか、でつねwwwwww
本当に団長のおしゃる通りで。。。
今まで神と崇めていた医学が、実は免疫破壊しかしていなくって
私たちを守ってくれて正義の味方だと思ってた政府は国民を、、
今までの価値観全部ひっくり返りそうですよねｗ
民衆に対しての目覚めとしてわざとやってる感ありますよね。
分かるようにゆっくり教えてくれている・・・
厳しさとシニカルさ、そして優しさも感じます。
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