大拡散希望！日本看護倫理学会から大変重要な声明が発表されました。
The Japan Nursing Ethics Association announced the urgent statement!
Please disseminate widely!
[Urgent statement].
Concerns about the Replicon vaccine being introduced to immunize against new coronavirus infections for you and those around you.
Summary
The Japan Nursing Ethics Association expresses its concerns about the safety and ethics of a next-generation mRNA vaccine, a self-amplified mRNA vaccine (Replicon Vaccine), which is the only one in the world approved only in Japan and is scheduled to begin routine vaccination on October 1, 2024.
Introduction.
The mRNA vaccine, a genetically engineered vaccine, was introduced as a means of protection against novel coronavirus infection, and many citizens were vaccinated.
While conventional vaccines induce an immune response in humans by inoculating them with attenuated viruses, bacteria, or other pathogens or their components as antigens, genetically engineered vaccines differ significantly in that the antigens (spike proteins) are produced using the genetic mechanism within human cells.
Then, on November 28 last year, a self-amplified mRNA vaccine (Replicon vaccine) was approved in Japan ahead of the rest of the world (CSL, 2023; Sheridan, 2024), and since then Japan has been the only country in the world to approve it. The approved Replicon vaccine was developed by Arcturus Therapeutics of the U.S., and after large-scale clinical trials (Phase I-III) in Vietnam (Ho" et al., 2024), the vaccine will be manufactured and marketed by Meiji Seika Pharma of Japan.
Replicon vaccines have the ability to replicate themselves in addition to the antigen-producing function of conventional mRNA vaccines, thus producing spike proteins for a long period of time with a small dose of inoculation. The Replicon vaccine is scheduled to be routinely available by October 1, 2024 (Yomiuri Shimbun, 2024), but the Society expresses its concerns about the safety and ethics of this vaccine as follows
1. The problem of Replicon vaccines not being approved in the countries where they were developed and in the countries where they were previously studied.
Eight months have passed since Japan approved the Replicon vaccine, but why has the vaccine still not been approved in the United States, where it was developed, and in other countries around the world, including Vietnam, where a large-scale clinical trial was conducted? This situation reminds us of the drug-arrest incident in Japan, in which a drug that had been withdrawn from the market overseas continued to be used in Japan, resulting in a number of health problems. The fact that the drug is unapproved in other countries makes one suspect that there may be some safety concerns.
2. Shedding problems
There is concern that because replicon vaccines are "self-replicating mRNAs," the replicon vaccine itself may be transmitted (shedding) from the inoculated person to the non-inoculated person (Seneff & Nigh, 2021). In other words, it raises the ethical issue of vaccine components being taken up by unwanted individuals. This is a serious violation of the most important and fundamental ethical principle in medicine: do no harm. Replicon vaccines are designed to be non-infectious (Ricardo-Lax et al., 2021), and this must be demonstrated through clinical research. However, to date, there have been no clinical studies on shedding in such replicon vaccines (Kishida, 2024; MHLW, 2024). In addition to the ethical problem that the Replicon vaccine may cause vaccine components to be taken up by unwanted people, we believe that the routine vaccination from October should not be turned into a demonstration study to confirm whether shedding occurs or not.
3. Future safety issues
Since genetically engineered mRNA vaccines are a technology that utilizes the genetic mechanism within human cells to produce antigenic proteins, their effects on human genetic information and genetic mechanisms, especially on future generations, are of particular concern.
There is strong concern about the persistent claim that mRNA-based vaccines do not alter human DNA, although studies supporting this claim are lacking and are clearly assumptions of uncertain origin (Domazet-Lošo, 2022). Recent studies have reported that sequences from the Pfizer Biontec mRNA vaccine have been reverse transcribed into the DNA of human hepatocytes (Aldén et al., 2022), so the discourse that it does not affect human genetic information is losing ground. As long as these issues remain unresolved, the widespread and continuous use of mRNA vaccines through routine vaccination is problematic.
4. Informed Consent Issues
It has been shown that the serious side effects noted with conventional mRNA vaccines have not been adequately explained to vaccine recipients, both during clinical trials (Cardozo & Veazey, 2021) and after vaccination has actually begun (Slawotsky, 2023), We are very concerned about this situation, which may shake the ideal of medical care based on informed consent. In addition to myocarditis (Hviid et al., 2024) and anaphylaxis (Barta et al., 2024), which have been pointed out with conventional mRNA vaccines, it is important to fully explain the risks of adverse events known at the time of vaccination, such as the possibility of shedding as described above, to the vaccinated persons and ensure their understanding. It is important to fully explain the risks of adverse events that are known at the time of vaccination, such as the possibility of shedding mentioned above. It is then necessary to go through the basic informed consent process in which the vaccinated person himself/herself voluntarily gives his/her consent.
5. Vaccination recommendations and peer pressure issues
In light of the case of conventional mRNA vaccination, it is not difficult to imagine that once the Replicon vaccine becomes a routine vaccination, public opinion and the policies of medical institutions will dictate that health care workers should take the initiative in vaccination. In the name of preventing healthcare workers from becoming a route of infection in order to protect patients, their right to independent self-determination must not be threatened. We also believe that they should never be forced into a situation where they have to be vaccinated with the Replicon vaccine, with the potential to affect not only themselves but also the family members and others around them who have not been vaccinated.
Conclusion.
The Japan Society of Nursing Ethics believes that further research and the collection of long-term safety data are necessary for the introduction of the Replicon vaccine, and that sufficient informed consent must be ensured and that recommendations and peer pressure for vaccination must be eliminated. While we strongly support the development and dissemination of safe and ethically appropriate vaccines, we express our serious concerns about the hasty introduction of replicon vaccines at this stage, when neither of these issues have been addressed.
August 7, 2024
The Japan Nursing Ethiscs Association
Jukai Maeda,
Chairman of the Board
Aldén, M., Olofsson Falla, F., Yang, D., Barghouth, M., Luan, C., Rasmussen, M., & De Marinis, Y. (2022). Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cells.
line. current issues in molecular biology, 44(3), 1115-1126. https://doi.org/10.3390/cimb44030073
Barta, B. A., Radovits, T., Dobos, A. B., Kozma, G. T., Mészáros, T., Berényi, P., ... & Szebeni, J. (2024). Comirnaty- induced cardiopulmonary distress and other symptoms of complement-mediated pseudo-anaphylaxis in a hyperimmune pig model: Causal role of Vaccine: X, 19, 100497. https://doi.org/10.1016/j.jvacx.2024.100497
Cardozo, T., & Veazey, R. (2021). Informed consent disclosure to vaccine trial subjects at risk of COVID-19 vaccines worsening clinical disease. international journal of clinical practice practice, 75(3), e13795. https://doi.org/10.1111/ijcp.13795
CSL.(2023). Japan's Ministry of Health, Labour and Welfare Approves CSL and Arcturus Therapeutics' ARCT-154, the first Self-Amplifying mRNA vaccine approved for COVID in adults. CSL News Releases. https://newsroom.csl.com/2023-11-28-Japans-Ministry-of-Health,-Labour-and-Welfare-Approves-CSL-and- Arcturus- Therapeutics-ARCT-154,-the-first-Self-Amplifying-mRNA-vaccine-approved-for-COVID-in-adults
Domazet-Lošo T. (2022). mRNA Vaccines: Why Is the Biology of Retroposition Ignored? Genes. 13(5),719. https://doi.org/10.3390/genes13050719
Hviid, A., Nieminen, T. A., Pihlström, N., Gunnes, N., Dahl, J., Karlstad, Ø., ... & Hovi, P. (2024). Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort
study. European Heart Journal, 45(15), 1327-1335. https://doi.org/10.1093/eurheartj/ehae056
Ho", N. T., Hughes, S. G.,
Ta, V. T., Phan, L. T., Đo$, Q., Nguye$n, T. V., ... & Nguyen,
X. H. (2024). Safety, immunogenicity and efficacy of the self-amplifying mRNA
ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled
trials. Nature Communications, 15(1), 4081. https://doi.org/10.1038/s41467-024-47905-1
Kishida, Fumio. (2024). Written Answer to the Question about Replicon Vaccine submitted by Mr. Ryuhei Kawada, a member of the House of Councillors. 213th Plenary Session of the Diet, Cabinet Councillor No. 213, July 2, 2024. https://www.sangiin.go.jp/japanese/joho1/kousei/syuisyo/213/touh/t213203.htm
Ministry of Health, Labour and Welfare . (2024). Summary of Minister Takemi's press conference (July 26, 2024, 11:16-11:32, Ministry press conference room). https://www.mhlw.go.jp/stf/kaiken/daijin/0000194708_00722.html
Ricardo-Lax, I., Luna, J. M., Thao, T. T. N., Le Pen, J., Yu, Y., Hoffmann, H. H., ... & Rice, C. M. (2021). Replication and single-cycle delivery of SARS-CoV-2 replicons. Science, 374(6571), 1099-1106. https://doi.org/10.1126/science.abj8430
Seneff, S., & Nigh, G. (2021). Worse than the disease? Reviewing some possible unintended consequences of the mRNA vaccines against COVID-19. International Journal of Vaccine Theory, Practice, and Research, 2(1), 38-79. https://doi.org/10.56098/ijvtpr.v2i1.23
Sheridan, C. (2024). First self-amplifying mRNA vaccine approved. Nature Biotechnology, 42, 4. https://doi.org/10.1038/s41587-023-02101-2
Slawotsky, J. (2023). Leveraging Human Rights Due Diligence in Corporate-State Procurement: The Exemplar of the Pfizer-Israeli COVID-19 Vaccination Program. Human Rights Journal, 8(3), 352-368. https://doi.org/10.1017/bhj.2023.43
Yomiuri Shimbun. (2024-7-21). Routine vaccination with new corona vaccine to begin in October...Voluntary vaccination fee to be paid in full is about 15,000 yen. Yomiuri Shimbun Online. https://www.yomiuri.co.jp/medical/20240721-OYT1T50112/
【緊急声明】
新型コロナウイルス感染症予防接種に導入されるレプリコンワクチンへの懸念 自分と周りの人々のために
要約
一般社団法人日本看護倫理学会は、次世代型 mRNA ワクチンとして、世界で唯一日本のみで認可され、2024 年 10 月 1 日から定期接種を開始するとされている自己増幅型 mRNAワクチン（レプリコンワクチン）の安全性および倫理性に関する懸念を表明します。
はじめに
新型コロナウイルス感染症に対する予防手段として遺伝子操作型ワクチンである mRNAワクチンが導入され、多くの国民が接種しました。
いままでのワクチンが、ウイルスや細菌などの病原体を弱毒化したものやその成分を抗原として接種しヒトの免疫応答を誘導するのに対し、遺伝子操作型ワクチンは、当該抗原 (スパイクタンパク質)をヒトの細胞内の遺伝機構を用いて作らせる点が大きく異なります。
そして、昨年 11 月 28 日に、自己増幅型 mRNA ワクチン（レプリコンワクチン）が世界に先駆けて日本で認可され(CSL, 2023; Sheridan, 2024)、以来日本は世界で唯一の認可国となっています。認可されたレプリコンワクチンは米国の Arcturus Therapeutics が開発し、ベトナムでの大規模な治験（第 I～第 III 相臨床試験）(Ho" et al., 2024)を経て、製造と販売を日本の Meiji Seika ファルマが行なうものです。
レプリコンワクチンは、これまでの mRNA ワクチンの抗原産生機能に加え自分自身を複製する機能があるため、少量の接種で長期間スパイクタンパク質を産生します。このレプリコンワクチンは 2024 年 10 月 1 日をめどに定期接種を開始する(読売新聞, 2024)とされていますが、本学会は以下の通り、このワクチンの安全性・倫理性に関する懸念を表明します。
1. レプリコンワクチンが開発国や先行治験国で認可されていないという問題
日本がレプリコンワクチンを認可してから 8 ヶ月が経過していますが、開発国である米国や大規模治験を実施したベトナムをはじめとする世界各国で未だにレプリコンワクチンが認可されていないのはなぜでしょうか。この状況は、海外で認可が取り消された薬剤を日本で使い続けた結果、多くの健康被害をもたらした薬害事件を思い起こさせます。COVID- 19 パンデミックのときのような緊急時を除き、本来、薬剤は安全性が認められるまで世の中に出回ることはありません。海外で未認可であるということは何らかの安全上の懸念があるのではないかと疑わざるを得ません。
2. シェディングの問題
レプリコンワクチンが「自己複製する mRNA」であるために、レプリコンワクチン自体が接種者から非接種者に感染(シェディング)するのではないかとの懸念があります(Seneff & Nigh, 2021)。すなわちそれは、望まない人にワクチンの成分が取り込まれてしまうという倫理的問題をはらんでいます。これは医療において最も重要で最も基本的な倫理原則である「危害を与えない」ことへの重大な侵害といえます。レプリコンワクチンは、感染性を持たせないように設計されている(Ricardo-Lax et al., 2021)とのことですが、そのことは臨床研究によって実証されなければなりません。しかし、現在までに当該レプリコンワクチンにおけるシェディングに関する臨床研究は皆無(岸田, 2024; 厚生労働省, 2024)です。レプリコンワクチンが、望まない人にワクチンの成分が取り込まれてしまうという倫理的問題をはらんでいることに加え、10 月からの定期接種が、シェディングの有無を確認するための実証研究になってはいけないと考えます。
3. 将来の安全性に関する問題
遺伝子操作型 mRNA ワクチンは、人体の細胞内の遺伝機構を利用し抗原タンパク質を生み出す技術であることから、人間の遺伝情報や遺伝機構に及ぼす影響、とくに後世への影響についての懸念が強く存在します。mRNA ベースのワクチンはヒトの DNA を変化させないという根強い主張がありますが、それを裏付ける研究は欠如しており、出所のはっきりしない仮定である(Domazet-Lošo, 2022)ことが明らかになっています。最近の研究では、ファイザー・ビオンテック製の mRNA ワクチンの塩基配列がヒトの肝細胞の DNA に逆転写されたと報告されており(Aldén et al., 2022)、ヒトの遺伝情報に影響しないという言説は根拠を失いつつあります。このような問題が解決されていない以上、定期接種によって広範囲かつ継続的に mRNA ワクチンを使用することは問題があると考えます。
4. インフォームドコンセントの問題
従来の mRNA ワクチンで指摘されていた重篤な副作用については、臨床試験の段階にお いても(Cardozo & Veazey, 2021)、実際に接種が開始されてからも(Slawotsky, 2023)、被接種者に十分な説明が行われてこなかったことが示されており、インフォームドコンセントを基盤とする医療のあり方を揺るがしかねない事態に私どもは強い懸念をもっています。従来の mRNA ワクチンでも指摘されていた心筋炎(Hviid et al., 2024)やアナフィラキシー (Barta et al., 2024)等に加え、上述したシェディングの可能性など、接種の時点で判明している有害事象のリスクを、被接種者に十分に説明し、理解をしてもらうことが重要です。そのうえで被接種者本人が自発的に承諾するという基本的なインフォームドコンセントのプロセスを経る必要性があると考えます。
5. 接種勧奨と同調圧力の問題
従来の mRNA ワクチン接種の事例を鑑みますと、ひとたびレプリコンワクチンが定期接種化されれば、医療従事者は率先して接種すべきであるとの世論や医療機関の方針が打ち出されることは想像するに難くありません。患者を守るために医療従事者が感染経路とならないようにするという大義名分のもと、医療従事者自身の主体的な自己決定権が脅かされることがあってはなりません。また、レプリコンワクチンは、自分のみならず、非接種者の家族や周囲の人々にまで影響を与える可能性がある中で、接種しなければならない状況に追い込まれることは絶対にあってはならないことだと考えます。
結論
一般社団法人日本看護倫理学会は、レプリコンワクチンの導入に関してはさらなる研究と長期的な安全性データの収集が必要であり、十分なインフォームドコンセントの確保と、接種に関する勧奨と同調圧力の排除が求められると考えます。われわれは、安全かつ倫理的に適切なワクチンの開発と普及を強く支持するものではありますが、そのいずれも担保されていない現段階において拙速にレプリコンワクチンを導入することには深刻な懸念を表明します。
2024 年 8 月 7 日一般社団法人日本看護倫理学会
理事長 前田樹海
Aldén, M., Olofsson Falla, F., Yang, D., Barghouth, M., Luan, C., Rasmussen, M., & De Marinis, Y. (2022). Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell
line. Current issues in molecular biology, 44(3), 1115-1126. https://doi.org/10.3390/cimb44030073
Barta, B. A., Radovits, T., Dobos, A. B., Kozma, G. T., Mészáros, T., Berényi, P., ... & Szebeni, J. (2024). Comirnaty- induced cardiopulmonary distress and other symptoms of complement-mediated pseudo-anaphylaxis in a hyperimmune pig model: Causal role of anti-PEG antibodies. Vaccine: X, 19, 100497. https://doi.org/10.1016/j.jvacx.2024.100497
Cardozo, T., & Veazey, R. (2021). Informed consent disclosure to vaccine trial subjects of risk of COVID-19 vaccines worsening clinical disease. International journal of clinical practice, 75(3), e13795. https://doi.org/10.1111/ijcp.13795
CSL. (2023). Japan's Ministry of Health, Labour and Welfare Approves CSL and Arcturus Therapeutics' ARCT-154, the first Self-Amplifying mRNA vaccine approved for COVID in adults. CSL News Releases. https://newsroom.csl.com/2023-11-28-Japans-Ministry-of-Health,-Labour-and-Welfare-Approves-CSL-and-Arcturus- Therapeutics-ARCT-154,-the-first-Self-Amplifying-mRNA-vaccine-approved-for-COVID-in-adults
Domazet-Lošo T. (2022). mRNA Vaccines: Why Is the Biology of Retroposition Ignored? Genes. 13(5),719. https://doi.org/10.3390/genes13050719
Hviid, A., Nieminen, T. A., Pihlström, N., Gunnes, N., Dahl, J., Karlstad, Ø., ... & Hovi, P. (2024). Booster vaccination with SARS-CoV-2 mRNA vaccines and myocarditis in adolescents and young adults: a Nordic cohort
study. European Heart Journal, 45(15), 1327-1335. https://doi.org/10.1093/eurheartj/ehae056
Ho", N. T., Hughes, S. G., Ta, V. T., Phan, L. T., Đo$, Q., Nguye$n, T. V., ... & Nguyen, X. H. (2024). Safety,
immunogenicity and efficacy
of the self-amplifying mRNA ARCT-154
COVID-19 vaccine: pooled phase 1, 2, 3a and
3b randomized, controlled trials. Nature Communications, 15(1), 4081. https://doi.org/10.1038/s41467-024-47905-1
岸田文雄. (2024). 参議院議員川田龍平君提出レプリコンワクチンに関する質問に対する答弁書. 第 213 回国会(常会) 内閣参質二一三第二〇三号 令和六年七月二日. https://www.sangiin.go.jp/japanese/joho1/kousei/syuisyo/213/touh/t213203.htm
厚生労働省. (2024). 武見大臣会見概要(令和 6 年 7 月 26 日（金）11:16～11:32 省内会見室). https://www.mhlw.go.jp/stf/kaiken/daijin/0000194708_00722.html
Ricardo-Lax, I., Luna, J. M., Thao, T. T. N., Le Pen, J., Yu, Y., Hoffmann, H. H., ... & Rice, C. M. (2021). Replication and single-cycle delivery of SARS-CoV-2 replicons. Science, 374(6571), 1099-1106. https://doi.org/10.1126/science.abj8430
Seneff, S., & Nigh, G. (2021). Worse than the disease? Reviewing some possible unintended consequences of the mRNA vaccines against COVID-19. International Journal of Vaccine Theory, Practice, and Research, 2(1), 38-79. https://doi.org/10.56098/ijvtpr.v2i1.23
Sheridan, C. (2024). First self-amplifying mRNA vaccine approved. Nature Biotechnology, 42, 4. https://doi.org/10.1038/s41587-023-02101-2
Slawotsky, J. (2023). Leveraging Human Rights Due Diligence in Corporate-State Procurement: The Exemplar of the Pfizer-Israeli COVID-19 Vaccination Program. Business and Human Rights Journal, 8(3), 352-368. https://doi.org/10.1017/bhj.2023.43
読売新聞. (2024-7-21). 新型コロナワクチンの定期接種、10 月から開始…全額自己負担の任意接種費は 1 万 5000 円程度. 読売新聞オンライン. https://www.yomiuri.co.jp/medical/20240721-OYT1T50112/
