元々、「SARSに対して、mRNAワクチンを試すのはADEを発生させるから危険だ」というのは、猫での実験ではほとんどでADEが発生したほか、治験中のmRNAワクチンで子どもが死んでいるからです。実際、SARSに対するmRNAワクチンの開発は断念されました。興味のある人は「Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus」という論文をお読みください。

そして、今回のmRNAワクチンでも、「コロナワクチンを接種した人がデルタ株に感染した場合、ADEを生ずる可能性がある」ことを示した論文が出ました。その論文は、「Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination?」(Journal of Infection)で、「ADE may occur in people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors) and then exposed to a Delta variant. ・・・Since our data indicate that Delta variants are especially well recognized by infection enhancing antibodies targeting the NTD, the possibility of ADE should be further investigated as it may represent a potential risk for mass vaccination during the current Delta variant pandemic」と結論付けています。


―― ワクチンを接種したことで新型コロナウイルス感染症の症状が悪化するかもしれないと指摘する研究論文が発表され、注目されている。今月9日に学術誌「Journal of Infection」に発表されたフランス・エクス=マルセイユ大学の研究者らによる研究で、現在流行しているデルタ株に対し「抗体依存性感染増強(ADE)」という現象が起こる可能性があることがわかった。ADEとは、ワクチンによって作られた抗体が、免疫細胞などへのウイルスの感染を促進し、症状を悪化させてしまうという現象だ。・・・今回の研究では、デルタ株に関して、ウイルスのトレードマークであるスパイクタンパク質に対する親和性が「驚くほど高まった」ことにより、ワクチンが感染を促進したと考えられるという。また、今年3月には、専門家向け医療情報サイト「MedPage Today」の記事でも、「ADEは中和抗体(ウイルスと結合して感染を阻止する抗体)の存在量が十分に少なく、感染を防ぐことができない場合にも起こる可能性がある。それどころか、ウイルス粒子と免疫複合体を形成してしまい、かえって病気を悪化させる」と指摘されていた。一方、新型コロナウイルスに感染し、自然免疫を獲得した人の間ではADEのような問題は見られないことが複数の研究で示されているという。


PLoS One. April 20, 2012

Background: Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.

Design: Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated i.m. on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.

Results: All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.

Conclusions: These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was inducedCaution in proceeding to application of a SARS-CoV vaccine in humans is indicated.

The emergence of the disease SARS and the rapid identification of its severity and high risk for death prompted a rapid mobilization for control at the major sites of occurrence and at the international level. Part of this response was for development of vaccines for potential use in control, a potential facilitated by the rapid identification of the causative agent, a new coronavirus. Applying the principles of infection control brought the epidemic under control but a concern for reemergence naturally or a deliberate release supported continuation of a vaccine development effort so as to have the knowledge and capability necessary for preparing and using an effective vaccine should a need arise. For this purpose, the National Institute of Allergy and Infectious Diseases supported preparation of vaccines for evaluation for potential use in humans. This effort was hampered by the occurrence in the initial preclinical trial of an immunopathogenic-type lung disease among ferrets and Cynomolgus monkeys given a whole virus vaccine adjuvanted with alum and challenged with infectious SARS-CoV. That lung disease exhibited the characteristics of a Th2-type immunopathology with eosinophils in the lung sections suggesting hypersensitivity that was reminiscent of the descriptions of the Th2-type immunopathologic reaction in young children given an inactivated RSV vaccine and subsequently infected with naturally-occurring RSV. Most of these children experienced severe disease with infection that led to a high frequency of hospitalizations; two children died from the infection. The conclusion from that experience was clear; RSV lung disease was enhanced by the prior vaccination.

➡ コロナ問題やワクチン問題を、科学的・体系的に理解したい方は、「科学的事実①:はじめに」から「新型コロナウイルス感染症に関する科学的事実(第三版:2021.5.24)」をお読みください。