「症例報告：217回の新型コロナウイルスワクチン接種は人間の免疫系に悪影響を及ぼさなかった」https://t.co/skqJPxrCjq
— Dr. Tad (@tak53381102) March 5, 2024
これは無意味な行為であり詐欺行為は許されないことだが、免疫機能が正常に維持されていることは純粋に驚く… pic.twitter.com/zzFtVT88MZ
What would happen if you got vaccinated against the same antigen over and over again? In @TheLancetInfDis, we now report on a hypervaccinated individual from Magdeburg (HIM) who received 217 vaccinations within 29 months against SARS-CoV-2. 👇 1/19 https://t.co/or1gLBFDgk
— Kilian Schober (@kischober) March 5, 2024
When, in 2022, the media reported about a man from Germany who received at least 90 vaccinations against SARS-CoV-2, we (as many others) wondered what kind of consequences such hypervaccination would have on the immune system. 2/19 pic.twitter.com/U7CvK4wKv9
— Kilian Schober (@kischober) March 5, 2024
HIM underwent hypervaccination for private reasons outside of a clinical study context & against national vaccination recommendations. The public prosecutor of Magdeburg opened an investigation of HIM's case with the allegation of fraud, but criminal charges were not filed. 3/19
— Kilian Schober (@kischober) March 5, 2024
108 vacc. are individually recorded and partly overlap with a total of 130 prosecutor-confirmed vacc. In total, we have confirmation for 134 out of 217 vacc. We started sampling after the 215th vacc. in Erlangen, but could access sera & results from pre 214th vacc. onwards. 4/19 pic.twitter.com/QgKhS4CwPs
— Kilian Schober (@kischober) March 5, 2024
HIM did not report any vacc.-related side effects. From 2019-2023, 62 routine clinical chemistry parameters showed no abnormalities attributable to hypervaccination. Notably, HIM had no signs of a past SARS-CoV-2 infection as indicated through various repeatedly neg. tests. 5/19 pic.twitter.com/SzH1wX985J
— Kilian Schober (@kischober) March 5, 2024
Compared to 3-dose mRNA reference cohort, HIM's spike-specific IgG were on a record high, but contraction kinetics were normal. Boosting after 217th vacc. worked fine. At a comparable time point, serum neutralization capacity was up 5.4x vs. WT or 11.5x vs. Omicron B1.1.529. 6/19 pic.twitter.com/fCZeruWPky
— Kilian Schober (@kischober) March 5, 2024
We previously reported that repetitive mRNA vaccination induces IgG4 subclass switching. Remarkably, HIM did not show a higher fraction of IgG4 antibodies than controls. Is this due to his 1st vacc. being J&J and many additional early vacc. being AZ? We don’t know. 7/19 pic.twitter.com/gfuwGjOpr7
— Kilian Schober (@kischober) March 5, 2024
In saliva, HIM had detectable anti-spike IgG levels, unlike the control participants. In individuals with high levels of IgG in serum (like HIM) we sometimes see this, perhaps reflecting transcytosis into mucosa. IgA was generally (controls or HIM) not detectable in saliva. 8/19 pic.twitter.com/i6XCtnccYn
— Kilian Schober (@kischober) March 5, 2024
Spike-specific B cells were only mildly elevated and had a similar phenotype as B cells from controls (CD27+ memory). Notably, we did not observe a higher degree of clonal B cell expansion or somatic hypermutation rates. 9/19 pic.twitter.com/N2xMbahKKT
— Kilian Schober (@kischober) March 5, 2024
Like antibodies, spike (A*01/LTD)-specific CD8+ T cells were elevated (about 6x) and could also be boosted by vacc. #217. The T-cell phenotype showed a relative bias towards more differentiated cells. However, importantly, absolute numbers of stem-like cells were similar. 10/19 pic.twitter.com/NPKkjzitcY
— Kilian Schober (@kischober) March 5, 2024
In line with the phenotypic data, the proliferation capacity of spike-specific T cells was normal. Cytokine secretion assays confirmed that more antigen-reactive T cells were present in HIM's blood compared to controls, but on a per-cell-basis, functionality was equal. 11/19 pic.twitter.com/h5GqbboMv6
— Kilian Schober (@kischober) March 5, 2024
Single-cell RNA seq (with VDJseq + CITEseq for 130 proteins and different epitope DNA-barcoded pMHC multimers) confirmed a more differentiated T-cell phenotype and revealed a higher degree of clonal expansion compared to controls. SCENITH showed a normal metabolic profile. 12/19 pic.twitter.com/kU66nfaQjK
— Kilian Schober (@kischober) March 5, 2024
As an important internal control, EBV (B*08/RAK) epitope-specific T-cells were similar in size and phenotype compared to control donors. This also indicates that hypervaccination did not affect responses towards other antigens. 13/19 pic.twitter.com/9RKnsm4S2v
— Kilian Schober (@kischober) March 5, 2024
Finally, analysis of spike-reactive CD4+ T cells confirmed a lack of nucleocapsid-specific immunity and showed similar amounts of cytokine producing CD4+ T cells in HIM compared with the control group, with preserved peptide sensitivity. 14/19 pic.twitter.com/msdZXIE6ee
— Kilian Schober (@kischober) March 5, 2024
In summary, this case (n=1) shows that hypervacc. did not lead to adverse events and increased the quantity of adaptive immunity without a strong positive or negative effect on the quality. While HIM remains SARS-CoV-2 infection-free, any causal association cannot be made. 15/19
— Kilian Schober (@kischober) March 5, 2024
It should go without saying that we do not endorse hypervaccination. Putative positive immunological effects cannot be justified by the number of medical interventions that each vaccination represents. 16/19
— Kilian Schober (@kischober) March 5, 2024
Extreme settings like the one we report here are rare and therefore, almost inevitably, individual cases. The generalizability is thus, of course, unclear. However, we can still learn from such settings which consequences hyperimmunization can have on human immunity. 17/19
— Kilian Schober (@kischober) March 5, 2024
This work was made possible only by a huge team effort @UniFAU. My sincere gratitude goes to leading authors Katharina Kocher, Carolin Moosmann, @ev_schuster and the whole lab as well as all collaborators @DrostFelix, @schubert_benni, @BockLab and others not on X. 18/19 pic.twitter.com/yLJYbsOXMm
— Kilian Schober (@kischober) March 5, 2024
We are also grateful, naturally, to HIMself, but also to Siegfried Krell (Med. Labor Bremen) as well as @BMBF_Bund, @Covim_Netzwerk, @dfg_public (@GRK2504FAU) & @EKFStiftung for supporting this work. Funders had no influence on the study design and data interpretation. 🙏 19/19
— Kilian Schober (@kischober) March 5, 2024
Here's the English @UniFAU press release: https://t.co/GHyf6RJ9ik und hier ist die deutsche Pressemitteilung: https://t.co/sSozdniZSl
— Kilian Schober (@kischober) March 5, 2024
ドイツからCOVID-19ワクチンを29ヶ月に"個人的な事情"で217回接種した62歳男性の症例報告。
— Sukuna (@SukunaBikona7) March 5, 2024
明らかな有害事象はなく、S蛋白特異的な抗体やT細胞数は多く、感染歴はなかったと。
IgG4の割合は対照群よりも高くはなかったと。https://t.co/hhlycBNbVq
29ヶ月間で217回の新型コロナワクチンを接種した62歳男性の1例．副反応は特になく，血液データにも異常なし．新型コロナウイルス感染はなく，抗スパイク蛋白IgG抗体価や中和抗体価は通常接種者より高かった．免疫応答の質は通常接種と変わらず，耐性獲得もなし．（Lancet Infect Dis 2024 Mar.4） pic.twitter.com/0bDbAUq52z
— EARLの医学ツイート (@EARL_med_tw) March 5, 2024
話題の新型コロナワクチンを217回接種したドイツの男性の研究(Lancet Infectious Diseases)
— 大津秀一🍀医師🍀緩和ケア内科🍀早期からの緩和ケア外来🍀院長🍀「どこでも緩和®」で全国対応可 (@shuichiotsu) March 6, 2024
・本例では目立った有害事象認めず
・免疫の疲弊も認めず
・IgG4量は増えたがIgG全体の中での比率は正常範囲
・新型コロナへの抗体とT細胞は増加
・他病原体への免疫系の有効性に変化なし
と注目される結果
・出典https://t.co/9xDzu8byD9
— 大津秀一🍀医師🍀緩和ケア内科🍀早期からの緩和ケア外来🍀院長🍀「どこでも緩和®」で全国対応可 (@shuichiotsu) March 6, 2024
推奨範囲を超えた、本例のような過剰な回数の接種は勧められない点は研究者も強調している
ただ、接種を繰り返すと、免疫が疲弊する、他の感染症に対して脆弱となる等の説が一部に流れていたが、217回の接種でもそれらの証拠を認めなかったという点は注目される
・本研究に関するプレスリリース 「他の病原体に対する免疫系の有効性には変化がない」https://t.co/zLcSBaqMQG
— 大津秀一🍀医師🍀緩和ケア内科🍀早期からの緩和ケア外来🍀院長🍀「どこでも緩和®」で全国対応可 (@shuichiotsu) March 6, 2024
接種が重なることで、免疫が疲弊する、他の病原体への免疫が脆弱化するなどの説を本研究は否定する結果だった。その点でまた新たな知見が得られたとは言えるだろう
