Mpox 暴露之後疫苗接種後的突破性感染

資料來源：n engl j med nejm.org / DOI: 10.1056/NEJMc2211944 / 葉財團法人台灣紅絲帶基金會編譯

致編輯：在當前猴痘（最近更名為 mpox）爆發期間，已建議接種天花疫苗以預防接觸過 mpox 的人感染 mpox，但支持這種做法的證據有限。我們進行了一項研究以評估在高危接觸 mpox 後接種天花疫苗的參與者的潛在突破性感染。

   從 2022 年 5 月 27 日到 7 月 13 日，我們進行了一項單中心觀察分析，涉及所有的參與者  在高危 mpox 暴露後連續接受皮下 0.5 毫升劑量（標稱滴度為 5×107 TCID50 [50% 組織培養感染劑量])）的第三代天花疫苗（JYNNEOS [Imvanex]）。這些接觸被定義為與感染者直接皮膚接觸或粘膜接觸、間接接觸、接觸呼吸道飛沫或所有這些接觸。從所有參與者那裡獲得了書面知情同意書，並經巴黎北部索邦大學倫理委員會批准了這項研究。

   共有 276 名參與者在暴露後 11 天（四分位距，8 至 14 天）接種了一劑疫苗。 共有 114 名參與者 (41%) 有兩種重疊的暴露類型——主要是間接暴露加暴露於呼吸道飛沫（78 名參與者 [28%]）和直接暴露加暴露於呼吸道飛沫（28 名參與者 [10%] ) ；102 名參與者 (37%) 有所有三種類型的暴露（直接暴露、間接暴露和呼吸飛沫暴露）。在 276 名接種疫苗的參與者中，233 名 (84%) 是男男性行為者，前一個月性伴侶的中位數為 8 人（四分位距，3 至 13 人）。沒有發現嚴重的不良事件或安全問題。 276 名接種疫苗的參與者中有 12 名 (4%) 隨後被證實為非嚴重性的 mpox 感染；在這些參與者並後續感染者中，有4 人 (33%) 的人類免疫缺陷病毒感染控制良好（相較之下，在接種疫苗且未感染的人中，264 人中有 33 人 [12%]）；後續感染之12人中的2 人 (17%) 有天花疫苗接種史（相較之下，在接種疫苗但未感染的人群中，264 人中有 28 人 [11%]）。接種疫苗後 5 天內，12 名參與者中有 10 名發生了 Mpox 感染，22 天時有 1 名參與者發生了 Mpox 感染，25 天時有 1 名參與者發生了 Mpox 感染（圖 1）。未發生 mpox 感染的參與者在中位數 29 天（四分位距，28 至 33 天）後接受了第二劑疫苗。

   早期感染可能是由於暴露和疫苗接種之間的延遲（中位數，11 天），因為 mpox 的潛伏期為 5 到 21 天，但這些感染也增加了早期暴露的可能性。在第 22 天和第 25 天發生突破性感染的兩名參與者表示他們沒有新的接觸，但他們是唯一擁有寵物的參與者（一隻貓和一隻狗都沒有症狀並且與參與者同住但沒有和他們一起睡覺）。

我們的研究有幾個局限性。它是在一個中心進行的，我們無法評估 mpox 的暴露情況。此外，該研究採用開放標籤設計，沒有對照組或疫苗引發的免疫之量測方法，外部有效性有限。

   在該研究人群中，接受過第三代天花疫苗暴露後疫苗接種的參與者中有 4% 在接受第一次疫苗接種後的第一個月內發生了隨後的 mpox 感染。

圖 1. 接觸、疫苗接種和確認的 Mpox 感染。

暴露被定義為參與者與確認 mpox 的感染者（透過聚合酶鏈反應測定）有直接皮膚接觸或粘膜接觸，間接接觸受污染的紡織品或其他表面，接觸呼吸道飛沫（透過與不戴口罩的感染者保持一定距離接觸<2 m ≥ 3 小時），或所有這些暴露。 參與者 6 是一名醫護人員，他在工作中意外針刺傷後感染。 補充附錄中的結果部分提供了更多詳細信息。IQR 表示四分位間距。

Michael Thy，醫學博士 ；Nathan Peiffer Smadja，醫學博士，哲學博士；巴黎大學，法國巴黎 michael.thy@aphp.fr 

Morgane Mailhe，醫學博士 ；Laura Kramer，藥學博士 ；Bichat-Claude Bernard 醫院，法國巴黎 Valentine M. Ferré，醫學博士，巴黎大學，法國巴黎；

Nadhira Houhou，醫學博士；Hassan Tarhini，醫學博士；Chloé Bertin，醫學博士； Anne Lise Beaumont，醫學博士 ；Mathilde Garé，醫學博士 ；Diane Le Pluart，醫學博士 ；Ségolène Perrineau，醫學博士； Mayda Rahi、醫學博士； Laurène Deconinck、醫學博士 ；Bao Phung、醫學博士 ；Bastien Mollo、醫學博士 ；Marie Cortier、醫學博士； Mélanie Cresta、醫學博士 ；Clémentine De La Porte Des Vaux、醫學博士； Véronique Joly、醫學博士； Sylvie Lariven，醫學博士；Christophe Rioux，醫學博士；Bichat-Claude Bernard 醫院，法國巴黎

Cécile Somarriba，醫學博士，Agence Régionale de Santé 法蘭西島 ，法國巴黎

Francois‑Xavier Lescure，醫學博士，哲學博士；Charlotte Charpentier，醫學博士，哲學博士；

Yazdan Yazdanpanah，醫學博士，哲學博士；Jade Ghosn，醫學博士，哲學博士 ；巴黎西堤大學，法國巴黎

Yazdanpanah 和 Ghosn 對此文做出了同等貢獻

作者提供的披露表格呈現於NEJM.org 上這封信的全文中。

這封信於 2022 年 12 月 7 日在 NEJM.org 上發表。

Breakthrough Infections after Postexposure Vaccination against Mpox

n engl j med nejm.org

To the Editor: During the current outbreak of monkeypox (recently renamed mpox), smallpox vaccination has been recommended to prevent mpox infection in persons who have had mpox exposure, but evidence to support this practice is limited. We conducted a study to evaluate potential breakthrough infections in participants who had received smallpox vaccine after high-risk exposure to mpox.

  From May 27 through July 13, 2022, we performed a single-center observational analysis involving all consecutive participants who had received a third-generation smallpox vaccine (JYNNEOS [Imvanex]) at a subcutaneous 0.5-ml dose (a nominal titer of 5×107 TCID50 [50% tissueculture infectious dose]) after a high-risk mpox exposure. These exposures were defined as direct skin-to-skin or mucosal contact with an infected person, indirect contact, exposure to respiratory droplets, or all of these exposures (definitions are provided in the Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Written informed consent was obtained from all the participants. The ethics committee of the Sorbonne Paris North University approved the study.

  A total of 276 participants had received one dose of vaccine 11 days (interquartile range, 8 to 14) after exposure. A total of 114 participants (41%) had two overlapping types of exposure — mainly indirect exposure plus exposure to respiratory droplets (in 78 participants [28%]) and direct exposure plus exposure to respiratory droplets (in 28 participants [10%]) — and 102 participants (37%) had all three types of exposure (direct exposure, indirect exposure, and exposure to respiratory droplets) (Table S1 in the Supplementary Appendix). Among the 276 vaccinated participants, 233 (84%) were men who had sex with men, with a median of 8 sexual partners (interquartile range, 3 to 13) in the previous month. No severe adverse events or safety concerns were identified. Twelve of the 276 vaccinated participants (4%) had a subsequent confirmed nonsevere mpox infection; of these participants, 4 (33%) had well-controlled human immunodeficiency virus infection (as compared with 33 of 264 [12%] among those who were vaccinated and uninfected) and 2 (17%) had a history of smallpox vaccination (as compared with 28 of 264 [11%] among those who were vaccinated and uninfected). Mpox infection developed in 10 of the 12 participants within 5 days after vaccination, in 1 participant at 22 days, and in 1 participant at 25 days (Fig. 1). The participants in whom mpox infection did not develop received a second dose of vaccine after a median of 29 days (interquartile range, 28 to 33).

  Early infections may be explained by the delay between exposure and vaccination (median, 11 days) because the incubation of mpox ranges from 5 to 21 days, but these infections also raise the possibility of an earlier exposure. The two participants with breakthrough infections at 22 and 25 days indicated that they had not had a new exposure, but they were the only participants who had a pet (one cat and one dog that were both asymptomatic and that shared the participants’ homes but did not sleep with them). Our study has several limitations. It was conducted at a single center, and we were not able to assess exposure to mpox. In addition, the study had an open-label design, did not have a control group or measures of vaccine-elicited immunity, and had limited external validity.

  In this study population, 4% of the participants who had received postexposure vaccination with a third-generation smallpox vaccine had a subsequent mpox infection during the first month after receipt of the first vaccination.

Michael Thy, M.D. Nathan Peiffer Smadja, M.D., Ph.D. Université de Paris Cité Paris, France michael.thy@aphp.fr Morgane Mailhe, M.D. Laura Kramer, Pharm.D. Bichat–Claude Bernard Hospital Paris, France Valentine M. Ferré, M.D. Université de Paris Cité Paris, France Nadhira Houhou, M.D. Hassan Tarhini, M.D. Chloé Bertin, M.D. Anne Lise Beaumont, M.D. Mathilde Garé, M.D. Diane Le Pluart, M.D. Ségolène Perrineau, M.D. Mayda Rahi, M.D. Laurène Deconinck, M.D. Bao Phung, M.D. Bastien Mollo, M.D. Marie Cortier, M.D. Mélanie Cresta, M.D. Clémentine De La Porte Des Vaux, M.D. Véronique Joly, M.D 

Sylvie Lariven, M.D. Christophe Rioux, M.D. Bichat–Claude Bernard Hospital Paris, France Cécile Somarriba, M.D. Agence Régionale de Santé Ile-de-France Paris, France Francois Xavier Lescure, M.D., Ph.D. Charlotte Charpentier, M.D., Ph.D. Yazdan Yazdanpanah, M.D., Ph.D. Jade Ghosn, M.D., Ph.D. Université de Paris Cité Paris, France Drs. 

Yazdanpanah and Ghosn contributed equally to this letter. 

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. 

This letter was published on December 7, 2022, at NEJM.org.