1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China 2. Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
Corresponding Author(s):
Jie Wu,Hangping Yao,Lanjuan Li
引用本文:
. [J]. Frontiers of Medicine, 2022, 16(4): 507-517.
Miaojin Zhu, Jia Ji, Danrong Shi, Xiangyun Lu, Baohong Wang, Nanping Wu, Jie Wu, Hangping Yao, Lanjuan Li. Unusual global outbreak of monkeypox: what should we do?. Front. Med., 2022, 16(4): 507-517.
Inhibits the activity of the orthopoxvirus VP37 envelope wrapping protein and prevents virus replication and intracellular viruses release
PO, IVAdults: 600 mg twice daily for 14 daysPediatrics (13 kg or more): dosage reduction
The completed phase 3 clinical trials to evaluate the safety, tolerability, and pharmacokinetics of tecovirimat showed the drug was safe with minor side effects
Licensed by FDA for the treatment of human smallpox disease since July 2018 and urgently licensed by FDA for treatment of monkeypox in 2022
[61,62]
Brincidofovir
Chimerix
Phosphorylated cidofovir diphosphate acts as a competitive substrate inhibitor of DNA polymerase to reduce DNA synthesis and terminating chain elongation
POMost frequently administered at an oral dose of 200 mg twice weekly
The completed phase 1/2/3 clinical trials showed the drug had effective antiviral effects and the main dose-limiting toxic effects are gastrointestinal events
Licensed by FDA for treatment of human smallpox disease in adult and pediatric patients in the US since June 2021
[63,64]
Cidofovir
Gilead
Inhibits CMV replication by selective inhibition of viral DNA polymerase, thereby preventing viral replication and transcription
IV5 mg/kg once weekly for the first 2 weeks, and thereafter once every other week
The completed phase 2/3 clinical trials to evaluate the effectiveness, safety of cidofovir in AIDS patients with CMV retinitis showed the drug was effective, but with the potential risk of nephrotoxicity
Developed for the treatment of cytomegalovirus retinitis in patients with AIDS, which has been used in the treatment of poxvirus infections
[65–67]
Blood products
Vaccinia Immune Globulin
Cangene Corporation/ DynPort Vaccine
Antibodies isolated from blood of healthy adults vaccinated with vaccinia neutralize the virus to inhibit viral infection and provide passive immunity
IVSevere complications of vaccinia vaccination: 6000 U/kg with a maximum speed of 2 mL/min as soon as symptoms appearPersistent or severe symptoms: considered repeated administration
An open-label phase 4 study is under way to collect additional data to assess the safety and efficacy of VIGIV in healthy people
Licensed by FDA for the treatment of complications caused by vaccinia vaccination since February 2005, considered emergency treatment of orthopoxviruses in the case of a serious outbreak
[68,69]
Vaccines
MVA-BN
Bavarian Nordic
Based on a live, highly attenuated vaccinia virus, unable to achieve complete replication in humans but can induce an effective immune response
IHA total of 2 doses (0.5 mL per dose) were injected subcutaneously with an interval of 4 weeksSubjects previously vaccinated against smallpox: a single 0.5 mL dose
The completed phase 2/3 clinical trials showed it had excellent safety and tolerability in both healthy and low immunity people, and its immunogenicity was not inferior to ACAM2000
Licensed by FDA to prevent monkeypox in September 2019, applicable to adults over 18 years old with high risk of monkeypox infection
[70–73]
ACAM2000
Acambis
A live, replication-competent vaccinia virus vaccine derived from a plaque-purified clone can induce an effective immune response
TDDAdministered in a single 2.5 μL dose by the percutaneous route (scarification) using 15 jabs bifurcated needle to the deltoid muscle of the upper arm
The completed phase 1/2/3 clinical trials have shown it had excellent immunogenicity and safety, but with the concerns about the incidence of vaccination-related myopericarditis
Licensed by FDA for people at high risk of exposure to smallpox since August 2007
[70,74,75]
APSV
Aventis Pasteur
A liquid formulation of calf-lymph vaccine produced by vaccinia virus derived from the NYCBOH strain can induce an effective immune response
TDDAdministered in a single 2.5 μL dose by the percutaneous route (scarification) using 15 jabs bifurcated needle to the deltoid muscle of the upper arm
The completed phase 1/2 clinical trials to evaluate the safety, dose and preliminary efficacy of APSV in vaccinia-naive adults showed it was still effective at diluted doses, but its reactogenicity did not decrease
Submitted a pre-EUA to FDA for the use of APSV diluted 1:5 to vaccinate persons during a declared public health emergency involving smallpox
[70,76]
Tiantan
Sinopharm
A live, highly attenuated vaccinia virus isolated from the blister scab of patients with smallpox in 1926 can induce an effective immune response
TDDAdministered in a single 10 μL dose by the acupuncture or scarification route inoculation on the deltoid muscle of the upper arm
The completed phase 2 clinical trials of recombinant Tiantan vaccinia virus-vectored/HIV-1 booster in healthy people showed excellent performance in immunogenicity and safety
Licensed for use in China. Novel smallpox vaccines constructed by deleting some genes of Tiantan strain, have been used in the research of vaccines such as HIV, HBV, HCV and so on
[77–80]
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