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Cell Mar 2024In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly...
In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).
Topics: Animals; Humans; Mice; Macaca fascicularis; Monkeypox virus; Mpox (monkeypox); Smallpox Vaccine; Vaccines, Combined; Vaccinia virus
PubMed: 38366591
DOI: 10.1016/j.cell.2024.01.017 -
Medicine Sep 2022The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other... (Review)
Review
The human monkeypox is an emerging zoonotic orthopoxvirus with a clinical presentation similar to that of smallpox. It is difficult to differentiate monkeypox from other orthopedic infections, and laboratory diagnosis is the primary component of disease identification and monitoring. However, current diagnostics are time-consuming, and new tests are needed for rapid and precise diagnosis. Most cases have been reported in Central Africa; however, an increasing number of cases have been reported in Europe, the United States of America (USA), Australia, and the United Arab Emirates. Although investigation of the current global outbreak is still ongoing, viral transmission seems to have occurred during crowded events in Spain and Belgium. New therapeutics and vaccines are being deployed for the treatment and prevention of monkeypox, and more research on the epidemiology, biology, and ecology of the virus in endemic areas is required to understand and prevent further global outbreaks.
Topics: Australia; Disease Outbreaks; Europe; Humans; Mpox (monkeypox); Monkeypox virus; United States
PubMed: 36107544
DOI: 10.1097/MD.0000000000030406 -
Viruses Dec 2022Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication... (Review)
Review
Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss of immunity against not only smallpox but also other zoonotic orthopoxvirus infections in humans over the past years. An increasing number of human infections with zoonotic orthopoxviruses and, first of all, monkeypox, force us to reconsider a possible re-emergence of smallpox or a similar disease as a result of natural evolution of these viruses. The review contains a brief analysis of the results of studies on genomic organization and evolution of human pathogenic orthopoxviruses, development of modern methods for diagnosis, vaccination, and chemotherapy of smallpox, monkeypox, and other zoonotic human orthopoxvirus infections.
Topics: Animals; Humans; Smallpox; Mpox (monkeypox); Variola virus; Poxviridae Infections; Orthopoxvirus; Zoonoses; Monkeypox virus
PubMed: 36680142
DOI: 10.3390/v15010103 -
Epidemiology and Health 2022Monkeypox, a rare zoonotic disease, is primarily prevalent in Central and Western Africa. However, monkeypox is emerging as a worldwide concern due to the 2022 monkeypox... (Review)
Review
Monkeypox, a rare zoonotic disease, is primarily prevalent in Central and Western Africa. However, monkeypox is emerging as a worldwide concern due to the 2022 monkeypox outbreak, which is the first instance of widespread community transmission outside Africa. Monkeypox is caused by the monkeypox virus, which belongs to the genus Orthopoxvirus and presents as a vesicular-pustular disease that may be preceded by fever, malaise, and other constitutional symptoms. If present, lymphadenopathy may distinguish it from chickenpox or smallpox. However, contrary to previous manifestations, most monkeypox patients presented with atypical features during the 2022 outbreak. Monkeypox is usually a self-limiting disease with symptoms lasting between 2 weeks and 4 weeks and is mainly transmitted when a person comes into contact with an infected animal, person, or fomites contaminated with the virus. Very few treatment options are available for this disease. Tecovirimat has been licensed in some countries for the treatment of smallpox and monkeypox infections. Two other medications, cidofovir and brincidofovir, have been found to be effective against poxviruses in in vitro and animal studies, but data on human cases of monkeypox are limited. Although Imvamune (JYNNEOS), a vaccine against monkeypox, is authorized in the United States, there are currently no established routine vaccination programs. Current preventive strategies focus on the detection of probable cases and containment of the outbreak through the implementation of selected ring vaccination programs. Fundamental principles to prevent the spread of monkeypox, including maintaining personal hygiene and avoiding close contact with symptomatic patients, are of paramount importance.
Topics: Animals; Humans; Mpox (monkeypox); Smallpox; Monkeypox virus; Cidofovir; Disease Outbreaks
PubMed: 36228673
DOI: 10.4178/epih.e2022082 -
Emerging Microbes & Infections Dec 2023Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines...
Current unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.
Topics: Animals; Mice; Antibodies, Viral; Orthopoxvirus; Viral Envelope Proteins; Mpox (monkeypox); Antibodies, Neutralizing; Vaccinia virus
PubMed: 37070521
DOI: 10.1080/22221751.2023.2204151 -
World Journal of Pediatrics : WJP Mar 2023The objective of this paper is to analyze the current status of monkeypox worldwide. In the face of this public health threat, our purpose is to elucidate the clinical... (Review)
Review
BACKGROUND
The objective of this paper is to analyze the current status of monkeypox worldwide. In the face of this public health threat, our purpose is to elucidate the clinical characteristics and epidemiology of monkeypox, the developmental progress of monkeypox-related drugs and the vaccines available.
DATA SOURCES
The literature review was performed in databases including PubMed, Science Direct and Google Scholar up to July 2022.
RESULTS
Since May 2022, the World Health Organization has reported more than 45,000 confirmed cases from 92 nonendemic countries, including nine deaths. Although some women and children have been infected so far, most cases have occurred among men who have sex with other men, especially those with multiple sexual partners or anonymous sex.
CONCLUSIONS
Pediatric monkeypox infection has been associated with a higher likelihood of severe illness and mortality than in adults. Severe monkeypox illness in pediatrics often requires adjunctive antiviral therapy. It is crucial for all countries to establish sound monitoring and testing systems and be prepared with emergency preparedness.
Topics: Adult; Male; Female; Humans; Child; Monkeypox virus; Mpox (monkeypox); Databases, Factual; Public Health; World Health Organization
PubMed: 36214966
DOI: 10.1007/s12519-022-00618-1 -
Microbial Pathogenesis Mar 2023While monkeypox was previously found in Africa, the bulk of occurrences in the present outbreak are being reported in many countries. It is not yet known how this... (Review)
Review
While monkeypox was previously found in Africa, the bulk of occurrences in the present outbreak are being reported in many countries. It is not yet known how this outbreak began, and as the COVID-19 crisis begins to abate, numerous nations throughout the world are now contending with a novel outbreak. Monkeypox is a transmissible virus between animals and humans, belonging to the Orthopoxvirus genus of the Poxviridae family. In the 1970s, cases of monkeypox began increasing due to the cessation of vaccination against smallpox, which drew international attention. The virus was named monkeypox because it was first observed in macaque monkeys. It is thought to be transmitted by several different rodents and small mammals, though the origin of the virus is not known. Monkeypox, while occasionally transmitted from one human to another, can be disseminated through the inhalation of droplets or through contact with the skin lesions of an infected individual. Unfortunately, there is no definitive cure for monkeypox; however, supportive care can be offered to ameliorate its symptoms. In severe cases, medications like tecovirimat may be administered. However, there are no established guidelines for symptom management in monkeypox cases. In this article we have discussed about different aspects of monkeypox including viral structure, transmission, replication, clinical manifestations, vaccination, treatment and current prevalence in the world to understand it better and give insight to the future studies.
Topics: Animals; Humans; Monkeypox virus; Mpox (monkeypox); COVID-19; Disease Outbreaks; Africa; Mammals
PubMed: 36758824
DOI: 10.1016/j.micpath.2023.106027 -
EBioMedicine Jan 2023Human monkeypox is a viral zoonotic smallpox-like disease caused by the monkeypox virus (MPXV) and has become the greatest public health threat in the genus... (Review)
Review
Human monkeypox is a viral zoonotic smallpox-like disease caused by the monkeypox virus (MPXV) and has become the greatest public health threat in the genus Orthopoxvirus after smallpox was eradicated. The host immune response to MPXV plays an essential role in disease pathogenesis and clinical manifestations. MPXV infection leads to skin lesions with the genital area as the main feature in the current outbreak and triggers a strong immune response that results in sepsis, deep tissue abscess, severe respiratory disease, and injuries to multiple immune organs. Emerging evidence shows that the immunopathogenesis of MPXV infection is closely associated with impaired NK-cell function, lymphopenia, immune evasion, increased antibodies, increased blood monocytes and granulocytes, cytokine storm, inhibition of the host complement system, and antibody-dependent enhancement. In this overview, we discuss the immunopathology and immunopathogenesis of monkeypox to aid the development of novel immunotherapeutic strategies against monkeypox.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Smallpox; Immunity
PubMed: 36584594
DOI: 10.1016/j.ebiom.2022.104424 -
Clinical Microbiology and Infection :... Dec 2023Monkeypox virus (MPXV) is an emerging zoonotic virus that has had on-going public health impacts in endemic regions of Central and West Africa for over a half-century.... (Review)
Review
BACKGROUND
Monkeypox virus (MPXV) is an emerging zoonotic virus that has had on-going public health impacts in endemic regions of Central and West Africa for over a half-century. Historically, the MPXV clade endemic in regions of Central Africa is associated with higher morbidity and mortality as compared with the clade endemic in West Africa.
OBJECTIVES
Here, we review the virological characteristics of MPXV and discuss potential relationships between virulence factors and clade- (and subclade-) specific differences in virulence and transmission patterns.
SOURCES
Targeted search was conducted in PubMed using ((monkeypox virus) OR (Orthopoxvirus)) AND (zoonosis)) OR ((monkeypox) OR (human mpox).
CONTENT
Forty-seven references were considered that included three publicly available data reports and/or press releases, one book chapter, and 44 published manuscripts.
IMPLICATIONS
Although zoonosis has been historically linked to emergence events in humans, epidemiological analyses of more recent outbreaks have identified increasing frequencies of human-to-human transmission. Furthermore, viral transmission during the 2022 global human mpox outbreak, caused by a recently identified MPXV subclade, has relied exclusively on human-to-human contact with no known zoonotic link.
Topics: Humans; Monkeypox virus; Mpox (monkeypox); Virulence; Virulence Factors; Africa, Western
PubMed: 37507009
DOI: 10.1016/j.cmi.2023.07.011 -
Revista Espanola de Quimioterapia :... Dec 2022Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an... (Review)
Review
Infection caused by Monkeypox Virus (MPVX) has small rodents as its natural reservoir and both monkeys and humans are occasional hosts. The causative agent is an Orthopoxvirus (MPVX) that was isolated in monkeys in 1958 and proved capable of passing to humans in 1970. It remained contained in Africa, causing isolated episodes of infection, until 2003 when an outbreak occurred in the United States following importation of animals from that continent. Since then, anecdotal cases have continued to be reported outside Africa, usually very clearly linked to travelers to those countries, but in May 2022, a broad outbreak of this disease has begun, now affecting several continents, with the emergence of human cases of MPVX (H-MPVX) infection mainly among Men that have Sex with Men (MSM). The disease has an incubation time ranging from 5 to 15 days and is characterized by the presence of pustules, fever, malaise and headache. The presence of significant regional lymphadenopathy is a differential feature with episodes of classical smallpox. Proctitis and pharyngitis, with minimal skin lesions, may be another form of presentation. Diagnosis can be confirmed by PCR testing of lesions or by demonstration of MPVX in other body fluids or tissues, although in the appropriate epidemiologic setting the clinical picture is highly suggestive of the disease. Effective drug treatment has been developed as part of programs to protect against potential bioterrorist agents and smallpox vaccinees are known to have high protection against monkeypox. New vaccines are available, but neither the drugs nor the vaccines are yet freely available on the market. The prognosis of the disease appears, at least in adults in developed countries, to be good, with very low mortality figures and much less aggressive behavior than that described in classical smallpox. Isolation measures, essential for the control of the outbreak, have been published by the health authorities.
Topics: Male; Adult; Animals; Humans; United States; Mpox (monkeypox); Smallpox; Homosexuality, Male; Sexual and Gender Minorities; Monkeypox virus; Disease Outbreaks
PubMed: 35785957
DOI: 10.37201/req/059.2022