Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have ...considerable side effects.
To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio.
A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 95% confidence interval {CI}, 1.56 to 2.40). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm
in the MVA group and 76.0 mm
in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P<0.001).
No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).
We report the autopsy pathology findings of a 21-week stillborn fetus with congenital mpox syndrome that occurred in the Democratic Republic of the Congo in 2008. The fetus acquired mpox from the ...mother after intrauterine transplacental monkeypox virus transmission. We confirmed monkeypox virus infection in the mother, fetus, and placenta by using a monkeypox virus-specific quantitative PCR. Subtyping of the virus was not performed, but the mother and fetus were almost certainly infected with the clade I variant that was endemic in the Democratic Republic of the Congo at the time. Risk for intrauterine infection appears to differ between virus clades, but clinicians should be aware of potential for intrauterine monkeypox virus transmission among pregnant persons during ongoing and future mpox outbreaks.
In African countries where mpox (monkeypox) is endemic, infection is caused by two genetically related clades-Clade I (formerly Congo Basin), and Clade IIa (formerly West Africa), both of which are ...potentially life-threatening infections. Prior to the 2022-2023 global outbreak, mpox infections among pregnant women caused by Clade I were reported to have a 75% perinatal case fatality rate in the Democratic Republic of Congo, including the only documented case of placental infection and stillbirth from the Congenital Mpox Syndrome, and the Clade IIa mpox infection was associated with stillbirths in Nigeria. The 2022-2023 global mpox outbreak, caused by a genetically distinct strain, Clade IIb, has focused attention on the effects of mpox on pregnant women and fetal outcomes. There have been at least 58 cases of mpox infection occurring in pregnant women during the 2022-2023 outbreak. No confirmed cases of adverse perinatal outcome, including stillbirth, have been reported. The absence of perinatal morbidity and mortality from Clade IIb corresponds to the overall case fatality rate among non-pregnant women of <0.1%, as this clade has been demonstrated to produce a less-severe disease than the mpox Clade I or IIa variants. Thus, there are apparently important differences between mpox clades affecting pregnant women and perinatal outcomes.
Monkeypox and pregnancy: correspondence Schwartz, David A.; Pittman, Phillip R.
American journal of obstetrics and gynecology,
03/2023, Letnik:
228, Številka:
3
Journal Article
A Modified Vaccine against Smallpox. Reply Pittman, Phillip R; Weidenthaler, Heinz; Chaplin, Paul
The New England journal of medicine,
03/2020, Letnik:
382, Številka:
13
Journal Article
* Context.--Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox) virus is now the ...most pathogenic member of the Orthopoxvirus genus infecting humans. The 2022 global mpox outbreak has focused attention on its potential effects during pregnancy. Objective.--To understand the comparative effects of different poxvirus infections on pregnancy, including mpox virus, variola virus, vaccinia virus, and cowpox virus. The impact on the pregnant individual, fetus, and placenta will be examined, with particular attention to the occurrence of intrauterine vertical transmission and congenital infection. Data Sources.--The data are obtained from the authors' cases and from various published sources, including early historical information and contemporary publications. Conclusions.--Smallpox caused maternal and perinatal death, with numerous cases reported of intrauterine transmission. In endemic African countries, mpox has also affected pregnant individuals, with up to a 75% perinatal case fatality rate. Since the start of the 2022 mpox outbreak, increasing numbers of pregnant women have been infected with the virus. A detailed description is given of the congenital mpox syndrome in a stillborn fetus, resulting from maternal-fetal transmission and placental infection, and the potential mechanisms of intrauterine infection are discussed. Other poxviruses, notably vaccinia virus and, in 1 case, cowpox virus, can also cause perinatal infection. Based on the historical evidence of poxvirus infections, mpox remains a threat to the pregnant population, and it can be expected that additional cases will occur in the future. (Arch Pathol Lab Med. 2023;147:746-757; doi: 10.5858/ arpa.2022-0520-SA)
We describe the results of a prospective observational study of the clinical natural history of human monkeypox (mpox) virus (MPXV) infections at the remote L'Hopital General de Reference de Kole ...(Kole hospital), the rainforest of the Congo River basin of the Democratic Republic of the Congo (DRC) from March 2007 until August 2011. The research was conducted jointly by the Institute National de Recherche Biomedical (INRB) and the US Army Medical Research Institute of Infectious Diseases (USAMRIID). The Kole hospital was one of the two previous WHO Mpox study sites (1981-1986). The hospital is staffed by a Spanish Order of Catholic Nuns from La Congregation Des Soeurs Missionnaires Du Christ Jesus including two Spanish physicians, who were members of the Order as well, were part of the WHO study on human mpox. Of 244 patients admitted with a clinical diagnosis of MPXV infection, 216 were positive in both the Pan-Orthopox and MPXV specific PCR. The cardinal observations of these 216 patients are summarized in this report. There were three deaths (3/216) among these hospitalized patients; fetal death occurred in 3 of 4 patients who were pregnant at admission, with the placenta of one fetus demonstrating prominent MPXV infection of the chorionic villi. The most common complaints were rash (96.8%), malaise (85.2%), sore throat (78.2%), and lymphadenopathy/adenopathy (57.4%). The most common physical exam findings were mpox rash (99.5%) and lymphadenopathy (98.6%). The single patient without the classic mpox rash had been previously vaccinated against smallpox. Age group of less than 5 years had the highest lesion count. Primary household cases tended to have higher lesion counts than secondary or later same household cases. Of the 216 patients, 200 were tested for IgM & IgG antibodies (Abs) to Orthopoxviruses. All 200 patients had anti-orthopoxvirus IgG Abs; whereas 189/200 were positive for IgM. Patients with hypoalbuminemia had a high risk of severe disease. Patients with fatal disease had higher maximum geometric mean values than survivors for the following variables, respectively: viral DNA in blood (DNAemia); maximum lesion count; day of admission mean AST and ALT.
Mpox Virus in Pregnancy, the Placenta, and Newborn Schwartz, David A; Ha, Sandy; Dashraath, Pradip ...
Archives of pathology & laboratory medicine (1976),
07/2023, Letnik:
147, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox) virus is now the most ...pathogenic member of the Orthopoxvirus genus infecting humans. The 2022 global mpox outbreak has focused attention on its potential effects during pregnancy.
To understand the comparative effects of different poxvirus infections on pregnancy, including mpox virus, variola virus, vaccinia virus, and cowpox virus. The impact on the pregnant individual, fetus, and placenta will be examined, with particular attention to the occurrence of intrauterine vertical transmission and congenital infection.
The data are obtained from the authors' cases and from various published sources, including early historical information and contemporary publications.
Smallpox caused maternal and perinatal death, with numerous cases reported of intrauterine transmission. In endemic African countries, mpox has also affected pregnant individuals, with up to a 75% perinatal case fatality rate. Since the start of the 2022 mpox outbreak, increasing numbers of pregnant women have been infected with the virus. A detailed description is given of the congenital mpox syndrome in a stillborn fetus, resulting from maternal-fetal transmission and placental infection, and the potential mechanisms of intrauterine infection are discussed. Other poxviruses, notably vaccinia virus and, in 1 case, cowpox virus, can also cause perinatal infection. Based on the historical evidence of poxvirus infections, mpox remains a threat to the pregnant population, and it can be expected that additional cases will occur in the future.
A Modified Vaccine against Smallpox Engler, Renata; Cooper, Leslie T
The New England journal of medicine,
03/2020, Letnik:
382, Številka:
13
Journal Article
Rift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here, we report the isolation of a panel of monoclonal antibodies (mAbs) ...from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins. The Gn-specific mAbs and two mAbs that do not recognize either monomeric Gc or Gn alone but recognized the hetero-oligomer glycoprotein complex (Gc+Gn) when Gc and Gn were coexpressed exhibited potent neutralizing activities in vitro, while Gc-specific mAbs exhibited relatively lower neutralizing capacity. The two Gc+Gn-specific mAbs and the Gn domain A-specific mAbs inhibited RVFV fusion to cells, suggesting that mAbs can inhibit the exposure of the fusion loop in Gc, a class II fusion protein, and thus prevent fusion by an indirect mechanism without direct fusion loop contact. Competition-binding analysis with coexpressed Gc/Gn and mutagenesis library screening indicated that these mAbs recognize four major antigenic sites, with two sites of vulnerability for neutralization on Gn. In experimental models of infection in mice, representative mAbs recognizing three of the antigenic sites reduced morbidity and mortality when used at a low dose in both prophylactic and therapeutic settings. This study identifies multiple candidate mAbs that may be suitable for use in humans against RVFV infection and highlights fusion inhibition against bunyaviruses as a potential contributor to potent antibody-mediated neutralization.
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