Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) as a smallpox and mpox vaccine has been approved in its liquid-frozen (LF) formulation in the US, Canada, and EU. A freeze-dried (FD) formulation may offer additional benefits, such as a longer shelf life and reduced dependence on cold chain storage and transport. In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety, and reactogenicity. Non-inferiority of the immune response was assessed by the 95% CI of the geometric mean ratios. Both formulations induced robust vaccinia-specific humoral and cellular immune responses. At peak humoral responses (Week 6), geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At peak cellular responses (Week 2), geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly more local reactions in the FD group. No vaccine-related serious adverse events (SAEs) or vaccine-related AE of special interest were reported. The FD formulation of MVA-BN was shown to be equivalent to MVA-BN LF.

In the recent mpox outbreak, people living with HIV (PLWH) were at high risk both for contracting infection and for suffering a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PLWH) or smallpox vaccination (n = 17; all PLWH) in a cohort of men who have sex with men. All PLWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. 11/17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both two-dose MVA-vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination mediated cross-reactivity to other orthopox viruses, and the long-lasting durability of childhood smallpox vaccination mediated immune responses including in PLWH.

The monkeypox virus (MPXV) outbreak in 2022 has renewed interest in the detection of antibodies against orthopox viruses (OPXV) and MPXV, as serological methods can aid diagnostics and are key to epidemiological studies. Here three complementary serological methods are described with different strengths to aid the development and evaluation of in-house assays: An immunofluorescence assay (IFA) for specific detection of IgG and IgM, an enzyme-linked immunosorbent assay for higher sample throughput to aid epidemiological studies and a neutralization test to detect virus neutralizing antibodies. As implementation of MPXV-specific diagnostics is often hampered by the requirement for a dedicated biosafety level 3 laboratory (BSL-3), the focus of this study is on biosafety aspects to facilitate safe testing also under BSL-2 conditions. To this aim, it was analyzed whether OPXV, which can be handled under BSL-2 conditions, could be used as less virulent alternatives to MPXV. Furthermore, an inactivation method was established to remove up to five log-steps of infectious virus particles from viraemic sera without compromising antibody detection. The results show that immunological cross-reactivity between OPXV provides an opportunity for the interchangeable usage of different OPXV species in serological assays, enabling MPXV serology outside of BSL-3 facilities.

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Monkeypox is a rare zoonotic DNA with lineage from the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. With a previous history of controlled and contained occasional outbreaks of the virus, currently, a widely erupted outbreak of monkeypox with progressively rising numbers has been reported since May 2022 in multiple countries of the western hemisphere that are not historically endemic for this infection, particularly the United Kingdom and European Union countries. We have written a comprehensive review article to help clinicians better understand the disease. The global cessation of smallpox vaccination has been hypothesized to cause the rise in monkeypox infections in recent years. Monkeypox, like any other viral infection, commences with prodromal symptoms; a maculopapular rash with centrifugal distribution usually follows. Polymerase chain reaction (PCR) confirms the diagnosis. Transmission in humans is possible through infected animals or humans. In the ongoing 2022 outbreak, the monkeypox virus has been undergoing novel mutations at an alarming rate. Treatment options for monkeypox are an area that still requires extensive research, and the utility of certain antiviral medications in treating monkeypox infection is currently being explored but is still controversial and debatable.

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance.

Monkeypox 2022, a zoonotic virus similar to smallpox, presented as a rapidly escalating human outbreak with community transmission outside endemic regions of Africa. In just over one month of detection, confirmed cases escalated to over 3300, with reports of patients in at least 43 non-African nations. Mechanisms of transmission in animals and the reservoir host remain uncertain; spread from humans to wild or domestic animals risks the creation of new endemic zones. While initial cases were reported in men who have sex with men (MSM), monkeypox is not considered a sexually transmitted infection. Anyone with close contact with an infected person, aerosolized infectious material (e.g., from shaken bedsheets), or contact with fomites or infected animals is at risk. In humans, monkeypox typically presents with a non-specific prodromal phase followed by a classic rash with an incubation period of 5-21 days (usually 6-13 days). The prodrome may be subclinical, and the monkeypox virus may be transmissible from person-to-person before observed symptom onset. Most clinicians are unfamiliar with monkeypox. Information is rapidly evolving, producing an urgent need for immediate access to clear, concise, fact-based, and actionable information for frontline healthcare workers in prehospital, emergency departments/hospitals, and acute care/sexual transmitted infection clinics. This paper provides a novel Identify-Isolate-Inform (3I) Tool for the early detection and management of patients under investigation for monkeypox 2022. Patients are identified as potentially exposed or infected after an initial assessment of risk factors and signs/symptoms. Management of exposed patients includes consideration of quarantine and post-exposure prophylaxis with a smallpox vaccine. For infectious patients, providers must immediately don personal protective equipment and isolate patients. Healthcare workers must report suspected and confirmed cases in humans or animals to public health authorities. This innovative 3I Tool will assist emergency, primary care, and prehospital clinicians in effectively managing persons with suspected or confirmed monkeypox.

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The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus.
The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity.
We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care.
A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively.
Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients.