The #pathogenicity and multi-organ proteomic profiles of #Mpox virus #infection in SIVmac239-infected rhesus #macaques

 

Abstract

Mpox poses a heightened risk of severe disease and mortality among individuals with HIV, yet the molecular mechanisms and immunopathology underlying multi-organ damage caused by the mpox virus (MPXV), particularly in the context of HIV co-infection, remain poorly understood. Here, we observe increased MPXV replication, more extensive skin lesions, and impaired humoral and cellular immune responses in SIV-MPXV co-infected rhesus macaques compared to those infected with MPXV alone. Multi-organ proteomic and phosphoproteomic analyses reveals upregulation of proteins involved in immune and inflammatory pathways in skin lesions and across multiple organs, especially in immune-related tissues. Abnormal activation of DNA replication and cell cycle signaling pathways, which may contribute to enhanced viral replication, is evident in both MPXV and SIV-MPXV co-infected groups. CDK4/6 may present a potential therapeutic target to suppress MPXV replication. These comprehensive proteomic datasets offer valuable insights into the pathogenesis of MPXV in the context of SIV co-infection and support ongoing efforts to mitigate the impact of mpox.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-62919-z

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

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A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments: M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic, expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries. The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat.1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts, including vertical transmissions, neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential.5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in extra-Amazonian Brazil, highlighting a potential synergistic mechanism of CNS invasion facilitated by HIV-induced immune dysregulation.

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Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00352-4/fulltext?rss=yes

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Safety and #effectiveness of MVA-BN #vaccination against #mpox in at-risk individuals in #Germany (SEMVAc and TEMVAc): a combined prospective and retrospective cohort study

Summary

Background

More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern. The third-generation smallpox vaccine modified vaccinia Ankara–Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox.

Methods

We did a prospective, multicentre, observational study, enrolling men who have sex with men and transgender people aged 18 years or older with changing sexual partners in Germany (Safety and Effectiveness of MVA-BN Vaccination Against MPXV Infection [SEMVAc]) between July 7, 2022, and Dec 31, 2023, evaluating safety and reactogenicity of one and two doses of subcutaneous MVA-BN. Vaccine effectiveness was estimated using risk ratios from the Kaplan–Meier estimator in an emulated retrospective target trial (Emulated Target Trial for Effectiveness of MVA-BN Vaccination Against mpox Infection in At-risk Individuals [TEMVAc]) from 3027 vaccinated individuals matched (1:1) to 3027 unvaccinated controls. SEMVAc and TEMVAc were registered in the HMA-EMA Catalogue, EUPAS50093, and the German Clinical Trials Register, DRKS00029638, and are complete.

Findings

6459 individuals were prospectively enrolled in SEMVAc. Adverse reactions were infrequent (first dose: 0·35% [95% CI 0·20–0·60] and second dose: 0·14% [0·06–0·33]). Local reactions were more frequent after the first dose (70·2% [95% CI 68·5–71·8]) compared with the second dose (56·8% [54·6–59]), as were systemic reactions (first dose, 22·3% [95% CI 20·9–23·9]; second dose, 17·6% [15·9–19·4]). In TEMVAc, 16 mpox cases were reported in vaccinated individuals versus 32 cases in matched unvaccinated individuals (median follow-up 55 days [IQR 23–89]). Effectiveness by 14 days or later after one dose was 57·8% (95% CI 11·8 to 83·0) overall, 84·1% (42·0 to 100) in people without HIV, but 34·9% (–72·8 to 79·0) in people living with HIV. Breakthrough infections were associated with reduced symptoms, compared with infections in unvaccinated individuals.

Interpretation

MVA-BN vaccination was safe and well tolerated. One dose of MVA-BN offered protection against mpox but effectiveness was reduced in people living with HIV. Although randomised controlled trials remain the preferred approach for assessing vaccine efficacy, combining prospective and retrospective study designs can be valuable during dynamic public health emergencies.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00018-0/fulltext?rss=yes

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