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Nature Communications May 2024The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was... (Meta-Analysis)
Meta-Analysis
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
Topics: Animals; Humans; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay; Smallpox Vaccine; Vaccination; Vaccine Efficacy; Vaccinia; Monkeypox virus
PubMed: 38719852
DOI: 10.1038/s41467-024-48180-w -
Microbiology Spectrum Jun 2024Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical...
UNLABELLED
Smallpox is a highly contagious human disease caused by the variola virus. Although the disease was eliminated in 1979 due to its highly contagious nature and historical pathogenicity, with a mortality rate of up to 30%, this virus is an important candidate for biological weapons. Currently, vaccines are the critical measures to prevent this virus infection and spread. In this study, we designed a peptide vaccine using immunoinformatics tools, which have the potential to activate human immunity against variola virus infection efficiently. The design of peptides derives from vaccine-candidate proteins showing protective potential in vaccinia WR strains. Potential non-toxic and nonallergenic T-cell and B-cell binding and cytokine-inducing epitopes were then screened through a priority prediction using special linkers to connect B-cell epitopes and T-cell epitopes, and an appropriate adjuvant was added to the vaccine construction to enhance the immunogenicity of the peptide vaccine. The 3D structure display, docking, and free energy calculation analysis indicate that the binding affinity between the vaccine peptide and Toll-like receptor 3 is high, and the vaccine receptor complex is highly stable. Notably, the vaccine we designed is obtained from the protective protein of the vaccinia and combined with preventive measures to avoid side effects. This vaccine is highly likely to produce an effective and safe immune response against the variola virus infection in the body.
IMPORTANCE
In this work, we designed a vaccine with a cluster of multiple T-cell/B-cell epitopes, which should be effective in inducing systematic immune responses against variola virus infection. Besides, this work also provides a reference in vaccine design for preventing monkeypox virus infection, which is currently prevalent.
Topics: Epitopes, B-Lymphocyte; Epitopes, T-Lymphocyte; Vaccines, Subunit; Humans; Smallpox Vaccine; Computational Biology; Variola virus; Smallpox; T-Lymphocytes; B-Lymphocytes; Molecular Docking Simulation; Peptides; Immunoinformatics
PubMed: 38700327
DOI: 10.1128/spectrum.00465-24 -
Indian Journal of Pharmacology Mar 2024The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox... (Review)
Review
The virus known as monkeypox is the source of the zoonotic disease monkeypox, which was historically widespread in Central Africa and West Africa. The cases of monkeypox in humans are uncommon outside of West and Central Africa, but copious nonendemic nations outside of Africa have recently confirmed cases. People when interact with diseased animals, then, they may inadvertently contact monkeypox. There are two drugs in the market: brincidofovir and tecovirimat and both of these drugs are permitted for the cure of monkeypox by the US Food and Drug Administration. The present review summarizes the various parameters of monkeypox in context with transmission, signs and symptoms, histopathological and etiological changes, and possible treatment. Monkeypox is clinically similar to that of smallpox infection but epidemiologically, these two are different, the present study also signifies the main differences and similarities of monkeypox to that of other infectious diseases. As it is an emerging disease, it is important to know about the various factors related to monkeypox so as to control it on a very early stage of transmission.
Topics: Mpox (monkeypox); Humans; Animals; Antiviral Agents; Communicable Diseases, Emerging; Cytosine; Monkeypox virus; Isoindoles; Organothiophosphorus Compounds; Organophosphonates; Benzamides; Phthalimides
PubMed: 38687317
DOI: 10.4103/ijp.ijp_156_23 -
Viruses Apr 2024To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific...
AIMS
To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory.
METHODS
Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry.
RESULTS
None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals.
CONCLUSIONS
ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.
Topics: Humans; Antibodies, Viral; Smallpox Vaccine; B-Lymphocytes; Antibodies, Neutralizing; Cross Reactions; Vaccinia virus; Middle Aged; Immunologic Memory; Neutralization Tests; Smallpox; Animals; Male; T-Lymphocytes; Female; Enzyme-Linked Immunosorbent Assay; Orthopoxvirus; Vaccination; Chlorocebus aethiops; Adult; Lymphocyte Activation; Vero Cells
PubMed: 38675961
DOI: 10.3390/v16040620 -
International Journal of Paleopathology Jun 2024This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in...
OBJECTIVE
This project seeks to create a differential diagnosis for lesions found on the skeletal remains of two children as a means to explore the presence of viral disease in 16th- century Peru.
MATERIALS
Extremely well-preserved human remains of two children who died between the ages of 1-2 years old, recovered from the circum-contact (∼1540 CE) cemetery in Huanchaco, Peru.
METHODS
Macroscopic and radiographic analysis.
RESULTS
Both individuals present with cortical thickening, symmetrical destructive lesions, metaphyseal expansion, perforations, exposure of the medullary cavity, resorption of metaphyseal ends and necrosis of the long bones, and deposited reactive new bone. These features are consistent with osteomyelitis variolosa and bacterial osteomyelitis.
CONCLUSIONS
Three features of Individuals IG-124 and IG-493 suggest a highly consistent diagnosis of osteomyelitis variolosa: multiple skeletal lesions, the historical context of the area, and the high mortality rate of non-adults in the circum-contact cemetery.
SIGNIFICANCE
Although viral infections are ubiquitous and well documented historically, their etiologies are often difficult to determine in archaeological populations. Orthopoxvirus variola (smallpox) is one of the many viruses whose archaeological impact is still under explored in skeletal remains.
LIMITATIONS
The absence of smallpox in other children from the Huanchaco cemetery creates difficulty in ascertaining true prevalence rates or information on potential outbreaks.
SUGGESTIONS FOR FURTHER RESEARCH
Further research analyzing aDNA from calculus and/or residues using a DIP-GC-MS method might create a better understanding of how smallpox spread through the region.
Topics: Humans; Smallpox; Peru; History, 16th Century; Infant; Child, Preschool; Male; Osteomyelitis; Paleopathology; Female; Cemeteries
PubMed: 38653101
DOI: 10.1016/j.ijpp.2024.04.002 -
Journal of Clinical Microbiology May 2024The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use...
UNLABELLED
The mpox outbreak, caused by monkeypox virus (MPXV), accelerated the development of molecular diagnostics. In this study, we detail the evaluation of the Research Use Only (RUO) NeuMoDx MPXV assay by multiple European and US sites. The assay was designed and developed by Qiagen for the NeuMoDx Molecular Systems. Primers and probes were tested for specificity and inclusivity . The analytical sensitivity of the assay was determined by testing dilutions of synthetic and genomic MPXV DNA. A total of 296 clinical samples were tested by three sites; the Johns Hopkins University (US), UZ Gent (Belgium, Europe), and Hospital Universitario San Cecilio (Spain, Europe). The analytical sensitivity of the assay was 50 copies/mL for both clades I and II. The assay showed 100% identity for 80 clade I and 99.98% identity for 5,162 clade II genomes. Clade II primers and probes showed 100% specificity; however, identity of at least one of the two sets of clade I primers and probes with variola, cowpox, camelpox, and vaccinia viruses was noticed. The clinical validation showed sensitivity of 99.21% [95% confidence interval (CI): 95.66-99.98%] and specificity of 96.64% (95% CI: 91.62-99.08%) for lesion swab samples. The NeuMoDx MPXV Test shows acceptable analytical and clinical performance. The assay improves the laboratory's workflow as it consolidates nucleic acid extraction, PCR, data analysis, and interpretation and can be interfaced. The Test Strip can differentiate clades I and II, which has important laboratory safety implications.
IMPORTANCE
In this manuscript, we provide detailed analysis and clinical evaluation of the assay using a large cohort of clinical samples across three academic centers in Europe and the United States. Because the assay differentiates MPXV clades I and II, this manuscript is timely due to the current need to rule out the regulated clade I by diagnostic clinical laboratories. In December 2023, and due to first report of cases of sexually transmitted clade I infections in the Democratic Republic of the Congo, when generic assays that do not differentiate the clades are used, samples are considered regulated. The assay meets the need of full automation and has a marked positive impact on the laboratory workflow.
Topics: Humans; Sensitivity and Specificity; Monkeypox virus; Real-Time Polymerase Chain Reaction; Mpox (monkeypox); Molecular Diagnostic Techniques; Europe; United States; Automation, Laboratory; DNA Primers; Belgium
PubMed: 38639489
DOI: 10.1128/jcm.00028-24 -
Frontiers in Immunology 2024Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and...
Whole genome sequencing of recombinant viruses obtained from co-infection and superinfection of Vero cells with modified vaccinia virus ankara vectored influenza vaccine and a naturally occurring cowpox virus.
Modified vaccinia virus Ankara (MVA) has been widely tested in clinical trials as recombinant vector vaccine against infectious diseases and cancers in humans and animals. However, one biosafety concern about the use of MVA vectored vaccine is the potential for MVA to recombine with naturally occurring orthopoxviruses in cells and hosts in which it multiplies poorly and, therefore, producing viruses with mosaic genomes with altered genetic and phenotypic properties. We previously conducted co-infection and superinfection experiments with MVA vectored influenza vaccine (MVA-HANP) and a feline Cowpox virus (CPXV-No-F1) in Vero cells (that were semi-permissive to MVA infection) and showed that recombination occurred in both co-infected and superinfected cells. In this study, we selected the putative recombinant viruses and performed genomic characterization of these viruses. Some putative recombinant viruses displayed plaque morphology distinct of that of the parental viruses. Our analysis demonstrated that they had mosaic genomes of different lengths. The recombinant viruses, with a genome more similar to MVA-HANP (>50%), rescued deleted and/or fragmented genes in MVA and gained new host ranges genes. Our analysis also revealed that some MVA-HANP contained a partially deleted transgene expression cassette and one recombinant virus contained part of the transgene expression cassette similar to that incomplete MVA-HANP. The recombination in co-infected and superinfected Vero cells resulted in recombinant viruses with unpredictable biological and genetic properties as well as recovery of delete/fragmented genes in MVA and transfer of the transgene into replication competent CPXV. These results are relevant to hazard characterization and risk assessment of MVA vectored biologicals.
Topics: Chlorocebus aethiops; Animals; Cats; Humans; Influenza Vaccines; Cowpox virus; Vero Cells; Coinfection; Superinfection; Vaccinia virus; Vaccines, Synthetic; Whole Genome Sequencing
PubMed: 38633245
DOI: 10.3389/fimmu.2024.1277447 -
Proceedings (Baylor University. Medical... 2024Mpox is a double-stranded DNA virus of the Orthopoxvirus genus related to smallpox virus endemic to Africa with more than 16,000 cases reported in nonendemic countries...
Mpox is a double-stranded DNA virus of the Orthopoxvirus genus related to smallpox virus endemic to Africa with more than 16,000 cases reported in nonendemic countries in 2022. Classically associated with adult men who have sex with men (MSM), Mpox was once labeled a public health emergency by the World Health Organization as concerning to the general population. Supraglottitis is a rare complication of Mpox that is underreported in the literature and presents a potential airway emergency. Prompt identification is necessary for preventing airway decompensation.
PubMed: 38628346
DOI: 10.1080/08998280.2024.2314408 -
Nature Communications Apr 2024The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity...
The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation of the vaccination campaign against the virus. Consequently, immunity against smallpox and related orthopoxviruses like Monkeypox virus gradually declines, highlighting the need for efficient countermeasures not only for the prevention, but also for the treatment of already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 and EV42, targeting the two infectious forms of the virus, were selected for in vivo evaluation, based on their in vitro neutralization potency. A single dose of either MV33 or EV42 administered three days post-infection (dpi) to BALB/c female mice provides full protection against lethal ectromelia virus challenge. Importantly, a combination of both mAbs confers full protection even when provided five dpi. Whole-body bioimaging and viral load analysis reveal that combination of the two mAbs allows for faster and more efficient clearance of the virus from target organs compared to either MV33 or EV42 separately. The combined mAbs treatment further confers post-exposure protection against the currently circulating Monkeypox virus in Cast/EiJ female mice, highlighting their therapeutic potential against other orthopoxviruses.
Topics: Humans; Female; Animals; Mice; Smallpox; Antibodies, Monoclonal; Poxviridae Infections; Vaccinia; Vaccinia virus; Orthopoxvirus; Antibodies, Viral
PubMed: 38627363
DOI: 10.1038/s41467-024-47328-y -
Journal of Infection and Public Health Jun 2024After the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV...
BACKGROUND
After the eradication of smallpox, there have been no specific public health measures for any Orthopoxviruses (OPXVs). Therefore, it is necessary to countermeasure OPXV infections after Mpox (formerly monkeypox) occurrences, such as the latest global outbreak in 2022-2023. This study aimed to provide crucial insights for the development of effective public health policy making against mpox in populations residing in regions where the virus is not prevalent.
METHODS
This study used enzyme-linked immunosorbent assays (ELISA) to examine smallpox and mpox antibodies in Koreans with three different age groups. We analyzed 56 sera obtained from a tertiary care hospital in South Korea between September 2022 and April 2023. Plasma levels of antibodies against the viral proteins of smallpox (variola cytokine response-modifying protein B) and MPXV (A29) were measured using enzyme-linked immunosorbent assays.
RESULTS
Plasma samples from participants in their early 40 s and older exhibited higher reactivity to viral antigens than those from younger participants. Furthermore, there was a strong positive correlation in antibody positivity for the two different viruses across the sera.
CONCLUSIONS
The presence of low antibody levels in participants ˂40 years may hinder their ability to defend against OPXV. Therefore, it is imperative to implement effective public health measures to mitigate the transmission of OPXV within the community. These findings serve as fundamental information for devising strategies to combat mpox efficiently, particularly in regions where the virus is not prevalent.
Topics: Humans; Adult; Antibodies, Viral; Republic of Korea; Male; Middle Aged; Young Adult; Enzyme-Linked Immunosorbent Assay; Female; Orthopoxvirus; Age Factors; Public Health; Aged; Adolescent; Antibody Formation; Smallpox; Poxviridae Infections; Mpox (monkeypox)
PubMed: 38608456
DOI: 10.1016/j.jiph.2024.04.002