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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 -
Communications Medicine Feb 2024Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning...
BACKGROUND
Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity.
METHODS
We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice.
RESULTS
COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1.
CONCLUSIONS
These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.
PubMed: 38366141
DOI: 10.1038/s43856-024-00443-9 -
The American Journal of Tropical... Mar 2024Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is...
Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in the DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated Rt of 0.82 (95% CI: 0.79-0.85) and a rate of 132 (95% CI: 122-143) spillovers per year assuming a reporting rate of 25%. This estimate of Rt is larger than most previous estimates. One potential explanation for this result is that Rt could have increased in the DRC over time owing to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. Rt could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.
Topics: Animals; Humans; Mpox (monkeypox); Democratic Republic of the Congo; Monkeypox virus; Zoonoses; Disease Outbreaks
PubMed: 38320310
DOI: 10.4269/ajtmh.23-0215 -
Discovering conserved epitopes of Monkeypox: Novel immunoinformatic and machine learning approaches.Heliyon Feb 2024The Monkeypox virus, an Orthopoxvirus with zoonotic origins, has been responsible for a growing number of human infections reminiscent of smallpox since May 2022, as...
The Monkeypox virus, an Orthopoxvirus with zoonotic origins, has been responsible for a growing number of human infections reminiscent of smallpox since May 2022, as reported by the World Health Organization. As of now, there are no established medical treatments for managing Monkeypox infections. In this study, we used machine learning to select conserved epitopes. Proteins were determined using Reverse Vaccinology and Gene Ontology subcellular localization, and their epitopes were predicted. NextClade was used to calculate the number of mutations in each amino acid position using 2433 Monkeypox sequences. The Unsupervised Nearest Neighbor machine learning algorithm and ideal matrix [0 0] were used to calculate the conservancy score of epitopes. Six proteins were determined for epitope prediction. Finally, 47 MHC-I epitopes, 5 MHC-II epitopes, and 10 Linear B cell epitopes were discovered. Our method can select epitopes for vaccine design to prevent viruses with accelerated evolution and high mutation rate.
PubMed: 38318007
DOI: 10.1016/j.heliyon.2024.e24972 -
Vaccine Mar 2024The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic...
The Mpox (formerly named Monkeypox) virus is the etiological cause of a recent multi-country outbreak, with thousands of distinct cases detected outside the endemic areas of Africa as of December 2023. In this article, we analyze the sequences of full genomes of Mpox virus from Europe and compare them with all available Mpox sequences of historical relevance, annotated by year and geographic origin, as well as related Cowpox and Variola (smallpox) virus sequences. Our results show that the recent outbreak is most likely originating from the West African clade of Mpox, with >99 % sequence identity with sequences derived from historical and recent cases, dating from 1971 to 2017. We analyze specific mutations occurring in viral proteins between the current outbreak, previous Mpox and Cowpox sequences, and the historical Variola virus. Genome-wide sequence analysis of the recent outbreak and other Mpox/Cowpox/Variola viruses shows a very high conservation, with 97.9 % (protein-based) and 97.8 % (nucleotide-based) sequence identity. We identified significant correlation in human transcriptional responses as well, with a conserved immune pathway response induced in human cell cultures by the three families of Pox virus. The similarities identified between the major strains of Pox viruses, as well as within the Mpox clades, both at the genomic and transcriptomic levels, provide a molecular basis for the observed efficacy of Variola vaccines in other Poxviruses.
Topics: Animals; Humans; Smallpox; Cowpox; Mpox (monkeypox); DNA, Viral; Variola virus; Poxviridae; Monkeypox virus; Genomics; Disease Outbreaks; Gene Expression Profiling
PubMed: 38311533
DOI: 10.1016/j.vaccine.2023.12.086 -
Vaccine Feb 2024Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it...
Smallpox, caused by the variola virus belonging to the genus Orthopoxvirus, is an acute contagious disease that killed 300 million people in the 20th century. Since it was declared to be eradicated and the national immunization program against it was stopped, the variola virus has become a prospective bio-weapon. It is necessary to develop a safe vaccine that protects people from terrorism using this biological weapon and that can be administered to immunocompromised people. Our previous study reported on the development of an attenuated smallpox vaccine (KVAC103). This study evaluated cellular and humoral immune responses to various doses, frequencies, and routes of administration of the KVAC103 strain, compared to CJ-50300 vaccine, and its protective ability against the wild-type vaccinia virus Western Reserve (VACV-WR) strain was evaluated. The binding and neutralizing-antibody titers increased in a concentration-dependent manner in the second inoculation, which increased the neutralizing-antibody titer compared to those after the single injection. In contrast, the T-cell immune response (interferon-gamma positive cells) increased after the second inoculation compared to that of CJ-50300 after the first inoculation. Neutralizing-antibody titers and antigen-specific IgG levels were comparable in all groups administered KVAC103 intramuscularly, subcutaneously, and intradermally. In a protective immunity test using the VACV-WR strain, all mice vaccinated with CJ-50300 or KVAC103 showed 100% survival. KVAC103 could be a potent smallpox vaccine that efficiently induces humoral and cellular immune responses to protect mice against the VACV-WR strain.
Topics: Animals; Mice; Humans; Smallpox Vaccine; Smallpox; Variola virus; Vaccines, Attenuated; Prospective Studies; Vaccinia virus; Immunity, Cellular; Antigens, Viral; Antibodies, Viral; Mice, Inbred BALB C
PubMed: 38310019
DOI: 10.1016/j.vaccine.2024.01.064 -
Virologica Sinica Apr 2024The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic... (Review)
Review
The persistent epidemic of human mpox, caused by mpox virus (MPXV), raises concerns about the future spread of MPXV and other poxviruses. MPXV is a typical zoonotic virus which can infect human and cause smallpox-like symptoms. MPXV belongs to the Poxviridae family, which has a relatively broad host range from arthropods to vertebrates. Cross-species transmission of poxviruses among different hosts has been frequently reported and resulted in numerous epidemics. Poxviruses have a complex linear double-strand DNA genome that encodes hundreds of proteins. Genes related to the host range of poxvirus are called host range genes (HRGs). This review briefly introduces the taxonomy, phylogeny and hosts of poxviruses, and then comprehensively summarizes the current knowledge about the cross-species transmission of poxviruses. In particular, the HRGs of poxvirus are described and their impacts on viral host range are discussed in depth. We hope that this review will provide a comprehensive perspective about the current progress of researches on cross-species transmission and HRG variation of poxviruses, serving as a valuable reference for academic studies and disease control in the future.
Topics: Host Specificity; Animals; Humans; Poxviridae Infections; Poxviridae; Phylogeny; Genome, Viral
PubMed: 38272237
DOI: 10.1016/j.virs.2024.01.007 -
Emerging Infectious Diseases Feb 2024Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell...
Among persons born in China before 1980 and tested for vaccinia virus Tiantan strain (VVT), 28.7% (137/478) had neutralizing antibodies, 71.4% (25/35) had memory B-cell responses, and 65.7% (23/35) had memory T-cell responses to VVT. Because of cross-immunity between the viruses, these findings can help guide mpox vaccination strategies in China.
Topics: Humans; Mpox (monkeypox); Smallpox; Vaccination; Antibodies, Neutralizing; China; Vaccinia virus
PubMed: 38270156
DOI: 10.3201/eid3002.230542 -
Frontiers in Public Health 2023Over the past two centuries, vaccines have been critical for the prevention of infectious diseases and are considered milestones in the medical and public health... (Review)
Review
Over the past two centuries, vaccines have been critical for the prevention of infectious diseases and are considered milestones in the medical and public health history. The World Health Organization estimates that vaccination currently prevents approximately 3.5-5 million deaths annually, attributed to diseases such as diphtheria, tetanus, pertussis, influenza, and measles. Vaccination has been instrumental in eradicating important pathogens, including the smallpox virus and wild poliovirus types 2 and 3. This narrative review offers a detailed journey through the history and advancements in vaccinology, tailored for healthcare workers. It traces pivotal milestones, beginning with the variolation practices in the early 17th century, the development of the first smallpox vaccine, and the continuous evolution and innovation in vaccine development up to the present day. We also briefly review immunological principles underlying vaccination, as well as the main vaccine types, with a special mention of the recently introduced mRNA vaccine technology. Additionally, we discuss the broad benefits of vaccines, including their role in reducing morbidity and mortality, and in fostering socioeconomic development in communities. Finally, we address the issue of vaccine hesitancy and discuss effective strategies to promote vaccine acceptance. Research, collaboration, and the widespread acceptance and use of vaccines are imperative for the continued success of vaccination programs in controlling and ultimately eradicating infectious diseases.
Topics: Humans; Vaccination; Immunization; Antigens, Viral; Influenza Vaccines; Communicable Diseases
PubMed: 38264254
DOI: 10.3389/fpubh.2023.1326154 -
Mikrobiyoloji Bulteni Jan 2024Monkeypox virus (MPXV) infection is a zoonotic disease characterized by smallpox-like rashes. It is endemic in Central and West Africa. The World Health Organization...
Monkeypox virus (MPXV) infection is a zoonotic disease characterized by smallpox-like rashes. It is endemic in Central and West Africa. The World Health Organization (WHO) declared the disease as an epidemic due to a significant increase in the number of reported cases, starting from Europe and spreading to other regions, particularly in certain areas, in May 2022. On July 23, 2022, it was recognized as a public health problem of international importance. Our country has also been affected by this epidemic, and the official number of reported cases is twelve. In this case report, an adolescent case diagnosed with MPXV infection was presented. A 17-year-old male patient admitted with the complaints of sores around the mouth and genital area, fever and headache. The patient had a history of sexual contact with three different males in the last six months. Honey-colored crusted papules and plaques were observed in the perioral area, as well as crusted papules on the penile and gluteal areas. Ulcerative sores were present in the oral cavity. Laboratory tests for sexually transmitted diseases confirmed the patient's HIV-positive status and MPXV infection through PCR (polymerase chain reaction) testing. Antiviral treatment for human immunodeficiency virus (HIV) was initiated after the HIV RNA level resulted in 263000 copies/mL. Additionally, a glycopeptide was added to the treatment regimen when methicillin-resistant Staphylococcus aureus growth was detected in the swab culture taken from the wounds on the patient's face. No specific treatment was administered for MPXV due to the patient's uncomplicated clinical course and overall well-being. This case report aims to raise awareness about monkeypox disease in children by highlighting the clinical findings and potential risk factors.
Topics: Child; Male; Animals; Humans; Adolescent; Mpox (monkeypox); Methicillin-Resistant Staphylococcus aureus; Zoonoses; Europe; HIV Infections
PubMed: 38263944
DOI: 10.5578/mb.20249909