Mpox and related poxviruses: A literature review of evolution, pathophysiology, and clinical manifestations

Abstract

The recently re-emerged mpox (monkeypox) virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide. Numerous studies have contributed to our understanding of its evolution, pathophysiology, and clinical manifestations. The current outbreak of the mpox virus depicts its novel route of transmission as a new variant. However, the exact reason for its transition from an epidemic to a pandemic remains unclear. Furthermore, other poxviruses such as vaccinia virus, variola virus, and cowpox virus, also belong to the same genus, Orthopoxvirus. In the present review, our objective was to summarize the evidence on evolution, pathophysiology, and clinical manifestations of mpox virus and its related poxviruses. The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses. In addition, the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities. While they exhibit differences in virulence, studying these genetic relationships is crucial for understanding their biology, pathogenicity, and the development of effective vaccines and antiviral therapeutics to curb mpox disease.

Keywords

Evolution / Mpox / Orthopoxviruses / Pathophysiology / Poxviruses / Transmission

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The authors received no extramural funding for the study.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors' contributions

PB and RM conceived the idea of the manuscript and wrote and edited the manuscript. SS wrote a part and edited the manuscript. All authors have read and approved the manuscript submitted to the journal.

References

[1] Multi-country monkeypox outbreak in non-endemic countries: Update. [Online] Available from: www.who.int/emergencies/disease-outbreak-news/item/2022-DON388 [Accessed on 10th Feb 2024].

[2] Mpox (monkeypox), 18 April 2023. [Online] Available from: www.who.int/news-room/fact-sheets/detail/monkeypox#:~:text=The%20monkeypox%20virus%20was%20discovered,occasionally%20from%20animals%20to%20people [Accessed on 20th Feb 2024].

[3] Cherry J, Demmler-Harrison GJ, Kaplan SL, Steinbach W, Hotez PJ. Feigin and Cherry's textbook of pediatric infectious diseases. 8th edition. Elsevier; 2018.

[4] Smith SA, Kotwa GJ. Immune response to poxvirus infections in various animals. Crit Rev Microbiol 2022; 28: 149-185.

[5] Farasani A. Monkeypox virus: Future role in Human population. J Infect Public Health 2022; 15(11): 1270-1275.

[6] Gong Q, Wang C, Chuai X, Chiu S. Monkeypox virus: A re-emergent threat to humans. Virol Sin 2022; 37(4): 477-482.

[7] WHO director-general declares the ongoing monkeypox outbreak a public health emergency of international concern. [Online] Available from: https://www.who.int/europe/news/item/23-07-2022-who-director-general-declares-the-ongoing-monkeypox-outbreak-a-public-health-event-of-international-concern [Accessed on 20th Feb 2024].

[8] Mpox (Monkeypox) outbreak: Global trends. 2022-2023. [Online] Available from: https://worldhealthorg.shinyapps.io/mpx_global/ [Accessed on 21st Feb 2024].

[9] Ghazy RM, Elrewany E, Gebreal A, ElMakhzangy R, Fadl N, Elbanna EH, et al. Systematic review on the efficacy, effectiveness, safety, and immunogenicity of monkeypox vaccine. Vaccines (Basel) 2023; 11(11): 1708. doi: 10.3390/vaccines11111708.

[10] Saadh MJ, Ghadimkhani T, Soltani N, Abbassioun A, Daniel Cosme Pecho R, Taha A, et al. Progress and prospects on vaccine development against monkeypox infection. Microb Pathog 2023; 180. doi: 10.1016/j.micpath.2023.106156.

[11] Huang Y, Mu L, Wang W. Monkeypox: Epidemiology, pathogenesis, treatment and prevention. Signal Transduct Target Ther 2022; 7(1): 373. doi: 10.1038/s41392-022-01215-4.

[12] Ghazanfar A. Epidemiology, clinical features, diagnosis and management of monkeypox virus: A clinical review article. Cureus 2022; 14(8). doi: 10.7759/cureus.28598.

[13] Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, et al. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis 2022; 16(2). doi: 10.1371/journal.pntd.0010141.

[14] Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, et al. Infectious disease in an era of global change. Nat Rev Microbiol 2022; 20(4): 193-205.

[15] Moss B. Poxvirus DNA replication. Cold Spring Harb Perspect Biol 2013; 5(9). doi: 10.1101/cshperspect.a010199.

[16] Shchelkunova GA, Shchelkunov SN. Smallpox, monkeypox and other human orthopoxvirus infections. Viruses 2022; 15(1). doi: 10.3390/v15010103.

[17] Yu Z, Zhang W, Fu H, Zou X, Zhao M, Liang S, et al. Genomic analysis of Poxviridae and exploring qualified gene sequences for phylogenetics. Comput Struct Biotechnol J 2021; 19: 5479-5486.

[18] Coulson D, Upton C. Characterization of indels in poxvirus genomes. Virus Genes 2011; 42: 171-177.

[19] Wang L, Shang J, Weng S, Aliyari SR, Ji C, Cheng G, et al. Genomic annotation and molecular evolution of monkeypox virus outbreak in 2022. J Med Virol 2023; 95(1). doi: 10.1002/jmv.28036.

[20] Duggan AT, Perdomo MF, Piombino-Mascali D, Marciniak S, Poinar D, Emery MV, et al. 17th century variola virus reveals the recent history of smallpox. Curr Biol 2016; 26(24): 3407-3412.

[21] Saghazadeh A, Rezaei N. Poxviruses and the immune system: Implications for monkeypox virus. Int Immunopharmacol 2022; 113(Pt A). doi: 10.1016/j.intimp.2022.109364.

[22] Evangelista A, Bandeira M, Sena LM, Paula W, Cupertino M, Gomes A, et al. New variola (mpox) in Brazil: Epidemiological update and perspectives. Asian Pac J Trop Med 2022; 15(12): 525-528.

[23] Desingu PA, Rubeni TP, Sundaresan NR. Evolution of monkeypox virus from 2017 to 2022: In the light of point mutations. Front Microbiol 2022; 13: 1037598. doi: 10.3389/fmicb.2022.1037598.

[24] Parker S, Buller RM. A review of experimental and natural infections of animals with monkeypox virus between 1958 and 2012. Future Virol 2013; 8: 129-157.

[25] Krishna S, Kurrey C, Yadav M, Mahilkar S, Sonkar SC, Vishvakarma NK, et al. Insights into the emergence and evolution of monkeypox virus: Historical perspectives, epidemiology, genetic diversity, transmission, and preventative measures. Infect Med (Beijing) 2024; 3(2). doi: 10.1016/j.imj.2024.100105.

[26] Kumar P, Chaudhary B, Yadav N, Devi S, Pareek A, Alla S, et al. Recent advances in research and management of human monkeypox virus: An emerging global health threat. Viruses 2023; 15(4). doi: 10.3390/v15040937.

[27] Hudson PN, Self J, Weiss S, Braden Z, Xiao Y, Girgis NM, et al. Elucidating the role of the complement control protein in monkeypox pathogenicity. PLoS One 2012; 7(4). doi: 10.1371/journal.pone.0035086.

[28] Hutson CL, Gallardo-Romero N, Carroll DS, Clemmons C, Salzer JS, Nagy T, et al. Transmissibility of the monkeypox virus clades via respiratory transmission: Investigation using the prairie dog-monkeypox virus challenge system. PLoS One 2013; 8(2). doi: 10.1371/journal.pone.0055488.

[29] Brown K, Leggat PA. Human monkeypox: Current state of knowledge and implications for the future. Trop Med Infect Dis 2016; 1. doi: 10.3390/tropicalmed1010008.

[30] Reynolds MG, Damon IK. Outbreaks of human monkeypox after cessation of smallpox vaccination. Trends Microbiol 2012; 20: 80-87.

[31] Rezza G. Emergence of human monkeypox in West Africa. Lancet Infect Dis 2019; 19: 797-799.

[32] Alakunle E, Moens U, Nchinda G, Okeke MI. Monkeypox virus in Nigeria: Infection biology, epidemiology, and evolution. Viruses 2020; 12(11). doi: 10.3390/v12111257.

[33] Yinka-Ogunleye A, Aruna O, Dalhat M, Ogoina D, McCollum A, Disu Y, et al. Outbreak of human monkeypox in Nigeria in 2017-18: A clinical and epidemiological report. Lancet Infect Dis 2019; 19(8): 872-879.

[34] Isidro J, Borges V, Pinto M, Sobral D, Santos JD, Nunes A, et al. Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus. Nat Med 2022; 28(8): 1569-1572.

[35] Sereewit J, Lieberman NAP, Xie H, Bakhash SAKM, Nunley BE, Chung B, et al. ORF-interrupting mutations in monkeypox virus genomes from Washington and Ohio, 2022. Viruses 2022; 14(11). doi: 10.3390/v14112393.

[36] Happi C, Adetifa I, Mbala P, Njouom R, Nakoune E, Happi A, et al. Urgent need for a non-discriminatory and non-stigmatizing nomenclature for monkeypox virus. PLoS Biol 2022; 20(8). doi: 10.1371/journal.pbio.3001769.

[37] Hendrickson RC, Wang C, Hatcher EL, Lefkowitz EJ. Orthopoxvirus genome evolution: The role of gene loss. Viruses 2010; 2(9): 1933-1967.

[38] Glenn HL, de Matos AL, Villa N, McFadden G. Microscopic analysis of viral infection. Methods Mol Biol 2021; 2225: 163-177.

[39] Wolfe AM, Dunlap KM, Smith AC, Bartee MY, Bartee E. Myxoma virus M083 is a virulence factor which mediates systemic dissemination. J Virol 2018; 92(7). doi: 10.1128/JVI.02186-17.

[40] Smith GL. Vaccinia Virus Protein C6: A multifunctional interferon antagonist. Adv Exp Med Biol 2018; 1052: 1-7.

[41] Nucera F, Bonina L, Cipolla A, Pirina P, Hansbro PM, Adcock IM, et al. Poxviridae pneumonia. Adv Exp Med Biol 2024; 1451: 183-204.

[42] Lum FM, Torres-Ruesta A, Tay MZ, Lin RTP, Lye DC, Rénia L, et al. Monkeypox: Disease epidemiology, host immunity and clinical interventions. Nat Rev Immunol 2022; 22(10): 597-613.

[43] Moss B. Understanding the biology of monkeypox virus to prevent future outbreaks. Nat Microbiol 2024; 9(6): 1408-1416.

[44] Ndodo N, Ashcroft J, Lewandowski K, Yinka-Ogunleye A, Chukwu C, Ahmad A, et al. Distinct monkeypox virus lineages co-circulating in humans before 2022. Nat Med 2023; 29(9): 2317-2324.

[45] Liddament MT, Brown WL, Schumacher AJ, Harris RS. APOBEC3F properties and hypermutation preferences indicate activity against HIV-1 in vivo. Curr Biol 2004; 14: 1385-1391.

[46] Salter JD, Bennett RP, Smith HC. The APOBEC protein family: United by structure, divergent in function. Trends Biochem Sci 2016; 41: 578-594.

[47] Gigante CM, Korber B, Seabolt MH, Wilkins K, Davidson W, Rao AK, et al. Multiple lineages of monkeypox virus detected in the United States, 2021-2022. Science 2022; 378(6619): 560-565.

[48] Terajima M, Cruz J, Leporati AM, Demkowicz WE Jr, Kennedy JS, Ennis FA. Identification of vaccinia CD8+ T-cell epitopes conserved among vaccinia and variola viruses restricted by common MHC class I molecules, HLA-A2 or HLA-B7. Hum Immunol 2006; 67(7): 512-520.

[49] Lefkowitz E, Wang C, Upton C. Poxviruses: Past, present and future. Virus Res 2006; 117: 105-118.

[50] Ghabeshi S, Ghasemi S, Mousavizadeh L. The effective factors in human-specific tropism and viral pathogenicity in orthopoxviruses. Cell Biol Int 2023; 47: 341-351.

[51] Zhan XY, Zha GF, He Y. Evolutionary dissection of monkeypox virus: Positive Darwinian selection drives the adaptation of virus-host interaction proteins. Front Cell Infect Microbiol 2023; 12. doi: 10.3389/fcimb.2022.1083234.

[52] Yadav P, Devasurmutt Y, Tatu U. Phylogenomic and structural analysis of the monkeypox virus shows evolution towards increased stability. Viruses 2022; 15(1). doi: 10.3390/v15010127.

[53] Esposito JJ, Sammons SA, Frace AM, Osborne JD, Olsen-Rasmussen M, Zhang M, et al. Genome sequence diversity and clues to the evolution of variola (smallpox) virus. Science 2006; 313(5788): 807-812.

[54] Di Giulio DB, Eckburg PB. Human monkeypox: An emerging zoonosis. Lancet Infect Dis 2004; 4: 15-25.

[55] Parker S, Nuara A, Buller RML, Schultz DA. Human monkeypox: An emerging zoonotic disease. Future Microbiol 2007; 2: 17-34.

[56] Srivastava S, Kumar S, Jain S, Mohanty A, Thapa N, Poudel P, et al. The global monkeypox (Mpox) outbreak: A comprehensive review. Vaccines (Basel) 2023; 11(6). doi: 10.3390/vaccines11061093.

[57] Wang Y, Leng P, Zhou H. Global transmission of monkeypox virus-a potential threat under the COVID-19 pandemic. Front Immunol 2023; 14. doi: 10.3389/fimmu.2023.1174223.

[58] Cohen J. Monkeypox outbreak questions intensify as cases soar. Science 2022; 376(6596): 902-903.

[59] Seang S, Burrel S, Todesco E, Leducq V, Monsel G, Le Pluart D, et al. Evidence of human-to-dog transmission of monkeypox virus. Lancet 2022; 400(10353): 658-659.

[60] Shepherd W, Beard PM, Brookes SM, Frost A, Roberts H, Russell K, et al. The risk of reverse zoonotic transmission to pet animals during the current global monkeypox outbreak, United Kingdom, June to mid-September 2022. Euro Surveill 2022; 27(39). doi: 10.2807/1560-7917.ES.2022.27.39.2200758.

[61] Vaughan A, Aarons E, Astbury J, Brooks T, Chand M, Flegg P, et al. Human-to-human transmission of monkeypox virus, United Kingdom, October 2018. Emerg Infect Dis 2020; 26(4): 782-785.

[62] Huang Y, Mu L, Wang W. Monkeypox: Epidemiology, pathogenesis, treatment and prevention. Signal Transduct Target Ther 2022; 7(1): 373. doi: 10.1038/s41392-022-01215-4.

[63] Sah R, Abdelaal A, Reda A, Katamesh BE, Manirambona E, Abdelmonem H, et al. Monkeypox and its possible sexual transmission: Where are we now with its evidence? Pathogens 2022; 11(8). doi: 10.3390/pathogens11080924.

[64] McCollum AM, Damon IK. Human Monkeypox. Clin Infect Dis 2014; 58: 260-267.

[65] Ophinni Y, Frediansyah A, Sirinam S, Megawati D, Stoian AM, Enitan SS, et al. Monkeypox: Immune response, vaccination and preventive efforts. Narra J 2022; 2(3). doi: 10.52225/narra.v2i3.90.

[66] Iñigo Martínez J, Gil Montalbán E, Jiménez Bueno S, Martín Martínez F, Nieto Juliá A, Sánchez Díaz J, et al. Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022. Euro Surveill 2022; 27(27). doi: 10.2807/1560-7917.ES.2022.27.27.2200471.

[67] Karagoz A, Tombuloglu H, Alsaeed M, Tombuloglu G, AlRubaish AA, Mahmoud A, et al. Monkeypox (mpox) virus: Classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis. J Infect Public Health 2023; 16(4): 531-541.

[68] Johri N, Kumar D, Nagar P, Maurya A, Vengat M, Jain P. Clinical manifestations of human monkeypox infection and implications for outbreak strategy. Health Sci Rev 2022; 5. doi.org/ 10.1016/j.hsr.2022.100055.

[69] Diaz JH. The disease ecology, epidemiology, clinical manifestations, management, prevention, and control of increasing human infections with animal Orthopoxviruses. Wilderness Environ Med 2021; 32(4): 528-536.

[70] Chauhan RP, Fogel R, Limson J. Overview of diagnostic methods, disease prevalence and transmission of Mpox (Formerly monkeypox) in humans and animal reservoirs. Microorganisms 2023; 11(5). doi: 10.3390/microorganisms11051186.

[71] Bruneau RC, Tazi L, Rothenburg S. Cowpox viruses: A zoo full of viral diversity and lurking threats. Biomolecules 2023; 13(2). doi: 10.3390/biom13020325.

[72] Krankowska DC, Woźniak PA, Cybula A, Izdebska J, Suchacz M, Samelska K, et al. Cowpox: How dangerous could it be for humans? Case report. Int J Infect Dis 2021; 104: 239-241.

[73] Pauli G, Blümel J, Burger R, Drosten C, Gröner A, Gürtler L, et al. Orthopox viruses: Infections in humans. Transfus Med Hemother 2010; 37(6): 351-364.

[74] Waddell CJ, Filardo TD, Prasad N, Pellegrini GJ Jr, Persad N, Carson WC, et al. Possible undetected Mpox infection among persons accessing homeless services and staying in encampments - San Francisco, California, October-November 2022. Morb Mortal Wkly Rep 2023; 72(9): 227-231.

[75] Centers for Disease Control and Prevention. Vaccinia virus infection after sexual contact with a military smallpox vaccinee -Washington, 2010. Morb Mortal Wkly Rep 2010; 59(25): 773-775.

[76] Roper RL, Garzino-Demo A, Del Rio C, Bréchot C, Gallo R, Hall W, et al. Monkeypox (Mpox) requires continued surveillance, vaccines, therapeutics and mitigating strategies. Vaccine 2023; 41(20): 3171-3177.

[77] La Rosa G, Mancini P, Veneri C, Ferraro GB, Lucentini L, Iaconelli M, et al. Detection of monkeypox virus DNA in airport wastewater, Rome. Italy Emerg Infect Dis 2023; 29(1): 193-196.

[78] Wannigama DL, Amarasiri M, Hongsing P, Hurst C, Modchang C, Chadsuthi S, et al. Multiple traces of monkeypox detected in non-sewered wastewater with sparse sampling from a densely populated metropolitan area in Asia. Sci Total Environ 2023; 858(Pt 1). doi: 10.1016/j.scitotenv.2022.159816.

[79] Girón-Guzmán I, Díaz-Reolid A, Truchado P, Carcereny A, García-Pedemonte D, Hernáez B, et al. Spanish wastewater reveals the current spread of Monkeypox virus. Water Res 2023; 231. doi: 10.1016/j.watres.2023.119621.

[80] de Jonge EF, Peterse CM, Koelewijn JM, van der Drift AR, van der Beek RFHJ, Nagelkerke E, et al. The detection of monkeypox virus DNA in wastewater samples in the Netherlands. Sci Total Environ 2022; 852. doi: 10.1016/j.scitotenv.2022.158265.

[81] WastewaterSCAN Dashboard. [Online] Available from: data.wastewaterscan.org/ [Accessed on 21st Feb 2024].

[82] Roychoudhury P, Sereewit J, Xie H, Nunley E, Bakhash SM, Lieberman NAP, et al. Genomic analysis of early monkeypox virus outbreak strains, Washington, USA. Emerg Infect Dis 2023; 29: 644-646.

[83] Forni D, Molteni C, Cagliani R, Sironi M. Geographic structuring and divergence time frame of monkeypox virus in the endemic region. J Infect Dis 2022; 227: 742-751.

[84] Luna N, Ramírez AL, Muñoz M, Ballesteros N, Patiño LH, Castañeda SA, et al. Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: Emergence of a novel viral lineage? Travel Med Infect Dis 2022; 49. doi: 10.1016/j.tmaid.2022.102402.

[85] Nasri F, Kongkitimanon K, Wittig A, Cortés JS, Brinkmann A, Nitsche A, et al. MpoxRadar: A worldwide MPXV genomic surveillance dashboard. Nucleic Acids Res 2023; 51(W1): W331-W337.

[86] Reed KD, Melski JW, Graham MB, Regnery RL, Sotir MJ, Wegner MV, et al. The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med 2004; 350(4): 342-350.

[87] What clinicians need to know about monkeypox in the United States and other countries. [Online] Available from: https://stacks.cdc.gov/view/cdc/117869 [Accessed on 21st Feb 2024].

[88] Moore MJ, Rathish B, Zahra F. Mpox (Monkeypox) [Updated 2023 May 3]. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. [Online] Available from: https://www.ncbi.nlm.nih.gov/books/NBK574519/. [Accessed on 21st Feb 2024].

[89] Pérez-Martín ÓG, Hernández-Aceituno A, Dorta-Espiñeira MM, García-Hernández L, Larumbe-Zabala E. Atypical presentation of sexually-transmitted monkeypox lesions. Infect Dis (Lond) 2022; 54(12): 940-943.

[90] Luo Q, Han J. Preparedness for a monkeypox outbreak. Infect Med 2022; 1: 124-134.

[91] Reynolds MG, McCollum AM, Nguete B, Shongo Lushima R, Petersen BW. Improving the care and treatment of monkeypox patients in low-resource settings: Applying evidence from contemporary biomedical and smallpox biodefense research. Viruses 2017; 9(12): 380.

[92] Sánchez-Sampedro L, Perdiguero B, Mejías-Pérez E, García-Arriaza J, Di Pilato M, Esteban M. The evolution of poxvirus vaccines. Viruses 2015; 7(4): 1726-1803.

[93] Bonnekoh B, Falk K, Reckling KF, Kenklies S, Nitsche A, Ghebremedhin B, et al. Cowpox infection transmitted from a domestic cat. J Dtsch Dermatol Ges 2008; 6(3): 210-213.

[94] Nitsche A, Pauli G. Sporadic human cases of cowpox in Germany. Euro Surveill 2007; 12(4): E070419.3. doi: 10.2807/esw.12.16.03178-en.

[95] Ferrier A, Frenois-Veyrat G, Schvoerer E, Henard S, Jarjaval F, Drouet I, et al. Fatal cowpox virus infection in human fetus, France, 2017. Emerg Infect Dis 2021; 27(10): 2570-2577.

[96] Melekhin VV, Karem KL, Damon IK, Bloch KC. Encephalitis after secondary smallpox vaccination. Clin Infect Dis 2009; 48(1): e1-e2. doi: 10.1086/595555.

[97] Shanmugaraj B, Khorattanakulchai N, Phoolcharoen W. Emergence of monkeypox: Another concern amidst COVID-19 crisis. Asian Pac J Trop Med 2022; 15(5): 193-195.

[98] James J, Porkodi A, Sathyanarayanan V, Kala P, Rani J. An update on the pharmacological aspects of vaccines and antivirals for the management of monkeypox. J Pharmacol Pharmacother 2022; 13(4): 341-348.

[99] Vaccinia Immune Globulin Intravenous (Human). FDA. 2018. [Online] Available from: https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vaccinia-immune-globulin-intravenous-human. [Accessed on 10th May 2024].

[100] CDC. Mpox in the U.S. 2022. [Online] Available from: https://www.cdc.gov/poxvirus/monkeypox/clinicians/treatment.html [Accessed on 10th May 2024].

[101] Expanded Access IND Protocol: Use of vaccinia immune globulin intravenous (VIGIV, CNJ-016) for treatment of human orthopoxvirus infection in adults and children. [Online] Available from: https://www.cdc.gov/poxvirus/mpox/data/vigiv-protocol.pdf. [Accessed on 12th May 2024].

[102] CDC. Mpox in the U.S. 2022. [Online] Available from: https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/jynneos-vaccine.html. [Accessed on 12th May 2024].

[103] Monkeypox update: FDA authorizes emergency use of JYNNEOS vaccine to increase vaccine supply. FDA. 2022. [Online] Available from: https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply. [Accessed on 12th May 2024].

[104] Sharff KA, Tandy TK, Lewis PF, Johnson ES. Cardiac events following JYNNEOS vaccination for prevention of Mpox. Vaccine 2023; 41(22): 3410-3412.

[105] Rao AK, Petersen BW, Whitehill F, Razeq JH, Isaacs SN, Merchlinsky MJ, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for preexposure vaccination of persons at risk for occupational exposure to orthopoxviruses: Recommendations of the advisory committee on immunization practices - United States, 2022. MMWR Morb Mortal Wkly Rep 2022; 71(22): 734-742.

[106] Edghill-Smith Y, Bray M, Whitehouse CA, Miller D, Mucker E, Manischewitz J, et al. Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge. J Infect Dis 2005; 191(3): 372-381.

[107] Kenner J, Cameron F, Empig C, Jobes DV, Gurwith M. LC16m8: An attenuated smallpox vaccine. Vaccine 2006; 24(47-48): 7009-7022.

[108] Saijo M, Ami Y, Suzaki Y, Nagata N, Iwata N, Hasegawa H, et al. LC16m8, a highly attenuated vaccinia virus vaccine lacking expression of the membrane protein B5R, protects monkeys from monkeypox. J Virol 2006; 80(11): 5179-5188.

[109] Parker S, Handley L, Buller RM. Therapeutic and prophylactic drugs to treat orthopoxvirus infections. Future Virol 2008; 3: 595-612.

[110] Lederman ER, Davidson W, Groff HL, Smith SK, Warkentien T, Li Y, et al. Progressive vaccinia: Case description and laboratory-guided therapy with vaccinia immune globulin, ST-246, and CMX001. J Infect Dis 2012; 206(9): 1372-1385.

[111] Vora S, Damon I, Fulginiti V, Weber SG, Kahana M, Stein SL, et al. Severe eczema vaccinatum in a household contact of a smallpox vaccinee. Clin Infect Dis 2008; 46(10): 1555-1561.

[112] Petersen BW, Kabamba J, McCollum AM, Lushima RS, Wemakoy EO, Muyembe Tamfum JJ, et al. Vaccinating against monkeypox in the Democratic Republic of the Congo. Antiviral Res 2019; 162: 171-177.

[113] ClinicalTrials.gov. Follow-up of contact at risk of monkeypox infection: A prospective cohort study (MonkeyVax). Clinical trials. 2022. [Online] Available from: https://clinicaltrials.gov/study/NCT05438953 [Accessed on August 12 2023].

[114] Turner Overton E, Schmidt D, Vidojkovic S, Menius E, Nopora K, Maclennan J, et al. A randomized phase 3 trial to assess the immunogenicity and safety of 3 consecutively produced lots of freeze-dried MVA-BN ^® vaccine in healthy adults . Vaccine 2023; 41(2): 397-406.

[115] ClinicalTrials.gov. A study exploring the use of vaccine and antigen challenges for immune monitoring in healthy participants. [Online] Available from: https://clinicaltrials.gov/study/NCT03953196. [Accessed on 21st Feb 2024].

[116] ClinicalTrials.gov. Break-through infection following Mpox vaccination (REMAIN). [Online] Available from https://clinicaltrials.gov/study/NCT05522296 [Accessed on 21st Feb 2024].