Comparative Study of World Health Organization Recommended Smallpox Vaccine to Prevent Monkeypox
DOI:
https://doi.org/10.35451/0ejez036Keywords:
ACAM2000, LC16, MVA-BN, Monkeypox, VaccineAbstract
Background: Monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV) from the Orthopoxvirus genus and has shown a global increase in cases since 2022. Currently, no specific vaccine is available; however, smallpox vaccines provide cross-protection and are recommended by the World Health Organization (WHO) for prevention. Objective: This review aims to compare the efficacy and safety of WHO-recommended smallpox vaccines (MVA-BN, LC16m8, and ACAM2000) in preventing monkeypox. Methods: This literature review searched Google Scholar and Publish or Perish with the keywords “monkeypox vaccine”, “MVA-BN,” “LC16,” “ACAM2000,” “efficacy,” and “safety.” Articles published between 2015 and 2025 were included. Of 155 identified records, 9 met the inclusion criteria and were analyzed. Results: All vaccines were effective in preventing monkeypox through humoral and cellular immune responses. MVA-BN showed the highest efficacy and best safety profile, while LC16m8 provided long-term protection with mild adverse effects. ACAM2000 was effective but associated with mild cardiovascular adverse events, limiting its use in certain populations. Conclusion: WHO-recommended smallpox vaccines are effective and relatively safe, with MVA-BN considered the most optimal option. Further development of monkeypox-specific vaccines using mRNA and DNA technologies is needed, as these platforms allow more specific antigen targeting and may enhance immune response and safety.
Downloads
References
[1] E. Petersen et al., “Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention,” Infect. Dis. Clin. North Am., vol. 33, no. 4, pp. 1027–1043, 2019, doi: 10.1016/j.idc.2019.03.001.
[2] J. G. Rizk, G. Lippi, B. M. Henry, D. N. Forthal, and Y. Rizk, “Prevention and Treatment of Monkeypox,” Drugs, vol. 82, no. 9, pp. 957–963, 2022, doi: 10.1007/s40265-022-01742-y.
[3] J. P. Thornhill et al., “Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022,” N. Engl. J. Med., vol. 387, no. 8, pp. 679–691, 2022, doi: 10.1056/nejmoa2207323.
[4] L. Budiyarto, A. A. Sabila, and H. C. Putri, “Infeksi Cacar Monyet (Monkeypox),” J. Med. Hutama, vol. 4, no. 02 Januari, pp. 3224–3236, 2023.
[5] WHO, “Vaccines and Immunization for Monkeypox: Interim Guidance,” 2022. [Online]. Available: https://iris.who.int/bitstream/handle/10665/364527/WHO-MPX-Immunization-2022.3-eng.pdf
[6] H. Laurenson-Schafer et al., “Description of the first global outbreak of mpox: an analysis of global surveillance data,” Lancet Glob. Heal., vol. 11, no. 7, pp. e1012–e1023, 2023, doi: 10.1016/S2214-109X(23)00198-5.
[7] H. Kadriyan, “Kedaruratan Kesehatan Masyarakat akibat Cacar Monyet ( Monkeypox / Mpox ),” Lomb. Med. J., vol. 3, no. 3, pp. 110–111, 2024.
[8] KEMENKES RI, “88 Kasus Konfirmasi Mpox di Indonesia, Seksual Sesama Jenis Jadi Salah Satu Penyebab – Sehat Negeriku,” 2024. [Online]. Available: https://sehatnegeriku.kemkes.go.id/baca/rilis-media/20240818/1546252/88-kasus-konfirmasi-mpox-di-indonesia-seksual-sesama-jenis-jadi-salah-satu-penyebab/
[9] WHO, “Monkeypox,” 2024. [Online]. Available: https://www.who.int/news-room/fact-sheets/detail/mpox
[10] L. Goyal, K. Ajmera, R. Pandit, and T. Pandit, “Prevention and Treatment of Monkeypox: A Step-by-Step Guide for Healthcare Professionals and General Population,” Cureus, vol. 14, no. Cdc, pp. 1–13, 2022, doi: 10.7759/cureus.28230.
[11] CDC, “Clinical Treatment of Mpox,” 2024. [Online]. Available: https://www.cdc.gov/mpox/hcp/clinical-care/index.html#:~:text=Currently there is no treatment,them recover without medical treatment.
[12] M. J. Saadh et al., “Progress and prospects on vaccine development against monkeypox infection,” Microb. Pathog., vol. 180, no. February, p. 106156, 2023, doi: 10.1016/j.micpath.2023.106156.
[13] H. Liu et al., “Global perspectives on smallpox vaccine against monkeypox: a comprehensive meta-analysis and systematic review of effectiveness, protection, safety and cross-immunogenicity,” Emerg. Microbes Infect., vol. 13, no. 1, pp. 1–15, 2024, doi: 10.1080/22221751.2024.2387442.
[14] A. Xia et al., “Cross-reactive antibody response to Monkeypox virus surface proteins in a small proportion of individuals with and without Chinese smallpox vaccination history,” BMC Biol., vol. 21, no. 1, pp. 1–15, 2023, doi: 10.1186/s12915-023-01699-8.
[15] C. Chakraborty, M. Bhattacharya, A. Ranjan Sharma, and K. Dhama, “Monkeypox virus vaccine evolution and global preparedness for vaccination,” Int. Immunopharmacol., vol. 113, no. PA, p. 109346, 2022, doi: 10.1016/j.intimp.2022.109346.
[16] B. Perdiguero et al., “Highly Attenuated Poxvirus-Based Vaccines Against Emerging Viral Diseases,” J. Mol. Biol., vol. 435, no. 15, 2023, doi: 10.1016/j.jmb.2023.168173.
[17] A. A. Apriliyanti, I. Setiawan, and A. Ferdiyansyah, “Sosialisasi Tentang Vaksinasi Covid-19 Di Kelurahan Biru Kecamatan Tanete Riattang Kabupaten Bone,” GEMAKES J. Pengabdi. Kpd. Masy., vol. 1, no. 2, pp. 60–64, 2021, doi: 10.36082/gemakes.v1i2.405.
[18] F. Gao et al., “Cross-reactive immune responses to monkeypox virus induced by MVA vaccination in mice,” Virol. J., vol. 20, no. 1, pp. 1–10, 2023, doi: 10.1186/s12985-023-02085-0.
[19] R. B. Kennedy, I. G. Ovsyannikova, R. M. Jacobson, and G. A. Poland, “The immunology of smallpox vaccines,” Curr. Opin. Immunol., vol. 21, no. 3, pp. 314–320, 2009, doi: 10.1016/j.coi.2009.04.004.
[20] E. Li et al., “Duration of humoral immunity from smallpox vaccination and its cross-reaction with Mpox virus,” Signal Transduct. Target. Ther., vol. 8, no. 1, pp. 1–7, 2023, doi: 10.1038/s41392-023-01574-6.
[21] Y. Sang et al., “Monkeypox virus quadrivalent mRNA vaccine induces immune response and protects against vaccinia virus,” Signal Transduct. Target. Ther., vol. 8, no. 1, 2023, doi: 10.1038/s41392-023-01432-5.
[22] E. R. Whitehouse et al., “Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo during 2011-2015,” J. Infect. Dis., vol. 223, no. 11, pp. 1870–1878, 2021, doi: 10.1093/infdis/jiab133.
[23] A. Volz and G. Sutter, Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development, 1st ed., vol. 97. Elsevier Inc., 2017. doi: 10.1016/bs.aivir.2016.07.001.
[24] R. N. Greenberg et al., “Equivalence of freeze-dried and liquid-frozen formulations of MVA-BN as smallpox and mpox vaccine,” Hum. Vaccines Immunother., vol. 20, no. 1, 2024, doi: 10.1080/21645515.2024.2384189.
[25] N. Ghosh et al., “Clinical Strategies and Therapeutics for Human Monkeypox Virus: A Revised Perspective on Recent Outbreaks,” Viruses, vol. 15, no. 7, pp. 1–15, 2023, doi: 10.3390/v15071533.
[26] Y. Nishiyama, T. Fujii, Y. Kanatani, Y. Shinmura, H. Yokote, and S. Hashizume, “Freeze-dried live attenuated smallpox vaccine prepared in cell culture ‘LC16-KAKETSUKEN’: Post-marketing surveillance study on safety and efficacy compliant with Good Clinical Practice,” Vaccine, vol. 33, no. 45, pp. 6120–6127, 2015, doi: 10.1016/j.vaccine.2015.09.067.
[27] A. K. Gupta, M. Talukder, T. Rosen, and V. Piguet, “Differential Diagnosis, Prevention, and Treatment of mpox (Monkeypox): A Review for Dermatologists,” Am. J. Clin. Dermatol., vol. 24, no. 4, pp. 541–556, 2023, doi: 10.1007/s40257-023-00778-4.
[28] D. Makkar, “The latest news for May 2022 all you need to know on monkeypox,” IP Int. J. Med. Microbiol. Trop. Dis., vol. 8, no. 3, pp. 183–195, 2022, doi: 10.18231/j.ijmmtd.2022.039.
[29] M. M. Christodoulidou and N. A. Mabbott, “Efficacy of smallpox vaccines against Mpox infections in humans,” Immunother. Adv., vol. 3, no. 1, pp. 1–9, 2023, doi: 10.1093/immadv/ltad020.
[30] et al. Asquith, W., “Characterizing the acute antibody response of monkeypox and MVA‐BN vaccine.pdf,” J. Med. Virol., vol. 96, no. e29407, pp. 1–9, 2023, [Online]. Available: https://doi.org/10.1002/jmv.29407
[31] V. Larasati, R. Sabloak, R. S. P. Rasyid, E. F. Zulissetiana, S. Susilawati, and S. Fertilita, “Hubungan Kebiasaan Olahraga Dengan Kadar Antibodi Immunoglobulin G Setelah Vaksinasi Covid 19,” J. Kedokt. dan Kesehat. Publ. Ilm. Fak. Kedokt. Univ. Sriwij., vol. 10, no. 1, pp. 39–52, 2023, doi: 10.32539/jkk.v10i1.19620.
[32] I. Sebina and M. Pepper, “Humoral immune responses to infection: common mechanisms and unique strategies to combat pathogen immune evasion tactics,” Curr. Opin. Immunol., vol. 51, pp. 46–54, 2018, doi: 10.1016/j.coi.2018.02.001.
[33] I. Iizuka et al., “A single vaccination of nonhuman primates with highly attenuated smallpox vaccine, LC16m8, provides long-term protection against monkeypox,” Jpn. J. Infect. Dis., vol. 70, no. 4, pp. 408–415, 2017, doi: 10.7883/yoken.JJID.2016.417.
[34] M. Shannon Keckler et al., “Imvamune® and acam2000® provide different protection against disease when administered postexposure in an intranasal monkeypox challenge prairie dog model,” Vaccines, vol. 8, no. 3, pp. 1–23, 2020, doi: 10.3390/vaccines8030396.
[35] N. Tomita et al., “Evaluating the Immunogenicity and Safety of a Smallpox Vaccine to Monkeypox in Healthy Japanese Adults: A Single-Arm Study,” Life, vol. 13, no. 3, 2023, doi: 10.3390/life13030787.
[36] E. Turner Overton 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, vol. 41, no. 2, pp. 397–406, 2023, doi: 10.1016/j.vaccine.2022.10.056.
[37] D. J. Faix et al., “Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel,” Vaccine, vol. 38, no. 46, pp. 7323–7330, 2020, doi: 10.1016/j.vaccine.2020.09.037.
[38] E. M. Mucker et al., “A Nucleic Acid-Based Orthopoxvirus Vaccine Targeting the Vaccinia Virus L1, A27, B5, and A33 Proteins Protects Rabbits against Lethal Rabbitpox Virus Aerosol Challenge,” J. Virol., vol. 96, no. 3, 2022, doi: 10.1128/jvi.01504-21.
[39] I. Garcia-Atutxa, P. Mondragon-Teran, A. Huerta-Saquero, and F. Villanueva-Flores, “Advancements in monkeypox vaccines development: a critical review of emerging technologies,” Front. Immunol., vol. 15, no. October, pp. 1–23, 2024, doi: 10.3389/fimmu.2024.1456060.
[40] Y. Wang, Z. Zhang, J. Luo, X. Han, Y. Wei, and X. Wei, “mRNA vaccine: a potential therapeutic strategy,” Mol. Cancer, vol. 20, no. 1, pp. 1–23, 2021, doi: 10.1186/s12943-021-01311-z.
[41] W. Ho, M. Gao, F. Li, Z. Li, X. Q. Zhang, and X. Xu, “Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery,” Adv. Healthc. Mater., vol. 10, no. 8, pp. 1–17, 2021, doi: 10.1002/adhm.202001812.
[42] Z. Fang et al., “Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens,” Cell Res., vol. 33, no. 5, pp. 407–410, 2023, doi: 10.1038/s41422-023-00792-5.
[43] E. Li et al., “An mpox quadrivalent mRNA vaccine protects mice from lethal vaccinia virus challenge,” Antiviral Res., vol. 230, no. June, p. 105974, 2024, doi: 10.1016/j.antiviral.2024.105974.
[44] X. Wang, Z. Gu, S. Sheng, R. Song, and R. Jin, “The Current State and Progress of Mpox Vaccine Research,” China CDC Wkly., vol. 6, no. 7, pp. 118–125, 2024, doi: 10.46234/ccdcw2024.025.
[45] N. Zhang et al., “Multi-valent mRNA vaccines against monkeypox enveloped or mature viron surface antigens demonstrate robust immune response and neutralizing activity,” Sci. China Life Sci., vol. 66, no. 10, pp. 2329–2341, 2023, doi: 10.1007/s11427-023-2378-x.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Reas Najla Anugrah, Ahsanal Kasasiah

This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright in each article is the property of the Author.





















