Monkeypox Vaccination

September 26, 2022

Monkeypox virus (MPV) is a double-stranded DNA zoonotic orthopoxvirus with symptoms similar to smallpox, albeit less severe and with notably lower mortality5,10. Monkeypox was isolated and identified in 1958 when a cargo of Macaca cynomolgus developed nonfatal pox-like lesions symptoms at a Copenhagen, Denmark, research facility1,5. However, MPV was isolated from a 9-year-old child in a rural Democratic Republic of Congo (DRC) suspected of having smallpox in August 19705. Human cases of MPV have been recorded in 11 African nations since 1970, with a median age of thirty-one years.6 Though previous outbreaks were small in scale, maintaining preparedness is important for public health, especially in terms of rolling out monkeypox vaccination programs as needed. 

Scientists have long postulated that monkeypox’s increased incidence may be attributed to diminishing orthopoxvirus immunity once the smallpox was eradicated in the 1980s and vaccination efforts ceased.9 Because of this diminishing immunity in the last decade, monkeypox has again become clinically relevant.6 MPV is transmitted by close personal contact; many cases outside of endemic areas in Africa have been transmitted through sexual contact, particularly in the ongoing outbreak.4 Currently, there is no specific clinical therapeutic for monkeypox virus infections.3 The Centers for Illness Control and Prevention advises administering the smallpox vaccine four days post-exposure to prevent the disease and lessen the severity of symptoms within two weeks.5,6 

Since the eradication of smallpox, vaccine technology has made significant strides.7 All first-generation vaccines used live, replication-capable viruses, with the majority derived from calf lymph.7 A successful monkeypox vaccination resulted in the formation of a lesion at the site of injection, which generated an infectious virus.7 However, potential adverse events include the risk of autoinoculation to other body regions and unintended transfer to other persons.7 In contrast, second-generation vaccines utilize modern manufacturing techniques and tissue cell culture.7 As a result, they are less likely to be contaminated by accidental substances. 7 Nevertheless, both first- and second-generation vaccines include replication-competent vaccinia virus, increasing potential side effects.7 Modified Vaccinia Ankara (MVA), third-generation vaccines, are likewise cultivated in tissue culture, prepared using modern manufacturing techniques and utilizes attenuatedviruses with favorable safety profiles.7

Poxviruses modified to express foreign gene products are well-established techniques in biomedical research for developing novel vaccines and therapeutics.11 IMVAMUNE, a third-generation smallpox vaccine evaluated in HIV-positive and atopic dermatitis-afflicted individuals, was created for those with a higher risk of adverse effects.11 The third-generation vaccine is generated from MVA and has lost its capacity to reproduce in mammalian cells.11 As a result, it no longer causes lesions at the injection site and poses no danger of autoinoculation, unintentional transfer, or systemic dissemination.11 

Discontinuing smallpox vaccination has created an ecological gap in which an increasing proportion of the population has diminishing or nonexistent protection against monkeypox.8 With monkeypox now a disease of global significance and concern, there are limited medical resources to stop its spread.2 The significant shortage of monkeypox vaccines, compared to current demands and delays in vaccine manufacturing ramp-up, even in high-income countries, pose issues for countries combating the rapid spread of MPV.2  Public health officials are now considering shifting focus to the cost/benefit of population-level vaccination and alternate vaccination approaches, such as targeting impacted regions, contacts, and health care providers affected by monkeypox to prevent a pandemic.8 


  1. Cho, C. T., & Wenner, H. A. (1973). Monkeypox virus. Bacteriological reviews, 37(1), 1–18.   
  1. Gruber M. F. (2022). Current status of monkeypox vaccines. NPJ vaccines, 7(1), 94.  
  1. Hraib, M., Jouni, S., Albitar, M. M., Alaidi, S., & Alshehabi, Z. (2022). The outbreak of monkeypox 2022: An overview. Annals of medicine and surgery (2012), 79, 104069. 
  1. Iñigo Martínez, J., Gil Montalbán, E., Jiménez Bueno, S., Martín Martínez, F., Nieto Juliá, A., Sánchez Díaz, J., García Marín, N., Córdoba Deorador, E., Nunziata Forte, A., Alonso García, M., Humanes Navarro, A. M., Montero Morales, L., Domínguez Rodríguez, M. J., Carbajo Ariza, M., Díaz García, L. M., Mata Pariente, N., Rumayor Zarzuelo, M., Velasco Rodríguez, M. J., Aragón Peña, A., Rodríguez Baena, E., … Arce Arnáez, A. (2022). Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, 27(27), 2200471. 
  1. Moore MJ, Rathish B, Zahra F. Monkeypox. [Updated 2022 Jul 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: 
  1. Nguyen, P. Y., Ajisegiri, W. S., Costantino, V., Chughtai, A. A., & MacIntyre, C. R. (2021). Reemergence of Human Monkeypox and Declining Population Immunity in the Context of Urbanization, Nigeria, 2017-2020. Emerging infectious diseases, 27(4), 1007–1014. 
  1. Petersen, B. W., Kabamba, J., McCollum, A. M., Lushima, R. S., Wemakoy, E. O., Muyembe Tamfum, J. J., Nguete, B., Hughes, C. M., Monroe, B. P., & Reynolds, M. G. (2019). Vaccinating against monkeypox in the Democratic Republic of the Congo. Antiviral research, 162, 171–177. 
  1. Petersen, E., Kantele, A., Koopmans, M., Asogun, D., Yinka-Ogunleye, A., Ihekweazu, C., & Zumla, A. (2019). Human Monkeypox: Epidemiologic and Clinical Characteristics, Diagnosis, and Prevention. Infectious disease clinics of North America, 33(4), 1027–1043.  
  1. Rimoin, A. W., Mulembakani, P. M., Johnston, S. C., Lloyd Smith, J. O., Kisalu, N. K., Kinkela, T. L., Blumberg, S., Thomassen, H. A., Pike, B. L., Fair, J. N., Wolfe, N. D., Shongo, R. L., Graham, B. S., Formenty, P., Okitolonda, E., Hensley, L. E., Meyer, H., Wright, L. L., & Muyembe, J. J. (2010). Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo. Proceedings of the National Academy of Sciences of the United States of America, 107(37), 16262–16267. 
  1. Rizk, J. G., Lippi, G., Henry, B. M., Forthal, D. N., & Rizk, Y. (2022). Prevention and Treatment of Monkeypox. Drugs, 82(9), 957–963. 
  1. Volz, A., & Sutter, G. (2017). Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development. Advances in virus research, 97, 187–243.