Fighting the monkeypox virus: Genetics as a predictor of vaccinia vaccine effectiveness

Vaccination Variants
Fighting monkeypox with vaccinia vaccines

Monkeypox is a painful and debilitating viral infection. Cases have been rising rapidly since April, causing the World Health Organization to declare the monkeypox outbreak a global health emergency as of July 20221. Thankfully, science is on our side and vaccinia-based vaccines may be the key to stopping another pandemic.

Understanding the vaccinia-based vaccine

Vaccinia-based vaccines contain inactivated or non-pathological viruses. These types of vaccines are being explored for use against monkeypox as this type of vaccine is behind the eradication of the smallpox outbreak that wiped out millions worldwide2. Recent evidence demonstrates that these vaccines have been effective against the monkeypox virus due to a concept known as cross-reactivity.

Cross-reactivity simply means that there are similarities within each virus which may mean similar targets to develop immunity2. However, the virus responsible for smallpox is genetically different from the virus responsible for monkeypox. Due to this genetic variation, it is unknown whether the vaccinia-based vaccines would be effective2

To gain further understanding, a group of researchers accessed public databases to compare the genetic code of the vaccinia virus pre-1980s (smallpox) and compared these to the 2022 monkeypox viruses2. The exploration focused on the segments of the viruses that are targeted by the immune system, known as epitopes. Comparing epitopes between the viruses could show how effective the vaccinia-based vaccine may be against the 2022 monkeypox virus2.

The researchers then sought to determine the degree of genetic similarity among the epitopes that are recognized by our T cells. T cells are paramount in fighting pathogens and are responsible for inducing a range of immune responses against different infectious agents1,3.  These researchers found similarities among the epitopes recognized by our T cells which means there is a positive association between the vaccinia-based vaccine and the activation and function of our T cells2.

The take-home message

The 2022 monkeypox virus contains mostly similar epitopes to that of the vaccinia virus. This implies that the vaccinia-based vaccine may be the defense needed against this monkeypox virus and its strains2,3.

Despite these encouraging results, additional studies are warranted to discover the specificity of immune responses based on genetic differences, but similarities of epitopes observed between the 2022 monkeypox virus and the vaccinia virus3.


  1. Nuzzo JB, Borio LL, Gostin LO. The WHO Declaration of Monkeypox as a Global Public Health Emergency. JAMA. 2022;328(7):615–617. doi:10.1001/jama.2022.12513
  2. Ahmed SF, Sohail MS, Quadeer AA, Mckay MR. Vaccinia-Virus-Based Vaccines are Expected to Elicit Highly Cross-Reactive Immunity to the 2022 Monkeypox Virus. Viruses. 2022;14(9):1960. doi:10.3390/v14091960.
  3. Navollotskaya EV. The Second Life of Antibodies. Biochemistry (Moscow). 2014; 79: 1-7.
  1. Laidlaw BJ, Craft JE, Kaech SM. The Multifaceted Role of CD4(+) T Cells in CD8(+) T Cell Memory. Nat Rev Immunol. 2016;16(2):102-111. doi:10.1038/nri.2015.10

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