Previous Vaccines Based on Vaccinia Virus (VACV) Are Effective Against Novel Monkeypox Virus MPXV-2022

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More than 52,000 cases have been confirmed in more than 90 countries and territories since a novel monkeypox virus infection was detected in humans in May 2022. The rapid spread of the virus has sparked global concern, and on July 23 the World Health Organization (WHO) declared the 2022 monkeypox outbreak a global health emergency of international concern. The underlying determinants of the MPXV-2022 outbreak remain unclear, but the new monkeypox virus belongs to the West African MPXV clade (MPXV-WA) based on phylogenetic analysis of genome sequences reported on GISAID in at least 15 countries.

 

There are three main types of VACV-based vaccines in the past. First-generation vaccines included live vaccinia viruses, such as Dryvax, which were used to eradicate smallpox in the last century. During the African monkeypox outbreak in the 1980s, first-generation VACV-based vaccines were reported to provide 85% protection against MPXV in humans. While the WHO and some countries maintain stocks of these vaccines, their use against MPXV is not recommended for safety reasons. ACAM2000 is a second-generation vaccine, also based on live VACV, but with a better safety profile than the first-generation vaccine. The vaccine is currently available in the United States for use against monkeypox under expanded access investigational new drug applications. The third-generation vaccine, Bavarian Nordic Modified Vaccinia Virus Ankara (MVA-BN), is currently recommended by the World Health Organization and the U.S. Centers for Disease Control and Prevention (CDC) for the control of high-risk groups of the current monkeypox outbreak. MVA-BN is a highly attenuated VACV-based vaccine that cannot replicate in humans and is safer and easier to manage than the previous generation of vaccines, but MVA-BN is currently available in limited numbers. Both ACAM2000 and MVA-BN vaccines are known to show protection against MPXV in animal models, but these results are reported for the Congo Basin MPXV clade (MPXV-CB). There is still a lack of scientific data on the immune efficacy of the three vaccines against viruses belonging to the MPXV-WA clade.

 

This year’s outbreak of the MPXV-2022 virus carries different genetic variants that have the potential to influence vaccine-induced immune recognition. A few weeks after the emergence of the new strain, a genomic study of MPXV-2022 was led by Professor Matthew MCKAY, a researcher at the Center for Future Research at the University of Melbourne, and Professor Ahmed Abdul QUADEER, an assistant researcher at the Hong Kong University of Science and Technology, to determine whether the genetic mutations observed in MPXV-2022 may affect the VACV-vaccine-induced immune response to monkeypox. The results were published in Virus.

 

Professor MCKAY is also an adjunct professor at Hong Kong University of Science and Technology. “Vaccines based on VACV have previously shown high efficacy against monkeypox virus and are an important epidemic prevention and control measure,” he said. “However, given that MPXV-2022 is a new monkeypox virus, we still lack scientific data to determine how the human immune response elicited by VACV-based vaccines recognizes MPXV-2022 and provides protection against disease.”

 

Using genomic and immunological data, the team assessed genetic similarity and differences between VACV and MPXV-2022, particularly within protein regions targeted by vaccine-induced neutralizing antibodies or T cells.

 

Professor McKay said: “Although we found a small number of different mutations with potential immunological effects in MPXV-2022, our study more broadly showed that VACV and MPXV-2022 are highly similar in genes in immune system recognition regions targeted by vaccination.” “While sequencing and immunological data provide evidence to predict robust immune responses, clinical studies are needed to determine the exact efficacy of these vaccines against MPXV-2022.”

 

Professor Quadeer said the findings were reassuring. “According to our analysis, we expect that VACV-based vaccines generate immune responses that recognize MPXV-2022 well, as in the past for monkeypox viruses.” “Our data further support the use of the globally recommended VACV vaccine against MPXV-2022.”

 

The World Health Organization recommends primary prevention vaccines against the new monkeypox virus for individuals at high risk of contact, also known as pre-contact prophylaxis.

 

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