Monkeypox, a zoonotic disease, was first discovered in monkeys used for research in 1958 and is spread primarily among animals. The first human case of monkeypox was found in the Democratic Republic of Congo (DRC) in 1970, and since then, monkeypox has been endemic to a number of African countries, including Nigeria, the DRC, and the Central African Republic. Monkeypox cases outside of Africa are usually contracted as a result of traveling to Africa.
In the first half of 2022, monkeypox began to spread in Europe and North America, and on July 23, 2022, WHO Director General Tandace declared the monkeypox outbreak to be a "Public Health Emergency of International Concern" (PHEIC). The 2022 outbreak has caused 8,000 cases in more than 110 countries and territories around the world. The 2022 outbreak has caused more than 80,000 infections in more than 110 countries and territories worldwide, including approximately 30,000 cases in the United States.
Unlike previous monkeypox outbreaks, this one has spread rapidly around the world and is predominantly prevalent among men who have sex with men. The strain responsible for this monkeypox outbreak has been identified as the West African B.1 spectrum branch IIb monkeypox virus.
On September 20, 2023, researchers at Harvard Medical School published a research paper in the journal Cell entitled "Mpox infection protects against re-challenge in rhesus macaques".
The study demonstrated that natural immunity induced by all three routes of infection with the monkeypox virus—intravenous, intradermal, and rectal injections—induced protective efficacy against re-challenge of the monkeypox virus. These observations provide mechanistic insights into the pathogenesis and immunity of monkeypox. In addition, this study demonstrates the usefulness of this non-human primate model for testing monkeypox vaccines and treatments.
In the context of the current monkeypox epidemic, our understanding of monkeypox virus pathogenesis and immunity remains limited. In particular, the current monkeypox outbreak is spreading primarily among men who have sex with men (MSM) populations, and it is not clear whether this nontraditional route of infection leads to natural immunity to prevent reinfection after infection and then tract. And this information is critical to the development of vaccine strategies, epidemiological modeling, and public health approaches related to the vaccine.
To explore this question, the research team constructed a model of monkeypox virus-infected rhesus monkeys using the current outbreak strain of monkeypox and evaluated the virologic, immunologic, histopathologic, transcriptomic, and proteomic features of acute infection and protective immunity to reinfection.
The team infected 18 rhesus monkeys by intravenous, intradermal, and rectal routes of injection and observed robust antibody responses and T-cell responses in rhesus monkeys following all three routes of infection. Substantial skin lesions and high plasma monkeypox virus loads were observed after infection by the intravenous and intradermal routes. Skin lesions peaked on day 10 post-infection and subsided on day 28 post-infection.
On day 28, the team infected all recovering rhesus monkeys and three previously uninfected rhesus monkeys with the monkeypox virus. The results showed that all recovering rhesus monkeys were protected from re-infection with monkeypox. Transcriptomics studies showed that upon initial infection with monkeypox virus, the activation of innate immune responses and inflammatory responses as well as T- and B-cell signaling were markedly upregulated, collagen formation and extracellular matrix organization were downregulated, and T-cell and plasma cell responses were rapidly activated, which provided new insights into the pathogenesis of acute monkeypox.
In response to monkeypox virus reattack, innate and inflammatory signals were markedly reduced, whereas T-cell and plasma cell signals were activated very rapidly, suggesting that immune memory cells and humoral immune responses may be critical to the protective effect against reattack.
Overall, these observations provide mechanistic insights into the pathogenesis and immunity of monkeypox. In addition, the study demonstrates that this non-human primate model is useful for testing monkeypox vaccines and treatments.
These data provide key mechanistic insights into monkeypox pathogenesis and immunity and also demonstrate that this non-human primate model is useful for evaluating monkeypox vaccines and therapeutics.