April 28, 2024

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Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection

Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection



Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection.

Monkeypox is a zoonotic disease first discovered in 1958 among research monkeys and primarily transmitted among animals.

In 1970, the first human case of monkeypox was reported in the Democratic Republic of the Congo (DRC), and since then, monkeypox has been endemic in several African countries, including Nigeria, DRC, and the Central African Republic.

Cases of monkeypox outside Africa typically result from travel to the continent.

 

However, in the first half of 2022, monkeypox began spreading in Europe and North America. On July 23, 2022, the Director-General of the World Health Organization (WHO), Dr. Tedros Adhanom Ghebreyesus, declared the monkeypox outbreak a “Public Health Emergency of International Concern” (PHEIC). As of 2023, the monkeypox outbreak, which started in 2022, has caused over 80,000 infections in more than 110 countries and regions worldwide, with approximately 30,000 cases reported in the United States.

Unlike previous monkeypox outbreaks, this one has spread rapidly on a global scale and is predominantly affecting men who have sex with men (MSM). The strain responsible for this outbreak has been identified as the West African B.1 lineage IIb branch of monkeypox virus.

On September 20, 2023, researchers from Harvard Medical School published a study in the journal Cell titled “Mpox Infection Protects Against Re-challenge in Rhesus Macaques.”

The study demonstrates that natural immunity induced by infection with monkeypox virus through intravenous, intradermal, and rectal routes provides protection against re-infection with the virus. These findings offer insights into the pathogenesis and immunity of monkeypox. Additionally, the study highlights the utility of non-human primate models for testing monkeypox vaccines and treatments.

 

Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection

 

 

Given the current monkeypox outbreak, our understanding of the pathogenesis and immunity of monkeypox remains limited. In particular, it is unclear whether non-traditional routes of infection, such as those seen in this outbreak among MSM, lead to natural immunity that prevents re-infection. This information is crucial for informing vaccine strategies, epidemiological modeling, and public health interventions.

To address this question, the research team constructed a rhesus macaque model of monkeypox infection using the current outbreak strain and assessed virological, immunological, histopathological, transcriptomic, and proteomic characteristics of acute infection and protective immunity against re-infection.

They infected 18 rhesus macaques through intravenous, intradermal, and rectal routes and observed robust antibody and T-cell responses following all three infection routes. Intravenous and intradermal infections resulted in extensive skin lesions and high plasma monkeypox virus loads. Skin lesions peaked on day 10 post-infection and regressed by day 28 post-infection.

On day 28, the research team challenged all convalescent macaques and three previously uninfected macaques with monkeypox virus. The results showed that all convalescent macaques were protected and did not re-develop monkeypox.

Transcriptomic analysis revealed significant upregulation of innate immune responses, inflammation, and activation of T-cell and B-cell signaling pathways during primary monkeypox infection, providing new insights into the pathogenesis of acute monkeypox.

Upon re-challenge with monkeypox virus, there was a noticeable decrease in innate and inflammatory signaling, while T-cell and plasma cell signaling were rapidly activated. This suggests that immune memory cells and humoral immune responses may play a crucial role in protecting against re-infection.

 

Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection

 

In summary, these observations provide mechanistic insights into monkeypox pathogenesis and immunity. Moreover, this study demonstrates the utility of non-human primate models for evaluating monkeypox vaccines and treatments.

Paper link:

 

 

Infection with Monkeypox Virus Induces Natural Immunity to Prevent Re-Infection

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