Monkeypox virus (MPXV): A Brief account of global spread, epidemiology, virology, clinical features, pathogenesis, and therapeutic interventions.

The largest monkeypox virus (MPXV) outbreak of the 21st century occurred in 2022, which caused epidemics in many countries. According to WHO, physical contact with infected persons, contaminated surfaces, or affected animals might be a source of this virus transmission. A febrile sickness including few symptoms found in MPX disease. Skin rash, lesions, fever, headache, fatigue, and muscle aches symptoms were observed commonly for this disease. Animal and in vitro, studies have shown that the antiviral medications cidofovir and brincidofovir are effective against MPXV. The first-generation vaccinia virus vaccine was developed in 1960, and it helped to protect against MPXV with its side effects. A second-generation vaccination with limitations was launched in 2000. However, the CDC advised vaccinations for risk groups in endemic countries, including positive patients and hospital employees. The JYNNEOS vaccine, administered in 2 doses, also provides protection from MPX. This article presents concisely the most recent findings regarding epidemiology, genomic transmission, signs and symptoms, pathogenesis, diagnosis, and therapeutic interventions for MPXV, which may be helpful to researchers and practitioners. WHO declared that MPX was no longer a global health emergency due to its declining case rate, and a number of countries have reported new incidences. Further research-based investigations must be carried out based on the 2022 outbreak.

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.

Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb. We designed murine breast cancer models by implanting TUBO and TUBO-P2J cell lines in mice, which were then treated with anti-HER2/neu and/or anti-4-1BB mAb. After complete surgical and/or chemical regression of the tumor, the mice were rechallenged with a second injection of cancer cells. Notably, anti-HER2/neu and anti-4-1BB mAb combination therapy had a synergistic antitumor effect at the initial treatment. However, the combination therapy did not evoke immune memory, allowing the tumors to thrive at rechallenge with reduced CD44+ expression in CD8+ T cells. Immune memory was also impaired when anti-4-1BB mAb was administered to naive CD8+ T cells but was sustained when this was administered to activated CD8+ T cells. In an attempt to resist the loss of immune memory, we controlled the dose of anti-4-1BB mAb to optimize the stimulation of activated CD8+ T cells. Immune memory was achieved with the dose regulation of anti-4-1BB mAb to 1 mg/kg in our model. Our study demonstrates the importance in understanding the adaptive immune mechanism of anti-HER2/neu and anti-4-1BB mAb combination therapy and suggests a dose optimization strategy is necessary to ensure development of successful immune memory.