Objectives: Understanding the antibody response in monkeypox virus (MPXV)-infected and uninfected individuals is essential for developing next-generation MPXV vaccines. This study aimed to characterize neutralizing antibody (NAb) and antibody-dependent cellular cytotoxicity (ADCC) responses in both groups, providing insights into immune protection and vaccine design. Methods: A recombinant vaccinia Tian Tan (VTT) virus was utilized to develop high-throughput luciferase-reporter-based neutralization and ADCC assays. These assays were applied to evaluate the presence and levels of poxvirus-specific antibodies in MPXV-infected and uninfected individuals, including those vaccinated with vaccinia-based vaccines. Results: Poxvirus-specific NAbs were detected in MPXV-negative individuals with prior vaccinia vaccination. However, MSM individuals exhibited significantly lower pre-existing NAb levels than non-MSM individuals, potentially contributing to their higher susceptibility to MPXV infection. In individuals with mild MPXV infection, robust NAb and ADCC responses were observed, regardless of vaccination status. Additionally, HIV-positive individuals demonstrated comparable antibody responses following MPXV infection. Conclusions: These findings highlight the potential role of pre-existing NAbs in MPXV susceptibility and the strong immune response elicited by mild MPXV infection. Further research is needed to determine whether MPXV-specific antibodies mitigate disease progression, which could inform the development of effective MPXV vaccines.

Introduction: Historically, human infections with clade Ia monkeypox virus (MPXV) primarily occurred through zoonotic transmission with limited secondary human-to-human transmission. Recent studies suggest increasing evidence of human-to-human transmission of some clade Ia lineages. This report documents the first imported clade Ia mpox case in Shanghai, representing the second documented case in China. Methods: Patient demographics, clinical profiles, epidemiological history, and close contacts were obtained through interviews with the patient and attending physicians. Clinical specimens were collected for real-time fluorescent quantitative polymerase chain reaction (qPCR) and whole-genome sequencing. Contact tracing was implemented, involving a 21-day health monitoring of close contacts. Results: The patient presented with moderate symptoms, including fever, rash, and respiratory manifestations. Genome sequencing identified the virus as clade Ia, showing 99.96% nucleotide identity to a strain from the Democratic Republic of Congo (DRC). Eight close contacts were identified with no secondary infection reported. Conclusions: This case was confirmed as an imported clade Ia mpox case originating in the DRC. The “four JOINTs” cross-agency collaborative mechanism between the CDC and customs played a significant role in effectively stopping local transmission. Challenges in remote investigation highlight the need for stronger international collaboration. Establishing an integrated “early warning-control-tracking” system, coupled with public health intervention, is crucial for reducing importation risks and safeguarding national health security.