Evaluation of the Effectiveness and Safety of the LC16m8 Mpox Vaccine in Individuals Aged One Year and Older in the Democratic Republic of Congo (DRC)

1. Community Engagement: The community mobilization will be carried out according to the national communication plan for the vaccination promotion. Study staff members will engage with religious leaders, medical professionals, heads of villages, and key opinion leaders to share information about the mpox disease surveillance, the availability of the vaccine, and the vaccination. Additionally, detailed information regarding the available mpox testing and treatment facilities that the community needs to visit if any person develops symptoms consistent with mpox or develops adverse events following vaccination will be provided in the community engagement activities. Special emphasis will be made in the community messaging to encourage all individuals with mpox-compatible symptoms regardless of the disease severity and vaccination status-to promptly seek testing and care.
2. Enhanced Health Facility-based Mpox Disease Surveillance: Health facility-based and enhanced mpox surveillance will be implemented to record mpox cases within the vaccination catchment area. The study will be done in 2 or more health zones identified as hot spots by the DRC government.

The healthcare facilities within the study catchment area will be equipped with mpox testing equipment & supplies and the study staff will receive comprehensive training for the mpox case investigation, sample collection, and management. Pre-existing laboratories will be supported by the project to perform RT-PCR tests, and a subset of samples will be shipped to the reference microbiology laboratory at INRB headquarters in Kinshasa for quality control.

Patients presenting at a sentinel surveillance healthcare facility with suspected or probable mpox will be approached for enrollment. For patients presenting with skin lesions, a swab of the skin will be collected from all suspected/probable mpox cases for testing using RT-PCR. Out of the patients presenting with skin lesions, one hundred patients will be consecutively invited to provide oro-pharyngeal swab and saliva to assess the diagnostic accuracy of other samples compared to skin swab. For patients presenting without skin lesions, oro-pharyngeal swab will be taken. Each suspected case will be asked for contact information (telephone number and/or description of residence). After 3 weeks, study staff will seek to contact, by telephone and/or in-person visit, each suspected case who tested negative by RT-PCR at enrollment to assess whether or not the individual experienced additional symptoms and signs consistent with symptomatic mpox, particularly the development of skin lesions. The study staff will seek to collect skin or oropharyngeal swabs from initially test-negative patients who reported experiencing additional symptoms consistent with symptomatic mpox during the three-week period after enrollment and to test these samples by RT-PCR.

1. Laboratory Procedure: Real-time polymerase chain reaction (RT-PCR) for the presence of MPXV in skin swabs from all patients presenting with skin lesions suggestive of mpox will be performed for laboratory confirmation and diagnosis of mpox. For patients presenting without skin lesions, oro-pharyngeal swab will be tested using RT-PCR. The RT-PCR protocols for the detection of MPXV will be performed according to manufacturer's instructions, in line with WHO guidelines for the detection of MPXV.
2. Specimen Type, Collection, Transport and Storage: Skin lesion material includes swabs of lesion surface and/or exudate, or lesion crusts. Lesions will be swabbed vigorously to ensure adequate viral DNA is collected. Swabs will either be transported dry in capped tubes or placed in viral transport media (VTM). Whenever possible, specimens from two lesions should be collected in one single tube, preferably from different locations on the body. For patients with no skin lesions at presentation, oro-pharyngeal swabs will be taken. Samples will be stored at 2-8°C if processed within 72 hours. Samples that are shipped to reference laboratories will be stored at -20°C or lower. Longer-term storage (>60 days) will be at -70°C. All specimens being transported should have appropriate triple packaging, labelling, and documentation.
3. Vaccination using LC16m8 Vaccine: As the study aims to generate real-world vaccine effectiveness by leveraging DRC's national mpox vaccination strategy, the vaccination will be conducted in 2 or more health zones/areas which meet the criteria for a hotspot as defined by the DRC vaccination strategy for targeted vaccine delivery.

Selection of health zones/area for the study where LC16m8 is expected to be offered to everyone one year or older, will be determined based on the latest mpox epidemiological data, operational feasibility, and existing research infrastructure in close consultation with DRC MoH, Institut National de Santé Publique (INSP), and local stakeholders. Due to on-going mpox outbreaks in multiple provinces in DRC, investigators will also ensure enough doses are allocated and delivered to selected health zones/areas to reach minimum coverage required for the study (i.e., 30% coverage). Details of the vaccination strategy will be determined in close collaboration with local public health authorities.

a. Vaccination Information Registration: As mpox vaccine is being offered as part of DRC's national mpox vaccination strategy, consent/assent procedure for the vaccination will be carried out according to the routine public health immunization program. Vaccination sites/centers will collect mpox vaccination registry as per routine practice as well and provide a vaccination card along with detailed instructions on how to securely retain it for future reference.