H. Tanaka1, S. Yamamoto1, G. Rahal2, Z. Khalil3, A. Abdel-Fattah3, K. Nassar4, Y. El-Hadidy4, T. Sabry4, F. Zaki4, O. Khalil4, L. Barakat3, S. El-Gazzar3, N. El-Shenawy4, R. Sato1, A. Kobayashi1, K. Nakamura1, H. Suzuki5, Y. Ito5, K. Matsuda5, K. Al-Mansoori6, F. Al-Hashmi6, O. Al-Neyadi6, A. Al-Ketbi6, H. Al-Falasi6, S. Al-Mazrouei7, N. Al-Rashid7, B. Al-Qahtani7, L. Al-Harbi7, Z. Al-Otaibi7, Y. Al-Hadid8, R. Al-Abdallat8, S. Al-Khalili8, L. Al-Qudah9, Y. Abi Haidar2, M. Wehbe2, T. Jabbour2, N. El-Khoury2, L. Zoghby2, IAS-2025 group 1NCGM Disease Control & Prevention Center (DCC), Research Department, 1-chōme-21-1 Toyama, Shinjuku City, Tokyo 162-0052, Japan, Japan, 2Center for Infectious Diseases Research (CIDR) at the American University of Beirut Medical Center (AUBMC), Research Department, AUBMC, Department of Pediatrics and Adolescent Medicine, Phase 1, 6th floor, room W616., Lebanon, 3October 6 University, Research Department, Egypt-Cairo, Egypt, 4Al-Azhar University, Research Department, Egypt-Cairo, Egypt, 5National Institute of Infectious Diseases, Toyama Research Office, Research Department, 1-chōme-23-1 Toyama, Shinjuku City, Tokyo 162-0052, Japan, Japan, 6Kalba Hospital, Research Department, Sharjah - Al Saf 8 - Sharjah Emirate - United Arab Emirates, United Arab Emirates, the, 7Riyadh Clinical Simulation Center, Research Department, QV35+J3W, Ar Rimayah, Riyadh 14611, Saudi Arabia., Saudi Arabia, 8Information and Research Center - King Hussein Foundation (IRCKHF), Research Department, 7 Ibrahim Al Bajouri St., Swaifyeh, Amman, Jordan., Jordan, 9Jordan Hospital, Research Department, An-Nuzha St, Amman, Jordan., Jordan
BACKGROUND: Mpox cases have surged across the Middle East since 2023, raising concerns over viral evolution, reduced vaccine protection, and gaps in regional surveillance—particularly for people with HIV. The PROJECT Trial characterized viral adaptation, immunity durability, and outbreak dynamics in five Middle Eastern countries.
METHODS: This prospective, multicenter cohort study enrolled 9,126 individuals (including 687 people with HIV [PWH]) from Saudi Arabia, UAE, Egypt, Jordan, and Lebanon over 18 months. Participants were stratified into: MVA-BN-vaccinated (N=4,573), prior-Mpox-exposed (N=3,129), and unvaccinated/unexposed controls (N=1,424), with HIV status documented for all. Full-length viral sequencing (every 8 weeks) prioritized PWH samples for adaptive mutation analysis. Humoral/cellular immunity (neutralization titers, IFN-? ELISPOT) compared PWH (n=687) vs. non-HIV participants. Transmission modeling weighted HIV-specific risks (e.g., CD4 count <200) alongside contact-tracing and mass-gathering data.
RESULTS:
Clade IV-ME Mpox (41.3% prevalence) carries A27L-L205F mutation enhancing spread. Vaccinated groups showed 64% antibody decline (1:128?1:46; 1:98?1:29 in PWH), with 17.4% breakthrough cases (23.1% in PWH; aHR=2.21). T-cell responses dropped 32% (47% in PWH; p<0.001). R0=1.72 (general) ? 2.48 (mass gatherings), 28.4% linked to PWH super-spreading. Asymptomatic rate: 13.6% (6.3% in PWH). Hospitalizations 1.9× higher overall (3.2× in PWH). Variant detection delayed 6 weeks (22% PWH undiagnosed pre-hospitalization).
Table 1. Key Findings and Implications of Mpox Clade IV-ME
| Finding | Data | Implication / Clinical Significance |
|---|---|---|
| A27L-L205F mutation | Enhances viral adhesion/entry | Increased the ability to spread may require updated vaccines or therapeutics targeting this mechanism. |
| Neutralizing antibody decline | 64% drop (1:128 ? 1:46) by 12 months post-vaccination | Current vaccines lose efficacy over time; booster doses may be needed for sustained protection. |
| Breakthrough cases | 17.4% rate; aHR 2.21 if vaccinated >10 months prior (95% CI: 1.88–2.59) | Revaccination schedules should prioritize high-risk groups (e.g., immunocompromised, sexual health clinics). |
| T-cell response reduction | 32% lower vs. Clade II (p=0.003) | Cellular immunity is compromised; vaccines may need adjuvants to enhance T-cell activation. |
| Increased transmissibility (R0) | R0=1.72 (baseline) ? 2.48 (mass gatherings) | Targeted interventions (e.g., pre-event vaccination, testing) critical for concerts/festivals. |
| Asymptomatic transmission | 13.6% of secondary cases | Silent spread complicates containment; contact tracing and PCR screening must be prioritized. |
| Higher hospitalization in vaccinated | 1.9× higher vs. unvaccinated (Egypt/Jordan) | Breakthrough cases may present atypically; clinicians need training to recognize Clade IV-ME symptoms. |
| Delayed variant detection | Up to 6-week lag in Lebanon/Jordan | Investment in regional genomic surveillance is urgent to track emerging variants. |
| Domain | Virologic Feature | Population Impact | Countermeasure Gap |
|---|---|---|---|
| The ability to spread | • A27L-L205F mutation (? adhesion) | • R0=1.72?2.48 in mass gatherings | • Current vaccines target ancestral strains |
| Immune Escape | • 32% ? T-cell response (p=0.003) | • 17.4% breakthrough cases (aHR=2.21*) | • No clade-specific boosters available |
| Transmission | • 13.6% asymptomatic transmission | • 6-week variant detection delays in Levant | • Limited PCR screening capacity |
| Clinical | • 1.9× ? hospitalization (vax vs unvax) | • Atypical symptoms delay diagnosis | • Clinician training outdated |