AUTHOR=Alrasheed Abdullah R. , Awadalla Maaweya , Alnajran Hadeel , Alammash Mohammed H. , Almaqati Adil M. , Qadri Ishtiaq , Alosaimi Bandar TITLE=Harnessing immunotherapeutic molecules and diagnostic biomarkers as human-derived adjuvants for MERS-CoV vaccine development JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1538301 DOI=10.3389/fimmu.2025.1538301 ISSN=1664-3224 ABSTRACT=The pandemic potential of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) highlights the critical need for effective vaccines due to its high fatality rate of around 36%. In this review, we identified a variety of immunotherapeutic molecules and diagnostic biomarkers that could be used in MERS vaccine development as human-derived adjuvants. We identified immune molecules that have been incorporated into standard clinical diagnostics such as CXCL10/IP10, CXCL8/IL-8, CCL5/RANTES, IL-6, and the complement proteins Ca3 and Ca5. Utilization of different human monoclonal antibodies in the treatment of MERS-CoV patients demonstrates promising outcomes in combatting MERS-CoV infections in vivo, such as hMS-1, 4C2H, 3B11-N, NBMS10-FC, HR2P-M2, SAB-301, M336, LCA60, REGN3051, REGN3048, MCA1, MERs-4, MERs-27, MERs-gd27, and MERs-gd33. Host-derived adjuvants such as CCL28, CCL27, RANTES, TCA3, and GM-CSF have shown significant improvements in immune responses, underscoring their potential to bolster both systemic and mucosal immunity. In conclusion, we believe that host-derived adjuvants like HBD-2, CD40L, and LL-37 offer significant advantages over synthetic options in vaccine development, underscoring the need for clinical trials to validate their efficacy.