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. 2025 Sep 29;16:1646800. doi: 10.3389/fimmu.2025.1646800

Table 1.

Molecular adjuvants by class.

Cytokines Antigens Significant Findings Reference
IL-12 Mycobacterium
tuberculosis (Mtb),
SARS-CoV-2, Listeria monocytogenes-OVA
Sustained immunity to SARS-CoV-2 mRNA-LNP, enhances CTL responses Morelli et al. (51)
Brook et al. (44)
Aunins et al. (52)
IL-2 rabbit hemorrhagic disease virus VP60, infectious bursal disease virus, Edwardsiella tarda, infectious laryngotracheitis virus, autoimmune diabetes Enhances T cell proliferation and protection across many animal and disease models Deng et al. (53)
Huo et al. (54)
Tang et al. (55)
Hao et al. (56)
Pagni et al. (57)
IL-4 Influenza hemagglutinin, coccidiosis Combination approaches preserve
Th1-related responses
Wei et al. (58)
Tan et al. (59)
IL-15 SIV-Gag/SIV-Nef,
HPV16 E6/E7
Enhances CTL responses despite delivery constraints regarding trans-presentation Leroy et al. (60)
Zhou et al. (61)
IL-18 genotype VII Newcastle Disease Virus Enhances Th1-related responses in chickens and murine cancer models Wang et al. (62)
Yadav et al. (63)
IL-28B
(IFN-λ3)
H1N1 (inactivated virus vaccine), Newcastle Disease Virus,
HPV16 E6/E7
Promotes robust CD8+ activation by Treg suppression Sabbaghi et al. (64)
Amoia et al. (65)
Zhou et al. (61)
GM-CSF SARS-CoV-2 WT, Omi,
Influenza HA
Enhances germinal center formation Liu et al. (66)
Wei et al. (58)
Chemokines Antigens Significant Findings Reference
CCR10 Ligands (CCL27, CCL28) SARS-CoV-2 WT, BA.2, XBB.1.5, influenza,
HIV-1 env
Drive robust mucosal immunity in murine models of challenge Gary et al. (13)
Gary et al. (67)
Liaw et al. (68)
CCR7 Ligands (CCL19, CCL21) Vibrio anguillarum antigen (VAA), VHSV,
H7N9 HA
Enhance systemic & mucosal immunity across animal models Xu et al. (69)
Kim et al. (70)
Xiang et al. (71)
Co-stimulators Antigens Significant Findings Reference
CD40L autoimmune glomerulonephritis (EAG), SARS-CoV-2, Tembusu virus, bovine herpesvirus 1 (BoHV-1) Potent multi-faceted immune enhancement via dendritic cell activation across animal models Li et al. (72)
Tamming et al. (73)
Huang et al. (74)
Kornuta et al. (75)
CD80/86 Vibrio anguillarum OmpK increased IgM+ and CD4+ populations Liu et al. (76)
Immunomodulators Antigens Significant Findings Reference
Adenosine deaminase HIV-1, SARS-CoV-2 Mitigates age-associated immunosenescence in mouse models Gary et al. (13)
Cusimano et al. (8)
Gary et al. (7)
C3d Porcine Circovirus Type 2 (PCV2) ORF2 , SARS-CoV-2 Significantly increases antibody responses Hou et al. (77)
Li et al. (78)