Category Laser type Wavelength Target Spot Size Pulse Duration Pulse Frequency Pulse Energy Average Power Exposure Duration Putative Mechanisms of action Tested in References Conterminal Ultra-short pulsed (UPLVAs) Copper vapor 511/578 nm 5-10 mm in diameter 10-25 ns 5 - 20 kHz 60 μJ 1 - 6 W/cm2 1-3 min Extracellular release of HSP70 to enhance APC activation and antigen presentation Mice, humans [22,23] Q switched Nd:YAG 532 nm 7 mm in diameter 6-7 ns 10 Hz 30 mJ 0.78 W/cm2 1-4 min Derangement of connective tissue facilitates migration of APCs Mice [21,24,25] Q switched Nd:YVO4 532 or 1064 nm 5 mm in diameter 7 ns 10 kHz 67 μJ 1 - 5 W/cm2 1-4 min Photochemical, photothermal and photoacoustic stimulation of tissue leading to APCs activation and migration Mice [26] modelocked Ti:Al2O3 780 nm 0.5 μm 200 fs 76 MHz n.d. n.d. 2 min Membrane permeabilization effects Mice [31] Nonpulsed (NPLVAs) CW Nd:YVO4 1064 nm 5 mm in diameter N/A N/A N/A 5 W/cm2 1-4 min Photochemical reaction in skin tissue leading to immunostimulatory microenvironment for APCs Mice [26] Fractional Nonablative (NAFLVA s) Fractional ER:Glass 1410 nm 7 x 10 mm 10 ms 15.4 Hz 15 mJ n.d. 1-2 sec Sterile inflammation caused by an array of MTZs in skin recruit and activate DCs Mice, pigs [33,34] Ablative (AFLVAs) Fractional ER:YAG 2940 nm 14 mm2 75 μs 200 Hz n.d. n.d. Several seconds The mild inflammatory milieu created in the dermis by skin laser microporation itself activates APCs Mice [37] Nd:YVO4, neodymium-doped yttrium orthovanadate; Nd:YAG, neodymium-doped yttrium aluminum garnet; ER:YAG, erbium:yttrium-aluminium-garnet; CW, continuous wave; microthermal zone, MTZ; APC, antigen presenting cell; DC, dendritic cell; n.d., Not described.

Table 1: Here we review these four major classes and discuss their similarity and distinctiveness as vaccine adjuvants.