Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine

Abstract

Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. Here we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations. We found that a continuous wave (CW) NIR laser adjuvant broadly modulates migratory DC populations, specifically increasing and activating the Lang+ and CD11b−Lang− subsets in skin, and that the antibody responses augmented by the CW NIR laser are dependent on DC subsets expressing CCR2 and Langerin. In comparison, a pulsed wave (PW) NIR laser adjuvant showed limited effects on the migratory DC subsets. Our vaccination study demonstrated that the efficacy of CW NIR laser is significantly better than that of PW laser, indicating that the CW NIR laser offers a desirable immunostimulatory microenvironment for migratory DCs. These results demonstrate the unique ability of the NIR laser adjuvant to selectively target specific migratory DC populations in skin depending on its parameters, and highlight the importance of optimization of laser parameters for desirable immune protection induced by a NIR laser-adjuvanted vaccine.

Laser adjuvant for vaccination

“…It should be noted that the representative adjuvant including alum and MF59, but no laser adjuvant induced allergenic IgE response to the vaccination. Morse et al further demonstrated that the same 1064 nm laser adjuvant modulated migratory DCs in the skin, specifically activating the Lang + and CD11b − Lang − subsets and recruited Ly6C + monocytes . Consistently, and the adjuvant effect was dependent on DC subsets expressing Langerin and CCR2.…”

“…High‐frequency UPL induces HSP70 release, while lower frequency UPL creates disarray of the extracellular matrix, but like other adjuvants used in licensed vaccines, both eventually activate key Langerhans cells and APCs in skin . On the other hand, NPL adjuvant induces ROS generation and activation of innate programs including upregulation of a selective set of chemokines, which were not seen in UPL adjuvant, ultimately activating migratory DCs . In contrast to the AFP or NAFL adjuvant, no tissue damage has been detected by histological examination after the UPL or NPL treatment in the human and mouse skin .…”

A pilot clinical trial of a near‐infrared laser vaccine adjuvant: safety, tolerability, and cutaneous immune cell trafficking

“…Efforts in the United States have iterated this technology from expensive, bulky, poorly scalable lasers (2,11,(14)(15)(16) to diode laser prototypes, which are much less expensive to produce and are more clinically practical. For the same reasons, CW lasers have been chosen over pulsed lasers to reduce device complexity and thus reduce cost from tens of thousands to potentially ,$1000 (9,10,17,18). Current lasers are used with nonpainful, nondamaging energy doses and have been carefully controlled in mouse and human studies to ensure surface temperatures below 43°C, which is the generally accepted thermal pain threshold in the skin (8,19,20).…”

“…Activation and migration of these critical antigen-presenting cells (APCs) enabled immune amplification and dramatically increased protection from lethal viral challenge in several studies of a murine model of i.d. influenza vaccination followed by live virus respiratory influenza challenge (9,17,18). In additional studies (18), relative gene expression of inflammatory cytokines and chemokines in the skin were also measured.…”

“…influenza vaccination followed by live virus respiratory influenza challenge (9,17,18). In additional studies (18), relative gene expression of inflammatory cytokines and chemokines in the skin were also measured. Significant changes in chemokines and immune activators were noted, particularly CCL20, CCL2, CCL11, CCL17, and CCR7, which are all known to affect DC migration and lymphocyte activation, whereas no significant change was noted in TNF-a expression in laser treated mouse skin.…”