Laser vaccine adjuvants. History, progress, and potential

Abstract

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

Keywords: cancer; influenza; laser; near-infrared; vaccine adjuvant.

Figure 1. Comparison of the typical irradiances and fluences for laser dermatology procedures. A plot of irradiances vs. fluences for dermatologic applications of lasers is shown. Note that parameters of LVA are quite distinct from those of other applications. *Data represents single pulse treatment on a specific skin target.

Figure 2. Putative mechanisms of action of NIR laser adjuvant. Non-tissue damaging continuous wave (CW) near-infrared (NIR) 1064 nm laser given in short exposures to small areas of the skin is able to augment broad immunity including antibody, T_H1 and T_H2 immune responses to vaccination. NIR laser adjuvant stimulates the expression of a defined set of cytokines and chemokines including CCL2 and CCL20 (via undefined molecular mechanisms) that ultimately induce functional and migrational changes in DCs in the skin. Figure courtesy of Eugene L.Q. Lee (Imperial College London).

Figure 3. Absorption spectrum for major skin chromophores and the optical window. Light absorption in the skin is wavelength dependent. In the UV to near infrared portion of the spectrum, the predominant tissue chromophores are hemoglobin, melanin, and water. The absorption coefficients for both melanin and hemoglobin decline significantly after 600 nm and water does not increase significantly until after 1200 nm. This creates an “optical window” at red and near-IR wavelengths that maximizes penetration of light into the skin. Note that the 1064 nm NIR laser adjuvant is within the window whereas 510/578 or 532 nm pulsed laser adjuvants are not. Hb, hemoglobin; HbO2, oxygenated hemoglobin. Figure courtesy of Dr Michael Hamblin (Massachusetts General Hospital).

Figure 4. The distinctions between pulsed and continuous wave laser vaccine adjuvants. There are 2 major types of laser vaccine adjuvant (LVA). Each class of LVA has a distinct mode of laser-tissue interaction, mechanisms of action, and the effect on antigen presenting cells (APCs). NIR, near-infrared; ROS, reactive oxygen species; RNS, reactive nitrogen species; DC, dendritic cell; LNs, lymph nodes.