Laser adjuvant for vaccination

Abstract

The use of an immunologic adjuvant to augment the immune response is essential for modern vaccines which are relatively ineffective on their own. In the past decade, researchers have been consistently reporting that skin treatment with a physical parameter, namely laser light, augments the immune response to vaccine and functions as an immunologic adjuvant. This “laser adjuvant” has numerous advantages over the conventional chemical or biological agents; it is free from cold chain storage, hypodermic needles, biohazardous sharp waste, irreversible formulation with vaccine antigen, undesirable biodistribution in vital organs, or unknown long‐term toxicity. Since vaccine formulations are given to healthy populations, these characteristics render the “laser adjuvant” significant advantages for clinical use and open a new developmental path for a safe and effective vaccine. In addition, laser technology has been used in the clinic for more than three decades and is therefore technically matured and has been proved to be safe. Currently, four classes of laser adjuvant have been reported; ultrashort pulsed, non‐pulsed, non‐ablative fractional, and ablative fractional lasers. Since each class of the laser adjuvant shows a distinct mechanism of action, a proper choice is necessary to craft an effective vaccine formulation toward a desired clinical benefit for a clinical vaccine to maximize protection. In addition, data also suggest that further improvement in the efficacy is possible when a laser adjuvant is combined with chemical or biological adjuvant(s). To realize these goals, further efforts to uncover the molecular mechanisms of action of the laser adjuvants is warranted. This review provides a summary and comments of the recent updates in the laser adjuvant technology.

Brief exposure of skin to near-infrared laser augments early vaccine responses

“…Since prophylactic vaccines need to be broadly administered to healthy subjects, the use of chemicals or biologicals with potential side effects is not desirable in the initial phase of the pandemic when uninfected healthy populations need to be protected in a timely manner. The laser is a physical parameter and with the correct range poses no risk of side effects [ 31 – 33 ]. In order to promptly establish herd immunity with vaccination, the laser-based adjuvant, which safely augments early antibody responses to the vaccine, would be a feasible option for the candidate vaccines in the initial phase of the pandemic.…”

“…Although the use of NIR wavelengths as compared to visual wavelengths pushes effective limit up to a depth of a few millimeters, laser adjuvant is not compatible with most of the modern vaccines, which are administered via the standard intramuscular or subcutaneous routes [ 31 , 32 ], posing unique technical challenges to this modality. Interestingly, laser adjuvant has been shown to augment humoral and antigen-specific CD4 + and CD8 + T cell responses to intramuscular immunization in a mouse model using a hair-like optical fiber [ 73 ], suggesting that laser adjuvant has the potential to augment the immune response to intramuscular vaccines.…”

“…In the past decade, researchers have consistently reported that skin treatment with near-infrared (NIR) laser activates innate immunity and augments the immune response to the vaccine [ 31 – 33 ]. Currently, four classes of laser adjuvants have been established; ultra-short pulsed [ 34 ], nonpulsed [ 34 – 38 ], nonablative fractional [ 39 – 43 ], and ablative fractional [ 44 – 52 ] lasers.…”

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

“…This agreed with previous human trial results on ablative fractional laser pretreatment, showing that thermal ablation was well tolerated, with 12 patients rating thermal ablation 3 on average on a pain scale of 0 to 10. However, pain scores ranged from 1–9 for individual participants [ 187 ]. The technology has continued to progress and a clinical trial (NCT02988739) sponsored by Pantec Biosolutions AG, investigating the utility of the P.L.E.A.S.E.…”

Laser Immunotherapy: A Potential Treatment Modality for Keratinocyte Carcinoma

“…The immune activating feature of lasers is furthermore supported by their potential to act as vaccine adjuvants, recently reviewed for ultrashort pulsed laser, non-pulsed laser, AFL and non-ablative fractional lasers [ 54 ]. The review covers a body of more than 25 publications covering preclinical and clinical studies showing substantial laser-mediated induction of specific antibodies towards vaccine antigens or infiltration of cytotoxic T lymphocytes in tumor [ 55 ] and infection models [ 56 ] with many studies pointing at a synergistic effect of laser and chemical adjuvants.…”