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

Yokomizo, Shinya; Katagiri, Wataru; Maki, Yohei; Sano, Tomoya; Inoue, Kazuaki; Fukushi, Masahiro; Atochin, Dmitriy N.; Kubota, Toshihiro; Kawana, Akihiko; Kimizuka, Yoshifumi; Kashiwagi, Satoshi

doi:10.1515/nanoph-2021-0133

Cited by 11 publications

(8 citation statements)

References 89 publications

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“…Examination of antibody titers using the influenza vaccine mouse model showed that IgG antibody titers in the 1270 nm laser group tended to be higher on day 21 than in the ID only group and were significantly higher on day 56. However, similar to our previous report ( 41 ), the 1064 nm laser group in the present study elicited an early antibody production response at day 21. Interestingly, a similar trend was observed during the entire observation period from day 7 to day 112 ( Figure S1 ).…”

Section: Discussionsupporting

confidence: 92%

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

et al. 2022

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With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as “laser adjuvant.” We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as Ccl2 and Ccl20, were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of Nfkb1 was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.

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Section: Discussionsupporting

confidence: 92%

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

et al. 2022

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“…Laser adjuvants deliver non-invasive laser beams to increase motility of antigen-presenting cells (APCs) or microfractional laser beams to create microthermal damages to enhance ID vaccine-induced immune responses. [33][34][35][36][37] Laser adjuvants demonstrated substantial adjuvant effects against seasonal influenza vaccination in preclinical animal models. [33][34][35][36][37] A near-infrared laser adjuvant has advanced to a pilot clinical test and was found to promote cutaneous immune cell trafficking without skin damage.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35][36][37] Laser adjuvants demonstrated substantial adjuvant effects against seasonal influenza vaccination in preclinical animal models. [33][34][35][36][37] A near-infrared laser adjuvant has advanced to a pilot clinical test and was found to promote cutaneous immune cell trafficking without skin damage. 38 Recently, we also reported an ablative fractional laser technology capable of alerting innate immune systems for more immunogenic vaccination without needle injection.…”

Section: Discussionmentioning

confidence: 99%

“…Besides RFA, laser adjuvants have also been explored to boost influenza vaccination with similar advantages as RFA. Laser adjuvants deliver non‐invasive laser beams to increase motility of antigen‐presenting cells (APCs) or micro‐fractional laser beams to create microthermal damages to enhance ID vaccine‐induced immune responses 33–37 . Laser adjuvants demonstrated substantial adjuvant effects against seasonal influenza vaccination in preclinical animal models 33–37 .…”

Section: Discussionmentioning

confidence: 99%

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Physical radiofrequency adjuvant enhances immune responses to influenza H5N1 vaccination

Kim

Bhatnagar

et al. 2022

The FASEB Journal

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Pre‐pandemic influenza H5N1 vaccine has relatively low immunogenicity and often requires high antigen amounts and two immunizations to induce protective immunity. Incorporation of vaccine adjuvants is promising to stretch vaccine doses during pandemic outbreaks. This study presents a physical radiofrequency (RF) adjuvant (RFA) to conveniently and effectively increase the immunogenicity and efficacy of H5N1 vaccine without modification of vaccine preparation. Physical RFA is based on a brief RF treatment of the skin to induce thermal stress to enhance intradermal vaccine‐induced immune responses with minimal local or systemic adverse reactions. We found that physical RFA could significantly increase H5N1 vaccine‐induced hemagglutination inhibition antibody titers in murine models. Intradermal H5N1 vaccine in the presence of RFA but not vaccine alone significantly lowered lung viral titers, reduced body weight loss, and improved survival rates after lethal viral challenges. The improved protection in the presence of RFA was correlated with enhanced humoral and cellular immune responses to H5N1 vaccination in both male and female mice, indicating no gender difference of RFA effects in murine models. Our data support further development of the physical RFA to conveniently enhance the efficacy of H5N1 vaccine.

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“…In contrast to systemic steroids which broadly suppress the immune response, PBM stimulates complexes of the mitochondrial respiratory chain to optimize and modulate the immune response, resulting in an improvement of its ability to eradicate infection via stimulation of the innate and adaptive immune cells [ 44 , 45 , 46 ], while providing an inhibitory effect on excessive inflammation [ 3 ]. Moreover, PBM can prompt cellular regeneration in every organ [ 47 , 48 , 49 , 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up

et al. 2022

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Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 virus was first recognized in late 2019 and remains a significant threat. We therefore assessed the use of local methylene blue photodynamic viral inactivation (MB-PDI) in the oral and nasal cavities, in combination with the systemic anti-viral, anti-inflammatory and antioxidant actions of orally ingested methylene blue (MB) and photobiomodulation (PBM) for COVID-19 disease. The proposed protocol leverages the separate and combined effects of MB and 660nm red light emitted diode (LED) to comprehensively address the pathophysiological sequelae of COVID-19. A total of eight pilot subjects with COVID-19 disease were treated in the Bahamas over the period June 2021–August 2021, using a remote care program that was developed for this purpose. Although not a pre-requisite for inclusion, none of the subjects had received any COVID-19 vaccination prior to commencing the study. Clinical outcome assessment tools included serial cycle threshold measurements as a surrogate estimate of viral load; serial online questionnaires to document symptom response and adverse effects; and a one-year follow-up survey to assess long-term outcomes. All subjects received MB-PDI to target the main sites of viral entry in the nose and mouth. This was the central component of the treatment protocol with the addition of orally ingested MB and/or PBM based on clinical requirements. The mucosal surfaces were irradiated with 660 nm LED in a continuous emission mode at energy density of 49 J/cm2 for PDI and 4.9 J/cm2 for PBM. Although our pilot subjects had significant co-morbidities, extremely high viral loads and moderately severe symptoms during the Delta phase of the pandemic, the response to treatment was highly encouraging. Rapid reductions in viral loads were observed and negative PCR tests were documented within a median of 4 days. These laboratory findings occurred in parallel with significant clinical improvement, mostly within 12–24 h of commencing the treatment protocol. There were no significant adverse effects and none of the subjects who completed the protocol required in-patient hospitalization. The outcomes were similarly encouraging at one-year follow-up with virtual absence of “long COVID” symptoms or of COVID-19 re-infection. Our results indicate that the protocols may be a safe and promising approach to challenging COVID-19 disease. Moreover, due its broad spectrum of activity, this approach has the potential to address the prevailing and future COVID-19 variants and other infections transmitted via the upper respiratory tract. Extensive studies with a large cohort are warranted to validate our results.

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

Cited by 11 publications

References 89 publications

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines

Physical radiofrequency adjuvant enhances immune responses to influenza H5N1 vaccination

A Novel Approach of Combining Methylene Blue Photodynamic Inactivation, Photobiomodulation and Oral Ingested Methylene Blue in COVID-19 Management: A Pilot Clinical Study with 12-Month Follow-Up

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