Gelfand JA, N. R., Kashiwagi S, Brauns T, Martin B, Kimizuka Y , Botvinick E , Elkins K, Thomas L, Loscascio J, Parry B, Kelly KM, Poznansky MC (2019). "A Pilot Clinical Trial of a Near–Infrared Laser Vaccine Adjuvant: Safety, Tolerability, and Cutaneous Immune Cell Trafficking." FASEB Journal 33(2) (Full Paper Link)
Kimizuka Y, K. W., Locascio JJ, Shigeta A, Shibata M, Morse K, Reeves P, Suematsu M, Gelfand J, Brauns T, Poznansky MC, Tsukada K, Kashiwagi S. "Brief exposures of skin to near-infrared light modulates mast cell function and augments the immune response." Journal of Immunology 201 (12) 3587-3603 (Full Paper Link)
Kimizuka Y et al. “Semiconductor diode laser device adjuvanting intradermal vaccine.” (2017) Vaccine 35(18) 2404-2412 (Full Paper Link)
Kaitlyn Morse et al. “Near-Infrared 1064 nm Laser Modulates Migratory Dendritic Cells To Augment the Immune Response to Intradermal Influenza Vaccine” (2017) The Journal of Immunology 199:1319-1332 (Full Paper Link)
Kashiwagi, S., T. Brauns and M. C. Poznansky (2016). "Classification of Laser Vaccine Adjuvants." Journal of Vaccines & vaccination 7(1). (Full Paper Link)
Kashiwagi, S., T. Brauns, J. Gelfand and M. C. Poznansky (2014). "Laser vaccine adjuvants: History, progress, and potential." Human Vaccines & Immunotherapeutics 10(7): 1892-1907. (Full Paper Link)
Kashiwagi, S., J. Yuan, B. Forbes, M. L. Hibert, E. L. Lee, L. Whicher, C. Goudie, Y. Yang, T. Chen and B. Edelblute (2013). "Near-infrared laser adjuvant for influenza vaccine." PloS one 8(12): e82899. (Full Paper Link)
Case Study - Veralase Teams Up with MGH to Develop New R&D Lasers
Veralase has established a collaboration with Dr. Satoshi Kashiwagi (click here for detailed biosketch) of the Vaccine and Immunotherapy Center (VIC) at the Massachusetts General Hospital (MGH) to develop small, hand-held diode lasers to support his research. Dr. Kashiwagi discovered that treatment of the skin with certain infrared lasers enhances immune responses to vaccines. The result of this collaboration is a line of small laser devices suitable for research and clinical use that are available through our web site (www.veralase.com).
The Kashiwagi studies in mice have shown that near-infrared (NIR) laser treatment of the skin immediately before vaccination can increase immune responses to and protection against influenza as well as some currently-approved chemical adjuvants. These findings were published in the open-access journal PLOS One (link). As an adjuvant, NIR lasers have the benefit of avoiding the side effects seen frequently with chemical adjuvants, such as inflammation and tissue damage.
Challenges of Laser Vaccine Adjuvants
The initial types of lasers explored as a means of adjuvanting vaccines face critical barriers to further development (http://www.tandfonline.com/doi/full/10.4161/hv.28840). Some types emit in the visible light spectrum where skin absorption will be highly variable depending on skin pigmentation, which might alter the stimulation of immune responses in people with different skin phototypes or pigmentation patterns. This is an important factor in the U.S. where recipients of vaccines represent a broad range of skin phototypes. Some of these lasers also utilize prolonged, ultrashort, high-power pulses that will make production of economic devices for vaccine enhancement challenging.
In his study, Kashiwagi and his colleagues showed that treatment of mouse skin for one minute with a low power (1 Watt), non-pulsed 1064 nm diode laser could evoke vaccine immune responses in a lethal challenge murine influenza model that were superior to those induced by pulsed, visible-light systems described in other studies. These types of diode lasers are far more economical, simple, and robust, making them more ideal for use with vaccines. In addition, using lasers in the near infrared range avoids the high variability of skin absorption due to skin pigementation. This also greatly reduces unwanted thermal effects.
The use of simple and inexpensive diode devices also address what up to now has been a key obstacle to wider testing of this adjuvanting approach: device cost. “To reach the clinic, the technology first needs to be more widely assessed by laboratories studying vaccines for other diseases,” said Dr. Kashiwagi. “Up to now, the lasers used to produce enhanced immune responses to vaccines have been large and expensive laboratory systems that require special technical management.” Scientists who develop vaccines are not typically laser experts or have ready access to technical assistance in this area. These factors together have greatly limited dissemination of this technology.
A New Product is Born
This picture changed in 2014 when the National Institutes of Health (NIH) awarded the collaborative team a grant to test the development of small laser prototypes that could allow a much greater community of investigators to test infrared lasers as adjuvants. As a result of these studies, Veralase is now able to produce a range of infrared, diode-based laser devices for testing a range of potential clinical applications. Veralase continues to work in conjunction with VIC to tune these laser devices to meet the necessary optical parameters required for Dr. Kashiwagi’s studies.
The NIH grant also allowed Veralase to develop software that simplifies control over the laser using a computer, tablet or smart phone. “We developed a laser system that is easy for scientists to program, use and advance scientist research and development of wide-ranging medical treatments,” said David Bean, President of Veralase. “We are excited to develop tools that help scientists make advances in health care. The creation of inexpensive devices that can do the same job as more expensive lasers is at the heart of what our company does.”
During the project, SemiNex Corporation (www.seminex.com) designed new, portable laser engines for the devices while Veralase developed new control boards that could accommodate greater operational flexibility within the R&D environment. A web-based user interface was added to make it easy to program the handheld units and monitor testing progress without any technical background. The interface provides a history of test parameters, dates the device is used and a record of the subjects treated. For clinical applications, a plastic housing was constructed for the device that incorporates the laser engine, control board, rechargeable battery, USB interface and remote operation connection into a compact, handheld unit (Figure 1).
Figure 1: Final assembly of handheld
The Next Steps
The next step in Veralase’s collaboration with Dr. Kashiwagi is to bring a new adjuvant device for intradermal vaccination—a small, near-infrared laser that will emit a brief, non-damaging, non-painful light dose to a small area of skin—to the point of advanced preclinical development. Veralase will keep leading the next steps for system development in support of MGH vaccine applications. In addition, it now offers the handheld technology developed in collaboration with MGH for broader medical research and development purposes. The Veralase laser system is a new tool for medical researchers that is accurate, flexible, portable and cost-effective.