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Collaborating to accelerate a novel vaccine approach
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Satoshi Kashiwagi, MD, PhD, a principal investigator at the Vaccine and Immunotherapy Center at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, is leading a research effort to develop a new class of vaccine adjuvant. His team recently discovered that pretreating the site of skin vaccination with an invisible near-infrared laser light improves vaccine effectiveness without any adverse effects in a mouse model. Kashiwagi is currently working with Thomas Voss, PhD, executive director and section head of discovery biology at SRI International, with the aim of bringing this research to the clinic. In this guest commentary, Kashiwagi discusses the collaboration and their novel approach to vaccines.
While current vaccines are designed to be safe, their ability to produce an immune response is not strong enough. Many modern vaccines therefore contain immunologic adjuvants, which are chemical or biological additives that stimulate the immune response. However, because adjuvants are designed to produce strong inflammatory reactions in tissues, they may be responsible for many vaccine-associated adverse events. Very few adjuvanted influenza vaccines have received FDA approval. This is in part due to the fact that adjuvants currently in use or in development may cause unexpected side effects.
My team is currently investigating the mechanisms of action of the near-infrared (NIR) laser adjuvant, supported by grants from the NIH and the Friends of VIC Fund. We have shown that nontissue damaging, low-power NIR laser light given in 1-minute increments to small areas of the skin (a spot of 5 mm in diameter) increases the immune responses to influenza vaccine in mice. The laser reduces potential adjuvant toxicity because it does not persist in exposed tissues to induce a prolonged inflammatory cytokine response. To further optimize this technology, we are elucidating cellular and molecular mechanisms of action of the NIR laser adjuvant mainly using a mouse model of influenza vaccination. This project ultimately aims to move this laser technology to an advanced preclinical development stage. The translatability of this discovery is enhanced by the current availability of mature, safe, compact and relatively simple low-wattage continuous-wave NIR laser technology, making it possible to produce a portable, low-cost device. Our 2013 study in PLoS One also shows that this approach is safe in humans, indicating that laser treatment can be considered a safe and effective alternative to conventional adjuvants.
Researchers are using invisible near-infrared laser light technology to improve vaccine effectiveness while minimizing adverse effects.
Source: Satoshi Kashiwagi, MD, PhD
The path forward for vaccine or adjuvant development is long and difficult. It may take 10 to 15 years to satisfy the various regulatory requirements required of a vaccine that will be administered to healthy populations, especially young children. Our team chose an influenza vaccine platform to test the efficacy of the NIR laser adjuvant, aiming at rapid translation of this technology, given that intradermal influenza vaccines are now in use in more than 40 countries, including the United States. The field of influenza vaccine development and licensure process is well-established by regulatory authorities.
Hemagglutination inhibition (HAI) assay has been used for assessing the immunogenicity of influenza vaccines in support of license approval for many decades. This means that the HAI assay has been considered a “gold standard” serologic test to quantitate anti-influenza antibodies in animals and humans. The HAI assay is relatively straightforward and inexpensive to perform and has been correlated with protective immunity in humans. However, at the same time, the process easily can go wrong since the actual results of HAI assay are dependent on subjective reading, and this can be affected by many variables, including freshness of reagents or even the provider of consumable supplies. Studies have shown that there is considerably large variation in the results of HAI assays across laboratories. For such a critical assay, establishment of a rigorous assay system following the standard operating procedures is a key element for further preclinical and clinical vaccine testing.
For researchers like us who are based at an academic institute, establishing a platform — formulating assay protocol, optimizing all the reagents and equipment, and training personnel — is generally not feasible due to the need for excessive resources and time. Early on, we agreed that it would be necessary to identify a partner who could manage this component of the project for us, and we began a search for a group with the right capabilities. Since January, we have collaborated effectively with Voss’ team at SRI International, an organization that has a long-standing reputation in this area. Their immunological and virological assay performance has been confirmed as reproducible by many academic researchers and industrial partners. We send the serum samples obtained in our MGH laboratory to the Voss laboratory at SRI for HAI testing. Their team then performs all of the assays in a blind way for a reasonable cost.
This form of “mutual strength” collaboration will be increasingly important to confirm the reproducibility of results from academic laboratories and further support clinical adjuvant development. In the effort to push this project forward, we need to establish further partnerships with academic and/or corporative entities. These parties perform their own independent review of our data. Because SRI International is recognized by these reviewers, and our study is performed in a blind way, our influenza vaccine efficacy data with HAI titration results have been well-received. Recently, we initiated a new program under partnership with Veralase (a laser company) and Ted Ross, PhD, professor of infectious diseases and director of the Center for Vaccines and Immunology at the University of Georgia, to develop a portable laser adjuvant device. This partnership just received major support from the NIH through the Small Business Technology Transfer award, totaling $1.4 million over 2 years. In short, the MGH-SRI collaboration can be viewed as an example of academia-industry collaboration enabling and accelerating development of promising new vaccine approaches.
References:
FDA. Guidance for Industry. Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines. 2007. http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm091990.pdf. Accessed October 4, 2016.
Kashiwagi S, et al. PLoS One. 2013;doi:10.1371/journal.pone.0082899.
Wagner R, et al. Vaccine. 2012;doi:10.1016/j.vaccine.2012.02.077.
Wood JM, et al. Vaccine. 2012;doi:10.1016/j.vaccine.2011.11.019.
Disclosure: Kashiwagi reports no relevant financial disclosures.