August 3, 2014
Influenza imposes a heavy annual public health burden, and lies historically at the heart of a number of global pandemics that killed tens of millions. To overcome the challenges of manufacturing enough vaccines such that we may stave off the next epidemic, medical researchers are searching for ways to strengthen or extend the power of existing and stockpiled vaccines. Now a team of scientists in Boston has just developed a new method of using laser light to stimulate and enhance the immune response to a vaccine by a remarkable 4 to 7-fold against disease agents. Such treatments that assist vaccines but are not vaccines themselves are known as adjuvants.
Interestingly, the improved 4 to 7-fold laser adjuvant could not be matched even when compared against increasing the vaccine dosage 10-fold. Efficacy of the vaccine was measured by the level of influenza-specific antibodies generated in an inoculated person. The new method improves on an existing adjuvant hampered by harmful side effects which thus far has prevented its usage broadly. Although the results were obtained in the context of two animal models, adult and aged mice, as well as pigs, its fairly general immunological basis is expected to translate to humans.
Before inoculation, the injection site is exposed to laser light for a short time. The light does not perforate the outer layers of the skin, but rather injures the dermis. Because of the way the laser light is arranged, this creates a number of “microthermal zones.” In each zone, dermal cells that are damaged stimulate inflammation, signaling danger to the immune system, which in turn attracts antigen-presenting cells (APCs) to the damaged area. APCs are cells that occur naturally in the body that bind antigens of harmful disease agents so as to prepare the rest of the immune system to recognize and neutralize the threat. Each zone is only 200 micrometers by 300 micrometers. Given that there are 54 zones, the total area is less than 2 square millimeters.
The damaged area is so small such that that self-healing occurs within 72 hours. The inspiration for the adjuvant comes from a type of skin treatment used in cosmetic dermatology. In the cosmetic context, the laser light is used to stimulate lightly skin with aged appearance. Post-damage, epithelial cells quickly grow to surround the microthermal zone to give rise to more youthful looking skin. The same class of non-ablative lasers were used in this study.
The researchers, led by first author Dr. Ji Wang and Professor Mei Wu at the Massachusetts General Hospital, and the Harvard-MIT Division of Health Science and Technology, discovered that the process is driven by attraction of plasmacytoid dendritic cells (pDCs), a type of immune cell. The researchers used three methods to block pDCs to verify these cells are essential.
Causing controlled skin injury to enhance the efficacy of the vaccination is called micro-sterile inflammation increase. Other similar preclinical studies have fared worse because of greater damage at the site of application, leading to severely inflamed skin legions. Most importantly the results show increased effectiveness in influenza vaccine.
The studies have important implications for elderly patients, who are more susceptible to opportunistic or idiopathic conditions, i.e. conditions caused by the treatment itself. Since only the vaccine and not the adjuvant needs to be injected, the adjuvant’s efficacy and safety are both increased for the individual. From a public health perspective, the adjuvant is a major boon as it cuts down on the costs and extends the power of existing vaccines, vital steps forward in augmenting our ability to deal with future pandemics.
The research was published in Nature Communications.