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Mucosal Vaccines against Viruses

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Mucosal surfaces are among the primary and most vulnerable areas of our body when it comes to viral entry and infection. The Iwasaki Lab hopes to present new ways to administer vaccines that confer certain protective advantages over conventional methods. Below are two such mechanisms, studied in the context of the herpes virus and COVID-19 virus, respectively. We are currently developing other innovative vaccine approaches.

Prime and Pull:

Effective recruitment of immune cells to sites of viral infection is critical for treatment and recovery from various diseases, but our body’s natural response in doing so can be compromised for a number of reasons. Organs such as the intestines and lung airways — as well as the human vaginal tract, for instance, often restrict T-cell entry unless in the case of inflammation. Understanding that many current therapeutics have difficulty circumventing this barrier, the Iwasaki Lab has helped develop a mechanism called “prime and pull,” which has shown significant promise in both reducing the spread of infection and preventing recurrent symptoms caused by mucosal viruses.

There are two main steps to the method: first, a conventional intramuscular vaccination is administered to “prime” and initiate systemic T-cell response. Next, a cream containing medication that “pulls” T-cells to the site of viral growth is applied on or under the skin; this establishes an existing pool of protective memory T-cells within peripheral tissue where T-cell travel and entry might naturally be restricted. Prior research has demonstrated that tissue-resident memory T-cells are much more efficacious than circulating memory T-cells, partially because of their locality.

The Iwasaki Lab tested the “prime and pull” method on guinea pigs already infected with the herpes simplex virus to examine its efficacy in preventing recurrent herpes lesions. In one group, individuals were given both a traditional vaccine and a cream that had imiquimod, a substance commonly used to treat skin tumors, warts, and which increases the activity of the immune system. The results supported the team’s hypotheses: a combination of priming and pulling exceeded the efficiency of the vaccine or cream alone, reducing the ability of the HSV-2 to reactivate from latency in sensory neurons. But the good news didn’t just end there. Priming and pulling also blocked blisters from forming when administered to guinea pigs with recurrent herpes disease — suggesting a potential solution to controlling disease course in an individual.

Researchers in the lab are hopeful that the new mechanism will chart future development in the fight against mucosal viral diseases, and look forward to conversations with biotechnology and pharma companies on taking advantage of this combination vaccine strategy to improve outcomes for patients.

Prime and Spike:

The COVID-19 pandemic has sent medical communities around the world into an arms race of vaccine development; dose after dose and booster after another, our research co-evolves with the virus, which persistently adapts to become transmissible.

The Iwasaki lab presents a new mechanism of administering booster shots that might turn tables in our struggle against this global pandemic: priming and spiking. After receiving traditional mRNA-based vaccines, patients would receive reinforcement delivered directly to their nose, which contains and leads to the parts of the body most affected by viral infection. The second step would come in the form of a spray containing coronavirus-derived spike proteins — and in some cases, a non-inflammable and biodegradable polymer coat.

Conventional intramuscular boosters, the type most popular today, unfortunately show diminished ability to fight the virus over time — and also lack efficiency in the mucosa of the vulnerable nasal cavity and respiratory tract. On the other hand, the prime and spike mechanism induces a robust population of tissue-resident memory T-cells, B-cells, and immunoglobulin A directly in the respiratory mucosa, strengthening the body’s systemic prevention of viral entry and offering cross-reactive, cross-protective immunity.

Researchers at the Iwasaki Lab developed this method after drawing inspiration from their work with the influenza virus. For both illnesses, infected individuals who received priming and pulling had less viral load in their nasal cavity and lungs, affirming the reduced viral infection and transmission made possible by the treatment.

Prime and Spike technology forms the scientific basis for Xanadu Bio.