The majority of pathogens, including HIV, influenza virus and Mycobacterium tuberculosis; that contribute to the global burden of infectious disease initiate infection at the mucosal barrier tissues. At least two subsets of memory CD8+ T cells patrol the mucosal tissues as a front line defence; a non-recirculating, tissue-resident memory (TRM) population of CD8+ T cells; and an effector memory (TEM) population of CD8+ T cells; that circulate between the blood and non-lymphoid tissues. These subsets of CD8+ T cells are uniquely poising to provide an immediate response; within minutes to hours of pathogen detection at the barrier tissues and dictate the outcome of infection.
In a study published today in the Nature Communications, researchers from King’s College London have shown how skin vaccination can generate protective CD8 T-cells that are recruited to the genital tissues and could be used as a vaccination strategy for sexually transmitted infections (STIs).
One of the challenges in developing vaccines for STIs, such as HIV or herpes simplex virus; is understanding how to attract specialized immune cells, called CD8 T-cells; to take up residence in the part of the body where the virus first enters. These cells need to place, arm and ready to provide an immediate protective immune defense; rather than waiting for immune cells in the blood to enter the tissues which takes time.
Specialized immune cells
Before this study, it was vaccines ideally need; to be deliver directly to the body surface (e.g. female genital tissue); where the infection might start, so that the immune system can generate these CD8 T-cells; travel back to the vaccination site and eliminate any future virus that is encounter. However, delivering vaccines directly to the female genital tissue is neither patient friendly nor efficient.
Now the team from King’s have found that their vaccination strategy marshals a platoon of immune cells; called innate lymphoid cells (ILC1) and monocytes, in the genital tissues to work together and release chemicals (chemokines); to send out a call to the CD8 T-cells generated by the vaccine to troop into the genital tissue.
Skin vaccination techniques
This research builds on the team’s earlier work to develop skin vaccination techniques using a dissolvable ‘microneedle’ vaccine; patch that once placed against the skin dissolves and releases the vaccine without requiring a hypodermic needle; injection and generates immune responses.
Lead author, Professor Linda Klavinskis from King’s College London said: This study highlights how specialized groups of ‘innate’ immune cells in distant tissues can be harnessed to attract protective CD8 T-cells, arming the body’s frontline tissues from infection. We now need to confirm these results with other types of vaccines from the one used in the study to see if a common pathway is triggered by skin vaccination. If proven, this could have a significant impact in improving the effectiveness of vaccines against sexually transmitted infections,” said Klavinskis.