Location, location, location: Immunization delivery site matters

December 1, 2017, Jackson Laboratory
Credit: National Cancer Institute

In vaccination, a certain subpopulation of dendritic cells is vital to triggering the body's adaptive immune system, report researchers at The Jackson Laboratory (JAX), Yale University and Astra-Zeneca.

Their findings have important implications for vaccine delivery, as the usual method, , is likely not the most effective way to target those dendritic cells.

Vaccines train the immune system to fight a given pathogen (e.g., bacteria or virus), known generally as an antigen, by simulating a natural infection. When an antigen is detected, a dendritic cell, which has the job of processing and transporting antigens, carries it to a lymph node. There it "presents" the antigen to a specialized T cell, known as a T follicular helper (Tfh) cell, activating it. Through signaling the Tfh cells stimulate B cells, which in turn produce antibodies specific to the antigen.

So for a vaccine to work at its best, it needs to be delivered where it's most accessible to dendritic cells. However, there are many different kinds of dendritic cells, and they're not distributed uniformly throughout the body.

In a paper published in Science Immunology, the team, led by senior co-authors JAX Assistant Professor Adam Williams, Ph.D. and Stephanie Eisenbarth, M.D. Ph.D., of Yale, showed that dendritic cells known as cDC2s (for CD11b+ migratory type 2 conventional DCs) are both necessary and sufficient for robust Tfh cell induction. Working with mice that lack a protein needed for cDC2 mobility, the team demonstrated that Tfh cells were not induced and antibodies not produced following vaccination, even in the presence of other, functional dendritic .

The authors used inhalants for their research and show that multiple types of DCs access antigens through this delivery form. In particular, cDC2s deliver inhaled antigens to lung-draining , and there induce a potent Tfh response.

In contrast, the usual method of vaccination through intramuscular injection delivers antigen to where cDC2s are relatively scarce. Based on older epidemiological data and a similar repertoire of cDC2s in the superficial layer of the skin, the researchers speculate that intradermal injections may be far more efficient in driving antibody production.

Moreover, more efficient delivery of vaccines could mean that smaller doses could be administered, expanding the number of people who could be vaccinated during a pandemic or when a given vaccine is in short supply.

Williams notes that the work also underscored the importance of using an animal model system rather than in vitro cell lines. "Not only are dendritic cell types concentrated in different areas of the body, they also migrate to specialized areas within the lymph node. This fundamental aspect of immune architecture is lost in vitro," says Williams. "Having mouse models in which specific were disabled or deleted was essential for this work."

Explore further: How genetically engineered viruses develop into effective vaccines

More information: J.K. Krishnaswamy el al., "Migratory CD11b+ conventional dendritic cells induce T follicular helper cell dependent antibody responses," Science Immunology (2017). immunology.sciencemag.org/look … 6/sciimmunol.aam9169

Related Stories

How genetically engineered viruses develop into effective vaccines

July 26, 2017
Lentiviral vectors are virus particles that can be used as a vaccine to stimulate the immune system to fight against specific pathogens. The vectors are derived from HIV, rendered non-pathogenic, and then engineered to carry ...

TB dogma upended: Even uninfected cells trigger immune defenses

June 11, 2014
Experimenting with mice, infectious disease experts at NYU Langone Medical Center have found that immune system cells uninfected with the bacterium that causes tuberculosis trigger immune system T cells to fight the disease. ...

Understanding the origins and function of CD14+ immune cells

February 4, 2015
Dendritic cells and macrophages are immune cells that orchestrate diverse immune functions within many body tissues, including the skin. New work by A*STAR researchers and colleagues shows that CD14+ cells in the skin—long ...

Skin sentry cells promote distinct immune responses

July 21, 2011
A new study reveals that just as different soldiers in the field have different jobs, subsets of a type of immune cell that polices the barriers of the body can promote unique and opposite immune responses against the same ...

From HIV to cancer, IL-37 regulates immune system

November 3, 2014
A University of Colorado Cancer Center study published in this month's Proceedings of the National Academy of Sciences describes the activity of a recently discovered communication molecule of the body's immune system, Interleukin ...

New cancer vaccine one step closer

June 2, 2016
A team led by Monash University and the University of Queensland has developed a new approach to harnessing the body's immune system to fight disease that could pave the way for a new class of cancer vaccine.

Recommended for you

Obesity and health problems: New research on a safeguard mechanism

March 16, 2018
Obesity and its negative impacts on health - including metabolic syndrome, type-2 diabetes mellitus and cardiovascular complications - are a global pandemic (Taubes, 2009). The worldwide incidence of obesity has more than ...

Immune system 'double agent' could be new ally in cancer fight

March 16, 2018
St. Jude Children's Research Hospital scientists have discovered that an enzyme called TAK1 functions like a "double agent" in the innate immune response, serving as an unexpected regulator of inflammation and cell death. ...

Artificial sweetener Splenda could intensify symptoms in those with Crohn's disease

March 15, 2018
In a study that has implications for humans with inflammatory diseases, researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener ...

Researchers identify common biological features of different types of asthma

March 14, 2018
A team of researchers from the NIHR Leicester Biomedical Research Centre - a partnership between Leicester's Hospitals, the University of Leicester and Loughborough University - has identified biological variations in lung ...

Scientists discover treatment target for sepsis

March 14, 2018
In a study published in Nature Communications, Northwestern Medicine scientists demonstrated the key role a molecule called oxPAPC plays in regulating the inflammatory response—findings which could inform the development ...

Researcher creates 'Instagram' of immune system, blending science, technology

March 10, 2018
Being on the cutting edge of science and technology excites Hollings Cancer Center (HCC) researcher Carsten Krieg, Ph.D. Each day, he walks into his lab that houses a mass cytometry machine aptly labeled Helios. Krieg explains ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Dec 02, 2017
Would this be related to the effectiveness of BCG challenge 'scratch test', sometimes delivered via a scary, but superficial nip by a multi-clawed pincher ??

{ I remember the big 'toughs' of our school's rugby football team fainting in droves at the sight of that Dreadful Device. Me ? Nah, it's like playing tag with a sassy kitten... }

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.