Dendritic cell vaccines allow rapid response

The efficiency of vaccinations could be dramatically improved by
combining peptide antigens with dendritic cells, according to new
research published in the journal Nature Medicine (July issue).

The approach, in which dendritic cells are engineered to carry peptide antigens on their surfaces, could allow people to gain protection from diseases in just one short and do away with the need for booster injections - given over an extended period - to provide effective immunity.

Truncating the period before effective immunity is in place could have significant consequences for vaccines aimed at agents used in bioterrorism, where the window for vaccination could be small, and for immunotherapy of diseases such as cancer where an early immune response is crucial.

Long-lasting immunity typically relies on the efficient boosting of memory T-cell numbers to protective levels.

Badovinac et al​ show in their study that mice vaccinated with dendritic cells coated with peptides from the bacterium Listeria monocytogenes​ could mobilise an effective, long-lasting immune response faster than mice who were given a vaccine based on killed bacteria.

Dendritic cells patrol the body for pathogens such as bacteria or viruses. Contact with the invading microbe 'arms' the dendritic cells, which then travel from the infection site to the lymph nodes where they activate T cells. These stimulated T cells proliferate and are transformed, first into effector cells that fight the infection and then into memory cells, which respond quickly if the same pathogen is encountered a second time. These are the basis of long-term immunity against infection.

But this T cell transformation process takes time, and memory T cells generally only proliferate in response to a second infection - or a a booster vaccination.

Specifically, the researchers found that a specific population of T cells - called CD8+ memory cells - expanded in response to the dendritic vaccine challenge much faster than in mice given the attenuated vaccine.

"Vaccination with peptide-coated dendritic cells (DCs) generated CD8+ T cells with the phenotype and function of memory cells within 4-6 days,"​ write the scientists. This compares to several weeks for normal vaccination

The DC-vaccinated mice were more resistant to bacterial infection bacteria, consistent with an increased level of protective immunity.

"These early memory CD8+ T cells underwent vigorous secondary expansion in response to a variety of booster immunizations, leading to elevated numbers of effector and memory T cells and enhanced protective immunity,"​ they added.

Related topics Clinical trials & development

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