Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly

Abstract

The number of memory CD8 T cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. Therefore, rapid induction of protective numbers of effector and memory CD8 T cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. Many studies have shown that amplifying T-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. In contrast, immunization with peptide-coated mature dendritic cells (DCs) results in a CD8 T-cell response exhibiting accelerated acquisition of memory characteristics, including the ability to respond to booster immunization within days of initial priming. However, personalized DC immunization is too costly, labor intensive, and time-consuming for large-scale vaccination. Here, we demonstrate that in vivo cross-priming with cell-associated antigens or antigen-coated, biodegradable microspheres in the absence of adjuvant quickly generates CD8 T cells that display the phenotype and function of long-term memory populations. Importantly, cross-primed CD8 T cells can respond to booster immunization within days of the initial immunization to generate rapidly large numbers of effector and memory T cells that can protect against bacterial, viral, and parasitic infections, including lethal influenza and malaria-causing Plasmodium infection. Thus, accelerated CD8 T-cell memory after in vivo cross-priming in the absence of adjuvant is generalizable and can be exploited to generate protective immunity rapidly.

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect

“…This is an important property that has not been seen with a lot of other vaccines. With these vaccines, after priming, the immune system remains insensitive to further vaccinations and only after the T cell contraction phase immune responses can be boosted [14]. On the other hand, the active tumor immunotherapy for these vaccines spans several months when multiple vaccinations are administered.…”

IL-15 regulates memory CD8+ T cell O-glycan synthesis and affects trafficking

“…Although many of these newly formed daughter cells are short-lived, a substantial percentage will survive the contraction phase and persist for long periods of time as memory cells, capable of providing protection from pathogen reinfection (3)(4)(5). In fact, memory CD8 + T cell populations are able to confer host protection against infection in a number of different experimental models (6)(7)(8)(9).…”

Vaccine Technologies Against Avian Influenza: Current Approaches and New Directions

“…210 In addition, antigen-coated PLGA microspheres have been shown to cross-prime CD8 + T cells in vivo resulting in long term memory populations. 211 Likewise, PLGA particles encapsulating an influenza DNA vaccine demonstrated successful transfection of cells with increased antibody titers over a period of 8 weeks. 212 Other benefits of encapsulation into poly(esters) include antigen protection from proteolytic cleavage, enhanced delivery to APCs, internalization, endosomal escape, and cross presentation.…”