Electroporation Enables Plasmid Vaccines to Elicit CD8+ T Cell Responses in the Absence of CD4+ T Cells

Abstract

In vivo electroporation dramatically enhances plasmid vaccine efficacy. This enhancement can be attributed to increased plasmid delivery and, possibly, to some undefined adjuvant properties. Previous reports have demonstrated CD8+ T cell priming by plasmid vaccines is strongly dependent upon CD4+ T cell help. Indeed, the efficacy of a plasmid vaccine expressing Escherichia coli β-galactosidase was severely attenuated in MHC class II-deficient (C2D) mice. To determine whether electroporation could compensate for the absence of CD4+ T cell help, C2D mice were immunized by a single administration of plasmid in combination with electroporation using two conditions which differed only by the duration of the pulse (20 or 50 msec). Both conditions elicited robust cellular and humoral responses in wild-type mice, as measured by IFN-γ ELISPOT, anti-β-galactosidase ELISA, and protection from virus challenge. In C2D mice, the cellular response produced by the vaccine combined with the 50-msec pulse, as measured by ELISPOT, was identical to the response in wild-type mice. The 20-msec pulse elicited a milder response that was approximately one-fifth that of the response elicited by the 50-msec pulse. By contrast, the 20-msec conditions provided comparable protection in both wild-type and C2D recipients whereas the protection elicited by the 50-msec conditions in C2D mice was weaker than in wild-type mice. Further investigation is required to understand the discordance between the ELISPOT results and outcome of virus challenge in the C2D mice. Nonetheless, using this technique to prime CD8+ T cells using plasmid vaccines may prove extremely useful when immunizing hosts with limiting CD4+ T cell function, such as AIDS patients.

The CD8+ T Cell Population Elicited by Recombinant Adenovirus Displays a Novel Partially Exhausted Phenotype Associated with Prolonged Antigen Presentation That Nonetheless Provides Long-Term Immunity

“…injection of 10 7 PFU Vacc-ESOVA (a gift from J. Yewdell, National Institute of Allergy and Infectious Diseases, Bethesda, MD), which expresses an endoplasmic reticulum-targeted SIINFEKL epitope. Seven days later, virus replication was measured in the ovaries as described previously (33).…”

Ear Pinna: A Privileged DNA Electroporation Site for Inducing Strong Th1 Immune Responses

“…Also, however, the induction of an inflammatory response, due to the physical stimulation of skin cells by EP, might be crucial for enhancing immune responses [80]. This undefined adjuvant effect might be possibly mediated through local minor tissue damage and release of inflammatory factors [79,81,82]. Recent data suggest that in addition to enhancing gene delivery, EP provides adjuvant-like effects [82,83].…”

“…This undefined adjuvant effect might be possibly mediated through local minor tissue damage and release of inflammatory factors [79,81,82]. Recent data suggest that in addition to enhancing gene delivery, EP provides adjuvant-like effects [82,83]. Several reports have shown that the local effect by EP is responsible for the generation of an inflammatory environment with immune cell infiltration.…”

Transdermal Drug Delivery and Methods to Enhance It

“…Способ электропорации сделал возможным чрескожную доставку лекарств при воспалительных заболевани-ях [49]; обезболивании [50], химиотерапии опухо-лей [51][52][53][54][55][56][57]. Кроме того, электропорация расширяет возможности генной терапии, позволяющий введе-ние ДНК, генов в клетки [58,59], а также для вак-цин [60][61][62].…”