Induction of antigen-specific CD8+ T cells, T helper cells, and protective levels of antibody in humans by particle-mediated administration of a hepatitis B virus DNA vaccine

Preclinical and clinical progress of particle-mediated DNA vaccines for infectious diseases

“…These studies showed that a minimum of 1.0 g and 2 delivery sites was required to induce a detectable response in most subjects but higher responses and a better responder rate could be achieved by increasing the dose to 4.0 g DNA administered into 4 delivery sites [69,70]. A subsequent HBsAg DNA vaccine study in pre-immune subjects showed that increasing the DNA dose up to 8.0 g (4 delivery sites) provided no additional beneWt, indicating that a 4.0 g DNA dose was suYcient for PMED in humans.…”

“…A PMED hepatitis B DNA vaccine trial was the Wrst to demonstrate that DNA immunization could be used to eVectively induce humoral responses in humans [69]. Immunization with 3 doses of 1-4 g of DNA induced robust antibody in 100% of the immunized subjects at levels that exceeded the minimum required for protective immunity (10 mIU/ml).…”

Preclinical and Clinical Safety Studies on DNA Vaccines

“…[68][69][70][71] No changes occurred in vital signs, complete blood counts, serum creatinine, other blood chemical parameters, or urinalysis. 68,72,73 No significant increase in antinuclear antibodies and anti-DNA antibodies were detected. 68,[72][73][74] Serum liver chemical values increased in some subjects, but returned to normal during the study.…”

“…68,72,73 No significant increase in antinuclear antibodies and anti-DNA antibodies were detected. 68,[72][73][74] Serum liver chemical values increased in some subjects, but returned to normal during the study. 68 Even at doses as high as 2500 µg per injection no serious adverse effects, no antinuclear or anti-DNA antibodies, and no abnormalities in blood chemistry or urinalysis were observed.…”

“…74 In a second trial, designed as a dose escalation study with administration of DNA concentrations from 1 µg to 4 µg in total, the vaccine elicited both humoral and cellular immune responses. 73 In a trial with human subjects that did not respond to conventional hepatitis B vaccines the DNA vaccine elicited antibody responses in 12 out of 16 subjects. 71 DNA vaccination strategies against HIV focus on the induction of HIV-specific CTL responses in order to eliminate infected cells.…”