DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations.

Abstract

Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been tested for their ability to raise protective immunity against lethal influenza challenges of the same subtype. In trials using two inoculations of from 50 to 300 pg of purified DNA in saline, 67-95% of test mice and inoculations were undertaken (i) by a route that supports unusually efficient transfection (muscle), (ii) by routes that support less efficient transfection but represent routes frequently used for the administration of an antigen to a test animal (subcutaneous, intraperitoneal), and (iii) by routes that support less efficient transfection but deliver DNA to tissues with high levels of local immune surveillance (skin and respiratory passages).The effect of the route of inoculation on DNA vaccination was evaluated in murine and avian influenza virus models. In both models, the vaccine consisted of purified plasmid DNA that had been designed to express an influenza virus hemagglutinin glycoprotein. This glycoprotein mediates adsorption and penetration of virus and represents a major target for neutralizing antibody (16, 17). A number of antigenically distinct subtypes of hemagglutinin glycoproteins are found in naturally occurring influenza virus infections (18). In the murine model, plasmid DNA expressing the hemagglutinin subtype 1 (Hi) protein was used to protect against a lethal challenge with a mouse-adapted influenza virus with an identical Hi gene. In the chicken model, DNA expressing the hemagglutinin subtype 7 (H7) protein was used to vaccinate against a lethal H7 virus with an antigenically distinct H7 glycoprotein (19 §To whom reprint requests should be addressed.11478

Heterologous HA DNA vaccine prime—inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses

“…In many previous studies, mouse models were frequently used with the potential benefit to observe the protective effect of vaccines when immunized mice are subject to a lethal influenza virus challenge. On the other hand, achieving protection in mouse models is relatively easy even when the levels of protective antibodies were below detection prior to challenge [22]. At the same time, each mouse can only provide a limited amount of blood which does not allow for the extensive array of antibody assays used to characterize different antibody responses.…”

Superiority of the ear pinna over muscle tissue as site for DNA vaccination

“…over a s.c. tumor inoculation site for induction of a Th1 type cytokine response. 26 Fynan et al 35 observed that i.m. applications were weaker in elicting immune responses than gene gun treatment.…”

Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF

“…[1][2][3][4] Instead of using an entire antigen, one alternative approach is to use an epitope from that antigen. 5 MUC-1, which is expressed on the surface of many malignant cells, contains multiple tandem repeats of the PDTRP epitope.…”