Immune responses induced by intramuscular or gene gun injection of protective deoxyribonucleic acid vaccines that express the circumsporozoite protein from Plasmodium berghei malaria parasites.

Abstract

The circumsporozoite protein (CSP) is a target for effector Ab and cell mediated immunity against malaria parasites; DNA vaccination can induce both types of effector response. The immunogenicity and efficacy of two DNA plasmids expressing different amounts of Plasmodium berghei CSP were evaluated by immunizing BALB/c mice i.m. or epidermally and by varying the number of immunizations (one to three doses) and the interval between immunizations. Expanding the interval gave the strongest effect, increasing efficacy and antibody boosting, and, in the case of epidermal vaccination, promoting a switch in CSP-specific IgG isotypes from IgG1 to a balance with IgG2a. The strongest humoral immune response and the greatest level of protection were induced by vaccinating epidermally with high expresser plasmid, using a gene gun to administer three doses at 6-wk intervals. For this group, the mean, repeat-specific, prechallenge antibody titer among mice not infected after challenge was significantly higher than that in infected mice, but the mean prechallenge titers for antibody reactive with whole sporozoites were not significantly different. The interval-dependent induction of IgG2a antibodies by epidermal vaccination contradicts the widely held belief that antibody responses induced by this method are restricted to those that are Th2 dependent.

Comparison of Humoral Immune Responses Elicited by DNA and Protein Vaccines Based on Merozoite Surface Protein-1 fromPlasmodium yoelii, a Rodent Malaria Parasite

“…Injection with DNA vaccines leads to lower but longer in vivo expression of the encoded Ags, and, since DNA vaccination takes longer to induce Ab immune responses, it may take longer for avidity increases to become apparent. In support of this possibility, Lyon and his colleague recently reported that increasing the interval between DNA immunization of mice increased the levels of Abs produced (57). To address the issue of longer intervals between DNA injections, we have done an experiment with the V3 DNA vaccine, immunizing three times at weeks 0, 12, and 32.…”

Humoral and Cellular Immune Responses Induced by Bivalent DNA Vaccines Expressing Fusion Capsid Proteins of Porcine Circovirus Genotypes 2a and 2b

“…Enhancement of CD4 (helper) T cell response may in turn enhance B and CD8 T cell responses as CD4 T (T helper) cells are involved in the stimulation of both B and CD8 T cells [ 25 ]. Previous studies showed that the inclusion of a secretory signal sequence in the immunogen enhanced the induction of immune responses when compared to the non-secretory forms [ 26 , 27 ]. Thus, it is useful to address whether a PCV2 capsid-based immunogen would be more immunogenic in a secreted form.…”