Reduced immunogenicity of DNA vaccine plasmids in mixtures

Abstract

We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-g responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-g responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-g responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.

Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF

“…We have also shown in another study this reduction in immune responses to individual proteins when given as a nine-gene mixture to mice. 23 In that study, we demonstrated that the reduction was due to interference among plasmids in a mixture as opposed to a dose effect of the plasmids. 23 Thus, we believe that the reduction in immune responses to individual proteins in the mixture, as opposed to when they were delivered alone in the current studies, was due to interference.…”

Comparative Testing of Six Antigen-Based Malaria Vaccine Candidates Directed Toward Merozoite-StagePlasmodium falciparum

“…Thus, the mixture of the two individual vaccine candidate components may have resulted in some kind of immunological interference that led to some suppression of the anti-MSP-1 19 IgG response in these animals. This may be due to antigenic competition, a phenomenon known to immunology for over 100 years, and noted in recent immunizations with multiple recombinant malaria antigen plasmids (22). In some cases, a dominant antigen can prevent or reduce the antibody response to another antigen, if the two are administered simultaneously and in the same formulation.…”

DNA prime–protein boost strategies protect cattle from bovine viral diarrhea virus type 2 challenge

“…In other instances interference between plasmids has been demonstrated. A nine-plasmid DNA vaccine encoding malaria antigens from the sporozoite, exoerythrocytic and erythrocytic stages of the parasite elicited dramatically reduced immune responses to the component antigens compared with the responses to the plasmids given singly (Sedegah et al, 2004). Furthermore, a plasmid encoding bovine herpesvirus-1 glycoprotein D interfered with plasmids encoding parainfluenzavirus-3 HN or influenza HA, when co-delivered in a mixture, whereas the HN-and HAencoding plasmids did not cause interference (Braun et al, 1998).…”