Induction of Strain-Transcending Immunity againstPlasmodium chabaudi adamiMalaria with a Multiepitope DNA Vaccine

Abstract

A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9؉ pool, 303 plasmids) and >50 aa (V50؉ pool, 56 plasmids), respectively. The V9؉ and V50؉ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50؉ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami.

Macrophage Migration Inhibitory Factor: A Downregulator of Early T Cell-Dependent IFN-γ Responses in Plasmodium chabaudi adami (556 KA)-Infected Mice

“…Apart from ADCI, opsonising antibodies enhance the phagocytosis and elimination of infected red blood cells by macrophages in vitro and are induced by vaccines protecting BALB/c mice against P.c. adami infection (46, 47). The potential regulatory role for MIF on IL-4 responses in granulocytes, on Th2 sketching and on protection in malaria is interesting as these cells, centrally involved in the acute inflammatory reactions to allergens, are now being considered general inducers of Th2 responses (34).…”

RETRACTED ARTICLE: Recent developments in DNA vaccination approaches against poultry coccidiosis and its future endeavours

“…There is a possibility that the same principle can be applied to DNA vaccines by producing epitope vaccines against Eimeria infections. Scorza et al (2005) described a multi-epitope malaria vaccine and showed that the vaccine conferred protection against a heterologous parasite infection in BALB/c mice studies (Scorza et al, 2005). Similarly, Tian et al (2008) showed that a multi-epitope DNA vaccination led to a dramatic augmentation of humoral and cellular responses, and provided up to an 80% immune protection against infectious bronchitis virus (IBV) (Tian et al, 2008).…”

Potent Antimalarial and Transmission‐Blocking Activities of Centanamycin, a Novel DNA‐Binding Agent

“…Procedures for Plasmodium chabaudi adami animal experiments were approved by the Macdonald Campus Animal Care Committee of McGill University, and procedures for Plasmodium berghei animal experiments were approved by the New York University School of Medicine Institutional Animal Care and Use Committee. Groups of female BALB/c mice (18 -20 g) were injected intraperitoneally (ip) on day 0 with rodent malarial parasites from an infected donor mouse [14]. Mice were infected with 0.5 ϫ 10 5 -1 ϫ 10 5 parasites.…”

“…Parasitemia was monitored from thin blood films, as described elsewhere [9]. The total parasite burden per mouse was calculated from the cumulative parasitemia throughout the trial [14,15]. A 4-day suppression test was used, as described elsewhere [16].…”