title: Successful induction of CD8 T cell-dependent protection against malaria by sequential immunization with DNA and recombinant poxvirus of neonatal mice born to immune mothers.
abstract: In some parts of Africa, 50% of deaths attributed to malaria occur in infants less than 8 mo. Thus, immunization against malaria may have to begin in the neonatal period, when neonates have maternally acquired Abs against malaria parasite proteins. Many malaria vaccines in development rely upon CD8 cells as immune effectors. Some studies indicate that neonates do not mount optimal CD8 cell responses. We report that BALB/c mice first immunized as neonates (7 days) with a Plasmodium yoelii circumsporozoite protein (PyCSP) DNA vaccine mixed with a plasmid expressing murine GM-CSF (DG) and boosted at 28 days with poxvirus expressing PyCSP were protected (93%) as well as mice immunized entirely as adults (70%). Protection was dependent on CD8 cells, and mice had excellent anti-PyCSP IFN-gamma and cytotoxic T lymphocyte responses. Mice born of mothers previously exposed to P. yoelii parasites or immunized with the vaccine were protected and had excellent T cell responses. These data support assessment of this immunization strategy in neonates/young infants in areas in which malaria exacts its greatest toll.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.forename: Maria
authors.initials: M
authors.lastname: Belmonte
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Walter R
authors.initials: WR
authors.lastname: Weiss
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Jones
authors.forename: Minh
authors.initials: M
authors.lastname: Lu
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carucci
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000096:biosynthesis / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D007112:Immunity, Maternally-Acquired / Q000235:genetics; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D007273:Injections, Intramuscular; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011212:Poxviridae / Q000235:genetics / Q000276:immunology*; D011247:Pregnancy; D034101:Sporozoites / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D019444:Vaccines, DNA