Immunological responses of neonates and infants to DNA vaccines.
In some parts of sub-Saharan Africa, it is believed that most of the deaths attributed to malaria occur in infants. For this and other logistical reasons, if a malaria vaccine is developed and licensed, it will have to be administered to neonates or young infants, when they have maternally acquired antibodies against malaria parasite proteins. Pre-erythrocytic malaria vaccines in development rely on CD8(+) T cells as immune effectors, yet some studies indicate that neonates do not mount optimal CD8+ T-cell responses. We report that BALB/c mice first immunized as neonates (7 d) with a Plasmodium yoelii circumsporozoite protein (PyCSP) DNA vaccine mixed with a plasmid expressing murine granulocyte macrophage-colony stimulating factor (DG) and boosted at 28 d with pox virus expressing PyCSP were protected (93%) as well as mice immunized entirely as adults (70%). Like adults, protection was dependent on CD8(+) T cells and accompanied by excellent anti-PyCSP interferon-gamma and cytotoxic T-lymphocyte responses. Mice born of immune mothers (previously exposed to P. yoelii parasites or immunized with the same vaccine given to the neonates) were also protected and had excellent T-cell responses. These data support assessment of this immunization strategy in neonates/young infants in areas where malaria exacts the greatest toll.
Sedegah
Martha
M
Malaria Program, Naval Medical Research Center, Silver Spring, MD, USA.
Hoffman
Stephen L
SL
D017954:Africa South of the Sahara; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008288:Malaria / Q000276:immunology* / Q000401:mortality; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology*; D011212:Poxviridae / Q000235:genetics / Q000276:immunology; D011247:Pregnancy; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C041595:circumsporozoite protein, Protozoan