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-γ 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.

Mucosally DeliveredSalmonellaLive Vector Vaccines Elicit Potent Immune Responses against a Foreign Antigen in Neonatal Mice Born to Naive and Immune Mothers

“…Our results are in line with previous reports showing that vaccine-induced T-cell responses appear to remain intact despite the presence of maternal antibodies (12,40). This can be attributed to the incapacity of maternal antibodies to interfere with vaccine antigens that, following cell invasion, become available for presentation via major histocompatibility complex molecules (40).…”

Plasmodium falciparum-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique

“…There are concerns about the adverse effect of maternal immunity and the immaturity of infants' immune systems on the induction of adequate antibody and effector T-cell IFN-␥ responses (Th1) by malaria vaccines in neonates and infants living in areas of endemicity (35,36). In this safety/efficacy trial in infants, RTS,S/AS02D immunization induced high titers of anti-CSP antibodies, suggesting that the presence of maternally transferred antibodies at a young immunization age did not significantly modify the antibody immune response (4).…”

DNA Vaccines: Progress and Challenges

“…Malaria is acquired at a young age, and for complete protection, it likewise may be necessary to immunize at a very early age. It was shown experimentally that 7-day-old mice with maternal Abs could acquire CD8 ϩ related protective immunity with a circumsporozoite protein DNA vaccine together with GM-CSF, followed by boosting with the same Ag in a poxvirus vector at 1 mo of age (63). In contrast, a malaria DNA vaccine prime with a modified vaccinia Ankara boost encoding sporozoite and liver stage epitopes was weakly immunogenic in healthy, malaria-naive, U.K. adults, and was insufficient to protect against malaria challenge by infected mosquitoes (64).…”