DNA immunization of infants: potential and limitations

Butts, Cherie; Zubkoff, Ira; Robbins, Deanna S.; Cao, Shui; Sarzotti, Marcella

doi:10.1016/s0264-410x(98)00106-6

Cited by 25 publications

(10 citation statements)

References 28 publications

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“…Since memory T cells have a greater and faster ability to respond to low doses of Ag than their naive counterparts (25), we measured responses to a rechallenge with a low viral dose (5 PFU, boosting dose) (26). Unless otherwise specified, the experiments described hereafter used a boosting dose as a rechallenge.…”

Section: Secondary Cytotoxic Responses To Casmentioning

confidence: 99%

“…Limited viral replication may control the amount of virus presented to T cells in the neonate, much like decreasing the initial priming dose of Cas. Neonatal DNA immunization, which produces low sustained Ag synthesis, has been another successful strategy that leads to long-lasting CD8 ϩ T cell responses (15,16,26). This further emphasizes the need for determining ways to optimize neonatal priming, which will largely influence the stability of a secondary response.…”

Section: Figure 4 Cd8mentioning

confidence: 99%

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Enhanced Type 1 Immunity After Secondary Viral Challenge in Mice Primed as Neonates

Fadel

Ozaki

Sarzotti

2002

The Journal of Immunology

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The goal of infant immunization against viral infection is to develop protective long term memory responses. Priming neonatal mice with a low dose of Cas-Br-E murine leukemia virus (Cas) results in adult-like, type 1 protective responses. However, other studies suggest that Ag priming of neonates leads to an increase in type 2 secondary responses even when primary responses were type 1. We assessed whether type 1 CD8+ T cell-mediated responses developed in murine neonates are maintained after secondary challenge with Cas in adulthood. Despite the induction of significant anti-viral CD8+-mediated cytotoxic T lymphocyte and IFN-γ responses, initial neonatal priming led to a lower frequency of virus-specific T cells compared with adult priming. Adult frequencies were reached in mice primed as neonates only after secondary challenge in adulthood. A nonspecific and transient CD4+-mediated IL-4 response was present in all groups after secondary challenge with Cas or medium, indicating that this rise in type 2 cytokine production was not unique to mice that had been primed as neonates. Rather, type 1 anti-viral memory CD8+ T cell responses developed in neonatal mice are stable, protective, and enhanced after secondary challenge.

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Section: Secondary Cytotoxic Responses To Casmentioning

confidence: 99%

Section: Figure 4 Cd8mentioning

confidence: 99%

Enhanced Type 1 Immunity After Secondary Viral Challenge in Mice Primed as Neonates

Fadel

Ozaki

Sarzotti

2002

The Journal of Immunology

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“…Vaccination has provided a very cost-effective approach to prevent infectious disease, but the induction of tolerance or a state of nonresponsiveness was previously thought to preclude vaccination as an effective therapy in the fetus or newborn (3). Increasing evidence, however, indicates that fetal immunization can induce active immunity in the newborn.…”

mentioning

confidence: 99%

Oral DNA Vaccination In Utero Induces Mucosal Immunity and Immune Memory in the Neonate

Gerdts

Snider

Brownlie

et al. 2002

The Journal of Immunology

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Infectious diseases are responsible for a significant number of deaths during the first weeks of life. Some of the salient pathogens include HSV, HIV, hepatitis B virus, group B streptococcus, Haemophilus sp., and Chlamydia sp. The vertical transmission of many of these pathogens significantly increases the risk of neonatal infection. We recently reported that oral DNA immunization in utero induced high serum Ab titers and cell-mediated immunity in fetal lambs. In this study, we demonstrate immune memory and mucosal immunity in newborn lambs following oral DNA immunization of the fetus. A single oral exposure in utero to plasmid DNA encoding a truncated form of glycoprotein D of bovine herpesvirus-1 induced detectable immune responses in 80% (12 of 15) of newborn lambs. There was no evidence for the induction of immune tolerance in nonresponding lambs. Responding lambs displayed both systemic and mucosal immune responses and reduced virus shedding following intranasal challenge. Furthermore, strong anamnestic responses were evident for at least 3 mo after birth. The efficacy of in utero oral DNA immunization was further demonstrated with the hepatitis B surface Ag, and protective serum Ab titers occurred in 75% of immunized lambs. Thus, the present investigation confirms that oral DNA immunization in utero can induce both mucosal and systemic immune responses in the neonate and that this immunity has the potential to prevent vertical disease transmission.

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“…Such vaccination strategies as this may have implication for the avoidance of vertical transmission of disease. In particular, the induction of active immunity (as opposed to tolerance) in the newborn may be of interest as the induction of tolerance was previously thought to preclude effective vaccination in the foetus or newborn (Butts et al, 1998). The value of this is strengthened by the observation that no evidence for tolerance was seen in non-responding animals following oral immunisation of foetal lambs (Gerdts et al, 2002).…”

Section: The Potential For Oral Delivery Of Plasmid Dnamentioning

confidence: 99%

Oral Plasmid DNA Delivery Systems for Genetic Immunisation

Somavarapu

Bramwell

Alpar

2003

Journal of Drug Targeting

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The use and optimisation of plasmid DNA delivery systems for the purposes of eliciting transgene specific immune responses to orally administered DNA encoded antigen represents a significant challenge. Here, we have outlined a multicomponent polymer modified liposomal delivery system that offers potential for oral administration of plasmid DNA. It is shown that the polymer/liposome formulated DNA is able to elicit markedly enhanced transgene specific cytokine production following in vitro restimulation of splenocytes with recombinant antigen. This is discussed with reference to recent publications and the potential of plasmid DNA delivery systems for the purposes of genetic immunisation, as reported in selected literature, is assessed.

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DNA immunization of infants: potential and limitations

Cited by 25 publications

References 28 publications

Enhanced Type 1 Immunity After Secondary Viral Challenge in Mice Primed as Neonates

Enhanced Type 1 Immunity After Secondary Viral Challenge in Mice Primed as Neonates

Oral DNA Vaccination In Utero Induces Mucosal Immunity and Immune Memory in the Neonate

Oral Plasmid DNA Delivery Systems for Genetic Immunisation

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