Immunological responses of neonates and infants to DNA vaccines

Area of Science:

• Immunology
• Vaccinology
• Parasitology

Background:

• Infant malaria deaths are a significant concern in sub-Saharan Africa.
• Malaria vaccines require administration to infants, who may have maternally acquired antibodies.
• Neonatal CD8(+) T-cell responses, critical for pre-erythrocytic malaria vaccines, are often suboptimal.

Purpose of the Study:

• To assess the efficacy of a Plasmodium yoelii circumsporozoite protein (PyCSP) DNA vaccine in neonatal mice.
• To determine if neonatal immunization with a PyCSP DNA vaccine, followed by a boost, confers protection against malaria.
• To evaluate the role of CD8(+) T cells in vaccine-induced protection in neonates.

Main Methods:

• BALB/c mice were immunized neonatally (7 days) with a PyCSP DNA vaccine and granulocyte-macrophage colony-stimulating factor (DG).
• Neonates were boosted at 28 days with a PyCSP expressing pox virus.
• Immune responses, including CD8(+) T cells, interferon-gamma, and cytotoxic T-lymphocyte activity, were measured.
• Protection rates were compared between neonatally and adult-immunized mice.

Main Results:

• Neonatal immunization followed by adult boosting achieved 93% protection, comparable to adult immunization (70%).
• Protection was dependent on CD8(+) T cells and associated with robust anti-PyCSP interferon-gamma and cytotoxic T-lymphocyte responses.
• Mice born of immune mothers also showed protection and strong T-cell responses after vaccination.

Conclusions:

• A vaccination strategy involving neonatal priming and adult boosting is effective against malaria.
• This approach can induce protective CD8(+) T-cell immunity in neonates, overcoming typical immune limitations.
• The findings support the evaluation of this immunization strategy for infants in high-malaria-burden regions.