RESUMO
In these studies, we address the ability of DNA encoding Th1 cytokines to bias the isotype of antibody raised by neonatal or adult immunization with an influenza hemagglutinin expressing DNA (HA-DNA). Neonatal mice coimmunized with HA-DNA and either IL-12 or IFN-gamma-expressing DNA developed IgG2a-biased immune responses, regardless of inoculation method. In contrast, the Th1 genetic adjuvants had no effect on IgG subtype patterns in adults. In neonatal mice, the Th1 genetic adjuvants also shifted the pattern of lymphokine production by recall splenocytes from a mixed response of IFN-gamma and IL-5 to exclusively IFN-gamma. In adults, despite the failure to change the isotype pattern of the antibody response, a shift towards IFN-gamma production also occurred for recall splenocytes following coimmunzation with IL-12. Thus, coinoculation of Th1 genetic adjuvants had greater effects on the nature of the immune response in the neonate than in adults.
Assuntos
Animais Recém-Nascidos/imunologia , Isotipos de Imunoglobulinas/biossíntese , Interferon gama/imunologia , Interleucina-12/imunologia , Células Th1/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/genética , Envelhecimento/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Isotipos de Imunoglobulinas/imunologia , Interferon gama/análise , Interferon gama/genética , Interleucina-12/genética , Interleucina-5/análise , Interleucina-5/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Vacinação , Vacinas de DNA/genéticaRESUMO
Maternal antibody is the major form of protection from disease in early life when the neonatal immune system is still immature; however, the presence of maternal antibody also interferes with active immunization, placing infants at risk for severe bacterial and viral infection. We tested the ability of intramuscular and gene gun immunization with DNA expressing influenza virus hemagglutinin (HA) and nucleoprotein (NP) to raise protective humoral and cellular responses in the presence or absence of maternal antibody. Neonatal mice born to influenza virus-immune mothers raised full antibody responses to NP but failed to generate antibody responses to HA. In contrast, the presence of maternal antibody did not affect the generation of long-lived CD8(+) T-cell responses to both HA and NP. Thus, maternal antibody did not affect cell-mediated responses but did affect humoral responses, with the ability to limit the antibody response correlating with whether the DNA-expressed immunogen was localized in the plasma membrane or within the cell.
