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Abstract: To differentiate prenatal effects of plasmid growth hormone-releasing hormone (GHRH) treatment from maternal effects mediated by lactation on long-term growth of offspring, a cross-fostering study was designed. Pregnant sows (n =12) were untreated (n =6) or received either a Wt-GHRH (n =2) or HV-GHRH (n =4) plasmid. At birth, half of each litter was cross-fostered (treated to controls and controls to treated only). Piglets from plasmid-injected sows were heavier at birth (HV-GHRH, 1.65±0.07kg; Wt-GHRH, 1.46±0.05kg vs. Controls, 1.27±0.03kg; P ≥0.001) and at weaning (Wt-GHRH, 6.01±0.21kg and HV-GHRH, 6.34±0.15kg vs. Controls, 5.37±0.14kg; P ≥0.02, respectively). Control piglets cross-fostered to plasmid-injected sows grew faster to weaning (Wt-GHRH, 5.61±0.15kg and HV-GHRH, 5.70±0.29kg vs. Controls, 5.08±0.22kg; P >0.05, respectively). Piglets from plasmid-injected sows that suckled on control sows were larger than control piglets on control sows (Wt-GHRH, 5.93±0.20kg and HV-GHRH, 6.2±0.19kg vs. Controls, 5.08±0.22kg; P >0.05, respectively), but smaller than their littermates left on their treated mothers. The observed improvements were maintained until the end of the study when the offspring were 170-day-old. The results suggest that the improved growth of offspring of GHRH plasmid-treated sows pre-weaning is attributable to improved maternal performance, while after weaning the effects on the pituitary component are relevant. [Copyright &y& Elsevier]

Abstract: Naïve Indian rhesus macaques were immunized with a mixture of optimized plasmid DNAs expressing several SIV antigens using in vivo electroporation via the intramuscular route. The animals were monitored for the development of SIV-specific systemic (blood) and mucosal (bronchoalveolar lavage) cellular and humoral immune responses. The immune responses were of great magnitude, broad (Gag, Pol, Nef, Tat and Vif), long-lasting (up to 90 weeks post third vaccination) and were boosted with each subsequent immunization, even after an extended 90-week rest period. The SIV-specific cellular immune responses were consistently more abundant in bronchoalveolar lavage (BAL) than in blood, and were characterized as predominantly effector memory CD4+ and CD8+ T cells in BAL and as both central and effector memory T cells in blood. SIV-specific T cells containing Granzyme B were readily detected in both blood and BAL, suggesting the presence of effector cells with cytolytic potential. DNA vaccination also elicited long-lasting systemic and mucosal humoral immune responses, including the induction of Gag-specific IgA. The combination of optimized DNA vectors and improved intramuscular delivery by in vivo electroporation has the potential to elicit both cellular and humoral responses and dissemination to the periphery, and thus to improve DNA immunization efficacy. [Copyright &y& Elsevier]