BackgroundWe have previously described a four antigen malaria vaccine consisting of DNA plasmids boosted by recombinant poxviruses which protects a high percentage of rhesus monkeys against Plasmodium knowlesi (Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine.MethodologyIn three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given iv 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-γ, and by ELISA.Conclusions1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher interferon-γ ELIspot responses to the PkCSP antigen correlated with earlier appearance of parasites in the blood, despite the fact that PkCSP vaccines had a protective effect.
Background and purpose:The purpose of this study is to determine the impact of melanin on skin response to single 3.8 micron, eight microsecond laser pulses and the difference in lesion formation thresholds for input into laser safety standards. Williams et al., performed a study examining laser tissue interaction from 3.8-micron lasers in lightly pigmented Yorkshire pigs (Sus scrofa domestica). 1 However, studies performed by Eggleston et al comparing pigmented and lightly pigmented skin with human skin found that the Yucatan mini-pig is a superior model for laser skin exposures. 2 Methods: Five Yucatan mini-pigs under general anesthesia were exposed to 3.8 micron laser pulses ranging from 0.8 J/cm 2 to 93 J/cm 2 . Gross examinations were done acutely and 24 hours after laser exposure. Skin biopsies were then collected at various times post exposure, and histologic examinations were conducted. Results: The 24 hour ED 50 was determined to be 4.5 J/cm 2 with fiducial limits of 6.2 and 2.2 J/cm 2 . As deposited energy was increased, the lesion presentation ranged from whitening of the epidermis (4 J/cm 2 ) to whitening with inflammatory centers (14 J/cm 2 ), and at the highest energy levels inflammatory areas were replaced with an epidermal ulcerated central area (>21 J/cm 2 ). Conclusion: Preliminary findings suggest pigmentation or melanin may play a minor role in the mechanism of laser-tissue damage. The ED 50 of Yorkshire pigs was 2.6 J/cm 2 . 3 The ED 50 of the Yucatan mini-pig was found to be 3.6 J/cm 2 , and although it was higher, it is still within the 95% fiducial limits.
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