DNA vaccines might offer an alternative to the live smallpox vaccine in providing protective efficacy in an orthopoxvirus (OPV) lethal respiratory challenge model. BALB/c mice were immunised with DNA vaccines coding for 10 different single vaccinia virus (VACV) membrane proteins. After an intranasal challenge with the VACV IHD strain, three gene candidates B5R, A33R and A27L produced ≥66% survival. The B5R DNA vaccine consistently produced 100% protection and exhibited greatest efficacy after three 50 g intramuscular doses in this model. Sero-conversion to these vaccines was often inconsistent, implying that antibody itself was not a correlate of protection. The B5R DNA vaccine induced a strong and consistent gamma interferon (IFN␥) response in BALB/c mice given a single DNA vaccine dose. Strong IFN␥ responses were also measured in pTB5R immunised C57BL6 mice deficient for MHC class I molecules, suggesting that the memory response was mediated by a CD4 + T cell population. Crown

Presently there is a significant effort to develop and evaluate vaccines and antibiotics against the potential bioterrorism agent Yersinia pestis. The animal models used to test these countermeasures involve the deposition of small particles within the lung. However, deliberate aerosol release of Y. pestis will generate both small and large inhalable particles. We report in this study that the pathogenesis patterns of plague infections caused by the deposition of 1-and 12-m-particle aerosols of Y. pestis in the lower and upper respiratory tracts (URTs) of mice are different. The median lethal dose for 12-m particles was 4.9-fold greater than that for 1-m particles. The 12-m-particle infection resulted in the degradation of the nasal mucosa and nasal-associated lymphoid tissue (NALT) plus cervical lymphadenopathy prior to bacteremic dissemination. Lung involvement was limited to secondary pneumonia. In contrast, the 1-m-particle infection resulted in primary pneumonia; in 40% of mice, the involvement of NALT and cervical lymphadenopathy were observed, indicating entry via both URT lymphoid tissues and lungs. Despite bacterial deposition in the gastrointestinal tract, the involvement of Peyer's patches was not observed in either infection. Although there were major differences in pathogenesis, the recombinant F1 and V antigen vaccine and ciprofloxacin protected against plague infections caused by small-and large-particle aerosols.In humans, Yersinia pestis infections present clinically as bubonic, septicemic, and pneumonic plague. The introduction of Y. pestis into the bloodstream by flea bites results in the characteristic lymphadenopathy of bubonic plague. Lymphatic and circulatory dissemination causes hematogenous seeding of the lungs, producing secondary pneumonia. Primary pneumonic plague arises from the inhalation of aerosols containing Y. pestis. Both bubonic and primary pneumonic plague can progress to septicemia, resulting in endotoxic shock during the terminal stages of infection (26,29). There is currently a high level of interest in biodefense models of airborne diseases for the identification of virulence mechanisms and the testing of medical countermeasures. The focus is on the pneumonic forms of these diseases caused by the inhalation of smallparticle aerosols.Over the past decade, and in the context of the possible use of Y. pestis in bioterrorism, there has been significant interest in devising therapeutics for pneumonic plague. Antibiotics including tetracyclines, streptomycin, and chloramphenicol are used to treat pneumonic plague (5, 44). Recently, the broadspectrum fluoroquinolone antibiotic ciprofloxacin has been proposed for postexposure prophylaxis for mass-casualty-setting plague (26). Ciprofloxacin possesses excellent pharmacokinetic properties, with high lung concentrations providing efficacy against murine pneumonic plague (11, 41, 42). Significant progress in the development of plague vaccines has been made. Vaccines containing F1 capsular polypeptide and LcrV (V) antigens protect agai...

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SUMMARYIn this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-l"*" individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 10* cells was 391 for PBL, with a range of 1 -9000, and 2971 for BAL cells, with a range of < 1-70000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by cocultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy.

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