Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA).A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA.The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses.ClinicalTrials.gov NCT00057525

Viral hepatitis and agranulocytosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44381/1/10620_2005_Article_BF01071979.pd

Strengthening field-based training in low and middle-income countries to build public health capacity: Lessons from Australia's Master of Applied Epidemiology program

BACKGROUND: The International Health Regulations (2005) and the emergence and global spread of infectious diseases have triggered a re-assessment of how rich countries should support capacity development for communicable disease control in low and medium income countries (LMIC). In LMIC, three types of public health training have been tried: the university-based model; streamed training for specialised workers; and field-based programs. The first has low rates of production and teaching may not always be based on the needs and priorities of the host country. The second model is efficient, but does not accord the workers sufficient status to enable them to impact on policy. The third has the most potential as a capacity development measure for LMIC, but in practice faces challenges which may limit its ability to promote capacity development. DISCUSSION: We describe Australia's first Master of Applied Epidemiology (MAE) model (established in 1991), which uses field-based training to strengthen the control of communicable diseases. A central attribute of this model is the way it partners and complements health department initiatives to enhance workforce skills, health system performance and the evidence-base for policies, programs and practice. SUMMARY: The MAE experience throws light on ways Australia could collaborate in regional capacity development initiatives. Key needs are a shared vision for a regional approach to integrate training with initiatives that strengthen service and research, and the pooling of human, financial and technical resources. We focus on communicable diseases, but our findings and recommendations are generalisable to other areas of public health

Genetic polymorphisms and susceptibility to lung disease

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease