Baillie L., Trapaidze N., Doğanay M., Ingram R.
NATO Destekli Araştırma Projesi, 2013 - 2017
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Proje Türü:
NATO Destekli Araştırma Projesi
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Başlama Tarihi:
Eylül 2013
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Bitiş Tarihi:
Şubat 2017
Proje Özeti
Abstract
Currently the majority of the world’s population is susceptible to infection with anthrax. Indeed the US postal attacks in 2001 highlighted the vulnerability of the civilian population and brought home the need to develop effective, rapid, robust medical countermeasures against the threat posed by terrorist use of this organism. The results from this study confirmed that cutaneous infection with B.anthracis stimulates the production of PA, LF and EF specific IgG antibodies. In the majority of cases the antibody response to PA was the strongest followed by LF and EF. While the overall pattern of the responses of the Georgian and Turkish patients was broadly similar we did observed statistically significant differences in the mean antibody titres of infected individuals from the Van region of Turkey. This group responded relatively poorly to PA compared to the other groups but mounted a robust antibody response to LF. We also observed a gender specific difference in the responses in this group of individuals in that Anti-PA antibodies were detectable earlier in males (p = 0.007) and the maximal antibody titre was significantly higher (p = 0.03). These results differed from those observed in AVA immunised individuals were females mounted the highest anti-PA IgG responses (Pondo T., et al., (2014) Vaccine;32:3548–3554). We also observed gender specific differences in cytokine responses during the early stages of infection. Males had significantly higher circulating levels of the pro-inflammatory cytokine IL-17F (p = 0.005) and of TGF-β (p = 0.04). It may be that the results from the Van cohort reflect differences in cultural and behavioral activities between the sexes which result in disparate levels of exposure to anthrax. Alternatively, exposure in the complex context of natural infection may result in distinct outcomes compared to antigen exposure in the context of vaccination. To our knowledge this is first evidence that the sex of an infected human influences their ability to mount a protective immune response. These observations warrant further investigation in larger cohorts as understanding the role of gender in susceptibility may help to elucidate the mechanisms of optimal natural protection. They also suggests that not every population will mount a similar immune response when exposed to the pathogen which could have important implications when attempting to design a sub-unit vaccine capable of protecting all members of a population. The outputs of this work will contribute to the development of future vaccines which will confer broad-spectrum, robust protection following minimal dosing. Access to such vaccines would contribute to the protection of citizens of NATO and partner countries against the bioterrorist use of anthrax.