Leduc, IsabelleFortney, Kate R.Janowicz, Diane M.Zwickl, BethEllinger, SheilaKatz, Barry P.Lin, HuaiyingDong, QunfengSpinola, Stanley M.2020-03-172020-03-172019-07Leduc, I., Fortney, K. R., Janowicz, D. M., Zwickl, B., Ellinger, S., Katz, B. P., ... & Spinola, S. M. (2019). A class I Haemophilus ducreyi strain containing a class II hgbA allele is partially attenuated in humans: implications for HgbA vaccine efficacy trials. Infection and immunity, 87(7), e00112-19. 10.1128/IAI.00112-190019-9567, 1098-5522https://hdl.handle.net/1805/22342Haemophilus ducreyi causes chancroid and is a major cause of cutaneous ulcers in children. Due to environmental reservoirs, both class I and class II H. ducreyi strains persist in cutaneous ulcer regions of endemicity following mass drug administration of azithromycin, suggesting the need for a vaccine. The hemoglobin receptor (HgbA) is a leading vaccine candidate, but its efficacy in animal models is class specific. Controlled human infection models can be used to evaluate vaccines, but only a class I strain (35000HP) has been characterized in this model. As a prelude to evaluating HgbA vaccines in the human model, we tested here whether a derivative of 35000HP containing a class II hgbA allele (FX548) is as virulent as 35000HP in humans. In eight volunteers infected at three sites with each strain, the papule formation rate was 95.8% for 35000HP versus 62.5% for FX548 (P = 0.021). Excluding doses of FX548 that were ≥2-fold higher than those of 35000HP, the pustule formation rate was 25% for 35000HP versus 11.7% for FX548 (P = 0.0053). By Western blot analysis, FX548 and 35000HP expressed equivalent amounts of HgbA in whole-cell lysates and outer membranes. The growth of FX548 and 35000HP was similar in media containing hemoglobin or hemin. By whole-genome sequencing and single-nucleotide polymorphism analysis, FX548 contained no mutations in open reading frames other than hgbA. We conclude that by an unknown mechanism, FX548 is partially attenuated in humans and is not a suitable strain for HgbA vaccine efficacy trials in the model.en-USPublisher PolicyHaemophilus ducreyiHemoglobinVaccinesArticle