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Sulman S, Savidge BO, Alqaseer K, et al. Balance between Protection and Pathogenic Response to Aerosol Challenge with . Vaccines (Basel). 2021;9(5)doi: 10.3390/vaccines9050519.
Sulman, S., Savidge, B. O., Alqaseer, K., Das, M. K., Nezam Abadi, N., Pearl, J. E., Turapov, O., Mukamolova, G. V., Akhtar, M. W., & Cooper, A. M. (2021). Balance between Protection and Pathogenic Response to Aerosol Challenge with . Vaccines, 9(5), . https://doi.org/10.3390/vaccines9050519
Sulman, Sadaf, et al. "Balance between Protection and Pathogenic Response to Aerosol Challenge with ." Vaccines vol. 9,5 (2021). doi: https://doi.org/10.3390/vaccines9050519
Sulman S, Savidge BO, Alqaseer K, Das MK, Nezam Abadi N, Pearl JE, Turapov O, Mukamolova GV, Akhtar MW, Cooper AM. Balance between Protection and Pathogenic Response to Aerosol Challenge with . Vaccines (Basel). 2021 May 18;9(5). doi: 10.3390/vaccines9050519. PMID: 34070048; PMCID: PMC8158147.
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Vaccines (Basel). 2021 May 18;9(5). doi: 10.3390/vaccines9050519.

Balance between Protection and Pathogenic Response to Aerosol Challenge with .

Vaccines

Sadaf Sulman, Benjamin O Savidge, Kawther Alqaseer, Mrinal K Das, Neda Nezam Abadi, John E Pearl, Obolbek Turapov, Galina V Mukamolova, M Waheed Akhtar, Andrea May Cooper

Affiliations

  1. Department Respiratory Sciences, University of Leicester, Leicester LE1 7RH, UK.
  2. School of Biological Sciences, University of the Punjab, Lahore 54590, Pakistan.
  3. Leicester Tuberculosis Research Group-LTBRG, University of Leicester, Leicester LE1 7RH, UK.
  4. Department of Basic Science, Faculty of Nursing, University of Kufa, P.O. Box 21, Kufa, Najaf Governorate, Najaf 540011, Iraq.
  5. APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.

PMID: 34070048 PMCID: PMC8158147 DOI: 10.3390/vaccines9050519

Abstract

Tuberculosis vaccines capable of reducing disease worldwide have proven difficult to develop. BCG is effective in limiting childhood disease, but adult TB is still a major public health issue. Development of new vaccines requires identification of antigens that are both spatially and temporally available throughout infection, and immune responses to which reduce bacterial burden without increasing pathologic outcomes. Subunit vaccines containing antigen require adjuvants to drive appropriate long-lived responses. We generated a triple-antigen fusion containing the virulence-associated EsxN (Rv1793), the PPE42 (Rv2608), and the latency associated Rv2628 to investigate the balance between bacterial reduction and weight loss in an animal model of aerosol infection. We found that in both a low pattern recognition receptor (PRR) engaging adjuvant and a high PRR-engaging adjuvant (MPL/TDM/DDA) the triple-antigen fusion could reduce the bacterial burden, but also induced weight loss in the mice upon aerosol infection. The weight loss was associated with an imbalance between TNFα and IL-17 transcription in the lung upon challenge. These data indicate the need to assess both protective and pathogenic responses when investigating subunit vaccine activity.

Keywords: antigen; tuberculosis; vaccine; weight loss

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