Balance between Protection and Pathogenic Response to Aerosol Challenge with Mycobacterium tuberculosis (Mtb) in Mice Vaccinated with TriFu64, a Fusion Consisting of Three Mtb Antigens
| Autor: | Kawther Alqaseer, Andrea M. Cooper, Sadaf Sulman, Obolbek Turapov, Mrinal Kumar Das, Neda Nezam Abadi, Galina V. Mukamolova, M. Waheed Akhtar, Benjamin O Savidge, John E. Pearl |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Tuberculosis medicine.medical_treatment Immunology Disease Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Immune system antigen Antigen vaccine Drug Discovery medicine Pharmacology (medical) Pharmacology biology business.industry Pattern recognition receptor biology.organism_classification medicine.disease 030104 developmental biology Infectious Diseases tuberculosis Medicine weight loss Tuberculosis vaccines business Adjuvant 030215 immunology |
| Zdroj: | Vaccines, Vol 9, Iss 519, p 519 (2021) Vaccines Volume 9 Issue 5 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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