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Volume 9
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Article

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

by
Sadaf Sulman
1,2,
Benjamin O. Savidge
1,3,
Kawther Alqaseer
1,3,4,
Mrinal K. Das
1,3,
Neda Nezam Abadi
1,5,
John E. Pearl
1,3,
Obolbek Turapov
1,3,
Galina V. Mukamolova
1,3,
M. Waheed Akhtar
2 and
Andrea May Cooper
1,3,*
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
*
Author to whom correspondence should be addressed.
Vaccines 2021, 9(5), 519; https://doi.org/10.3390/vaccines9050519
Submission received: 19 April 2021 / Revised: 13 May 2021 / Accepted: 15 May 2021 / Published: 18 May 2021
(This article belongs to the Special Issue Vaccines for Infectious and Chronic Diseases)
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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: tuberculosis; vaccine; antigen; weight loss tuberculosis; vaccine; antigen; weight loss

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MDPI and ACS Style

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. 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. Vaccines 2021, 9, 519. https://doi.org/10.3390/vaccines9050519

AMA Style

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 Mycobacterium tuberculosis (Mtb) in Mice Vaccinated with TriFu64, a Fusion Consisting of Three Mtb Antigens. Vaccines. 2021; 9(5):519. https://doi.org/10.3390/vaccines9050519

Chicago/Turabian Style

Sulman, Sadaf, Benjamin O. Savidge, Kawther Alqaseer, Mrinal K. Das, Neda Nezam Abadi, John E. Pearl, Obolbek Turapov, Galina V. Mukamolova, M. Waheed Akhtar, and Andrea May Cooper. 2021. "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" Vaccines 9, no. 5: 519. https://doi.org/10.3390/vaccines9050519

APA Style

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 Mycobacterium tuberculosis (Mtb) in Mice Vaccinated with TriFu64, a Fusion Consisting of Three Mtb Antigens. Vaccines, 9(5), 519. https://doi.org/10.3390/vaccines9050519

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