Lung memory T-cell response in mice following intranasal immunization with influenza vector expressing mycobacterial proteins

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Abstract

Improving specific prevention of tuberculosis continues to be a top priority in phthisiology. “Prime-boost” vaccination schemes aim to maintain adequate levels of specific immunity while forming long-term protection. They are based on sequential use of BCG vaccine and new vaccine candidates expressing protective mycobacterial proteins. The development of new tuberculosis prevention approaches requires an understanding of how the anti-tuberculosis immune response forms and which mechanisms provide TB protection. Since tuberculosis is an airborne infection, vaccine effectiveness largely depends on mucosal immunity based on the formation of long-lived, functionally-active memory T-lymphocytes in the respiratory tract. We have previously shown that the influenza vector expressing ESAT-6 and Ag85A mycobacterial proteins (Flu/ESAT-6_Ag85A) in vaccination scheme of intranasal boost immunization resulted in significant increase of BCG's protective effect according to key indicators aggregate data in experimental tuberculosis infection. The aim of this work was to study the effect of intranasal immunization with the Flu/ESAT-6_Ag85A influenza vector on the formation of antigen-specific central and effector memory T cells and the cytokine-producing activity of effector T cells (TEM) in BCG standard and “BCG prime — influenza vector boost” vaccination schemes in mice. Intranasal immunization with the influenza vector has been shown to increase the proportion of antigen-specific CD4+ central memory T cells (TCM) in the pool of activated lymphocytes of lung and spleen reaching significant differences from the BCG group in the percentage of spleen CD4+ TCM (p < 0.01). In contrast to BCG, vaccination with the studied vaccine candidate was accompanied by accumulation of highly differentiated CD8 effector cells in lung, the target organ during tuberculosis infection. Comparative evaluation of the cell-mediated, post-vaccine immune response after immunization with influenzavector-based vaccine candidate (intranasal/mucosal) or BCG vaccine (subcutaneous) showed advantages in the mucosal group: in formation of functionally active subpopulations of effector CD4 and CD8 T lymphocytes (CD44highCD62Llow) in lungs secreting IL-2 as well as polyfunctional cells capable of coproducing two cytokines (IFNγ/TNFα or IFNγ/IL-2) or three cytokines (IFNγ/TNFα/IL-2). Due to their more pronounced effector function, polyfunctional T-lymphocytes can be considered to be potential immunological markers of protective immunity in tuberculosis.

About the authors

A.-P. S. Shurygina

Smorodintsev Research Institute of Influenza Russian Ministry of Health

Email: ann-polin@yandex.ru
ORCID iD: 0000-0003-3685-7068

Schurygina Anna-Polina S., PhD (Medicine), Senior Researcher, Laboratory of Vectored Vaccine

St. Petersburg

Russian Federation

N. V. Zabolotnykh

Saint-Petersburg State Research Institute of Phthisiopulmonology Russian Ministry of Health

Email: zabol-natal@yandex.ru
ORCID iD: 0000-0002-2946-2415

Zabolotnykh Natalia V., PhD, MD (Medicine), Leading Researcher of the “Experimental Tuberculosis and Innovative Technologies” Direction

St. Petersburg

Russian Federation

T. I. Vinogradova

Saint-Petersburg State Research Institute of Phthisiopulmonology Russian Ministry of Health

Email: vinogradova@spbniif.ru
ORCID iD: 0000-0002-5234-349X

Vinogradova Tatiana I., PhD, MD (Medicine), Head Researcher of the “Experimental Tuberculosis and Innovative Technologies” Direction

St. Petersburg

Russian Federation

K. A. Vasilyev

Smorodintsev Research Institute of Influenza Russian Ministry of Health

Email: kirillv5@yandex.ru
ORCID iD: 0000-0002-7750-9652

Vasiliev Kirill А., Researcher, Laboratory of Vectored Vaccine

St. Petersburg

Russian Federation

Zh. V. Buzitskaya

Smorodintsev Research Institute of Influenza Russian Ministry of Health

Email: janna.buzitskaya@influenza.spb.ru
ORCID iD: 0000-0002-8394-102X

Buzitskaya Zhanna V., PhD (Medicine), Senior Researcher, Laboratory of Vectored Vaccine

St. Petersburg

Russian Federation

M. A. Stukova

Smorodintsev Research Institute of Influenza Russian Ministry of Health

Author for correspondence.
Email: marina.stukova@influenza.spb.ru
ORCID iD: 0000-0002-2127-3820

Stukova Marina A., PhD (Medicine), Head of the Laboratory of Vectored Vaccine

197376, St. Petersburg, Prof. Popova str., 15/17

Russian Federation

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Copyright (c) 2020 Shurygina A.S., Zabolotnykh N.V., Vinogradova T.I., Vasilyev K.A., Buzitskaya Z.V., Stukova M.A.

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