Novel Multistage Subunit Mycobacterium tuberculosis Nanoparticle Vaccine Confers Protection Against Experimental Infection in Prophylactic and Therapeutic Regimens. / Tukhvatulin, Amir I.; Dzharullaeva, Alina S.; Vasina, Daria V. et al.
In: Vaccines, Vol. 14, No. 1, 5, 2026.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Novel Multistage Subunit Mycobacterium tuberculosis Nanoparticle Vaccine Confers Protection Against Experimental Infection in Prophylactic and Therapeutic Regimens
AU - Tukhvatulin, Amir I.
AU - Dzharullaeva, Alina S.
AU - Vasina, Daria V.
AU - Fursov, Mikhail V.
AU - Izhaeva, Fatima M.
AU - Kleymenov, Denis A.
AU - Shcherbinin, Dmitry N.
AU - Polyakov, Nikita B.
AU - Solovyev, Andrey I.
AU - Zhukhovitsky, Vladimir G.
AU - Zhitkevich, Alla S.
AU - Gordeychuk, Ilya V.
AU - Litvinova, Anna M.
AU - Manuylov, Victor A.
AU - Potapov, Vasiliy D.
AU - Tkachuk, Artem P.
AU - Gushchin, Vladimir A.
AU - Logunov, Denis Y.
AU - Gintsburg, Alexander L.
N1 - This study was conducted with the support of the Ministry of Education and Science of Russia within the framework of the Federal Targeted Program Pharma-2020 (State Contract No. 14.N08.11.0192 dated 22 November 2017) and the State Assignment of the Ministry of Health of Russia No. 125020501441-9. TEM was conducted at the Chumakov FSC R&D IBP RAS (Institute of Poliomyelitis) as part of fundamental research assignment No. 426.
PY - 2026
Y1 - 2026
N2 - Background/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization’s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular/nasal prime-boost regimen, the vaccine elicited a mixed Th1/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control.
AB - Background/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization’s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular/nasal prime-boost regimen, the vaccine elicited a mixed Th1/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control.
KW - Mycobacterium tuberculosis
KW - TB
KW - multi-stage vaccines
KW - subunit vaccines
KW - pattern-recognition receptors
KW - PRR agonists
UR - https://www.scopus.com/pages/publications/105029118605
UR - https://www.mendeley.com/catalogue/f469a02f-c2c8-3923-b1e1-29c32fa5d148/
U2 - 10.3390/vaccines14010005
DO - 10.3390/vaccines14010005
M3 - Article
C2 - 41600921
VL - 14
JO - Vaccines
JF - Vaccines
SN - 2076-393X
IS - 1
M1 - 5
ER -
ID: 76409536