Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis
IntroductionThe inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we a...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1492268/full |
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| author | Jin-Seung Yun Jin-Seung Yun Eunkyung Shin Young-Ran Lee Jung-Ah Lee Hyeokjin Lee Jong-Seok Kim Sung Jae Shin Sang-Jun Ha Sang-Won Lee Dokeun Kim Jung-Sik Yoo Hye-Sook Jeong |
| author_facet | Jin-Seung Yun Jin-Seung Yun Eunkyung Shin Young-Ran Lee Jung-Ah Lee Hyeokjin Lee Jong-Seok Kim Sung Jae Shin Sang-Jun Ha Sang-Won Lee Dokeun Kim Jung-Sik Yoo Hye-Sook Jeong |
| author_sort | Jin-Seung Yun |
| collection | DOAJ |
| description | IntroductionThe inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against Mycobacterium tuberculosis.MethodsWe constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of M. tuberculosis (rAd-TB4), immunized with rAd-TB4 (5 × 107 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route.ResultsCompared with the BCG-only (2 × 105 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 107 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization (p < 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway.ConclusionOur results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate. |
| format | Article |
| id | doaj-art-80922bff88d240808212f98495a24d20 |
| institution | Kabale University |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj-art-80922bff88d240808212f98495a24d202025-01-24T07:13:33ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011610.3389/fmicb.2025.14922681492268Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosisJin-Seung Yun0Jin-Seung Yun1Eunkyung Shin2Young-Ran Lee3Jung-Ah Lee4Hyeokjin Lee5Jong-Seok Kim6Sung Jae Shin7Sang-Jun Ha8Sang-Won Lee9Dokeun Kim10Jung-Sik Yoo11Hye-Sook Jeong12Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaBio-Convergence R&D Division, Korea Institute of Ceramic Engineering and Technology, Cheongju, Chungbuk, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaKorea Disease Control and Prevention Agency, Cheongju, Republic of KoreaDepartment of Cell Biology, College of Medicine, Myunggok Medical Research Institute, Konyang University, Daejeon, Republic of KoreaDepartment of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Republic of KoreaDepartment of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of KoreaKorea Disease Control and Prevention Agency, Cheongju, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaKorea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Republic of KoreaIntroductionThe inadequate efficacy of the Bacillus Calmette–Guérin (BCG) vaccine against adult pulmonary tuberculosis (TB) necessitates the development of new and effective vaccines. Human adenovirus serotype 5 (Ad5), which induces T-cell response, is a widely used viral vector. In this study, we aimed to evaluate the efficacy of a multi-antigenic recombinant Ad5 vectored vaccine and determine the optimal immunization route for enhanced immune response against Mycobacterium tuberculosis.MethodsWe constructed a multi-antigenic recombinant Ad5 vectored vaccine expressing four antigens (Ag85B-ESAT6-MPT64-Rv2660c) of M. tuberculosis (rAd-TB4), immunized with rAd-TB4 (5 × 107 infectious virus units/mouse) twice at an interval of 4 weeks starting at 10 weeks after BCG priming, and evaluated its boosting efficacy in a BCG-primed mouse model, and determined the optimal immunization route.ResultsCompared with the BCG-only (2 × 105 colony forming units/mouse), subcutaneous injection of rAd-TB4 (1 × 107 infectious virus units/mL; two doses) elicited a T-cell response and cytokine production in lung lymphocytes and splenocytes. rAd-TB4 immunization significantly reduced bacterial loads and inflamed lung areas compared to BCG immunization (p < 0.01) and protected against the H37Rv challenge performed at 17 weeks of BCG priming. RNA sequencing of the whole blood of rAd-TB4-vaccinated mice collected pre- and, 1 and 4 weeks post-infection, identified differentially expressed genes associated with immune and inflammatory responses, especially those in the Wnt signaling pathway.ConclusionOur results indicate that rAd-TB4 immunization enhances the immune response to the vaccine boosting antigens in BCG-primed mice, making it a potential adult pulmonary TB vaccine candidate.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1492268/fullpulmonary tuberculosisBCG vaccineadenovirus vectormulti-antigenic vaccineimmunizationmouse model |
| spellingShingle | Jin-Seung Yun Jin-Seung Yun Eunkyung Shin Young-Ran Lee Jung-Ah Lee Hyeokjin Lee Jong-Seok Kim Sung Jae Shin Sang-Jun Ha Sang-Won Lee Dokeun Kim Jung-Sik Yoo Hye-Sook Jeong Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis Frontiers in Microbiology pulmonary tuberculosis BCG vaccine adenovirus vector multi-antigenic vaccine immunization mouse model |
| title | Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis |
| title_full | Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis |
| title_fullStr | Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis |
| title_full_unstemmed | Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis |
| title_short | Immunogenicity and protective efficacy of a multi-antigenic adenovirus-based vaccine candidate against Mycobacterium tuberculosis |
| title_sort | immunogenicity and protective efficacy of a multi antigenic adenovirus based vaccine candidate against mycobacterium tuberculosis |
| topic | pulmonary tuberculosis BCG vaccine adenovirus vector multi-antigenic vaccine immunization mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1492268/full |
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