Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

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Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

Vaccines ◽

10.3390/vaccines9040394 ◽

2021 ◽

Vol 9 (4) ◽

pp. 394

Author(s):

Mariia Sergeeva ◽

Ekaterina Romanovskaya-Romanko ◽

Natalia Zabolotnyh ◽

Anastasia Pulkina ◽

Kirill Vasilyev ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Vaccine Candidate ◽

Cell Immune Response ◽

Lung Pathology ◽

Ns1 Protein ◽

Reading Frame ◽

Intranasal Immunization ◽

Vector Vaccine ◽

Boost Immunization ◽

New Strategies

New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv.

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Cellular immune response in MDR-TB patients to different protein expression of MDR and susceptible Mycobacterium tuberculosis: Rv0147, a novel MDR-TB biomarker

Immunologic Research ◽

10.1007/s12026-017-8971-6 ◽

2017 ◽

Vol 66 (1) ◽

pp. 59-66 ◽

Cited By ~ 1

Author(s):

Alireza Hadizadeh Tasbiti ◽

Shamsi Yari ◽

Seyed Davar Siadat ◽

Payam Tabarsi ◽

Kayvan Saeedfar ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Protein Expression ◽

Cellular Immune Response ◽

Mdr Tb ◽

Cellular Immune

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Cellular immune response to Mycobacterium tuberculosis-specific antigen culture filtrate protein-10 in south India

Medical Microbiology and Immunology ◽

10.1007/s00430-009-0129-2 ◽

2009 ◽

Vol 199 (1) ◽

pp. 11-25 ◽

Cited By ~ 5

Author(s):

Madhan Kumar ◽

Jagadish C. Sundaramurthi ◽

Narinder K. Mehra ◽

Gurvinder Kaur ◽

Alamelu Raja

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Culture Filtrate ◽

Cellular Immune Response ◽

South India ◽

Specific Antigen ◽

Cellular Immune ◽

Culture Filtrate Protein

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Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

10.1101/2021.09.05.21263125 ◽

2021 ◽

Author(s):

Michael Bonelli ◽

Daniel Mrak ◽

Selma Tobudic ◽

Daniela Sieghart ◽

Maximilian Koblischke ◽

...

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

Controlled Trial ◽

Seroconversion Rate ◽

Booster Vaccination ◽

Serious Adverse Events ◽

Vector Vaccine ◽

Vector Versus ◽

Immunosuppressed Patients ◽

Cellular Immune

ABSTRACTSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID-19 vaccination. In this blinded randomized clinical trial (EudraCT 2021-002348-57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non-seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV-19 (Oxford-AstraZeneca). Patients were stratified according to the presence of peripheral B-cells. The primary efficacy endpoint was the difference in the SARS-CoV-2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four.Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T-cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non-seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

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Use of novel adjuvants and delivery systems to improve the humoral and cellular immune response to malaria vaccine candidate antigens

Vaccine ◽

10.1016/0264-410x(93)90239-t ◽

1993 ◽

Vol 11 (5) ◽

pp. 591-593 ◽

Cited By ~ 16

Author(s):

Daniel M. Gordon

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Delivery Systems ◽

Malaria Vaccine Candidate ◽

Cellular Immune

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Induction of cellular immune response and anti-Salmonella enterica serovar typhi bactericidal antibodies in healthy volunteers by immunization with a vaccine candidate against typhoid fever

Immunology Letters ◽

10.1016/j.imlet.2004.01.010 ◽

2004 ◽

Vol 93 (2-3) ◽

pp. 115-122 ◽

Cited By ~ 33

Author(s):

Rosa Marı́a Salazar-González ◽

Carmen Maldonado-Bernal ◽

Nora Elena Ramı́rez-Cruz ◽

Nora Rios-Sarabia ◽

Jorge Beltrán-Nava ◽

...

Keyword(s):

Immune Response ◽

Typhoid Fever ◽

Healthy Volunteers ◽

Cellular Immune Response ◽

Salmonella Enterica ◽

Vaccine Candidate ◽

Salmonella Enterica Serovar Typhi ◽

Cellular Immune

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Host genetic background affects regulatory T‐cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis

Immunology and Cell Biology ◽

10.1038/icb.2010.116 ◽

2010 ◽

Vol 89 (4) ◽

pp. 526-534 ◽

Cited By ~ 16

Author(s):

Marina Oliveira Paula ◽

Denise Morais Fonseca ◽

Pryscilla Fanini Wowk ◽

Ana Flávia Gembre ◽

Paola Fernanda Fedatto ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

T Cell ◽

Regulatory T Cell ◽

Cellular Immune Response ◽

Genetic Background ◽

Cell Activity ◽

Host Genetic ◽

Cellular Immune

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Ub Combination Enhanced Cellular Immune Response Elicited by HSP65 DNA Vaccine against <i>Mycobacterium tuberculosis</i>

World Journal of Vaccines ◽

10.4236/wjv.2013.33013 ◽

2013 ◽

Vol 03 (03) ◽

pp. 89-97 ◽

Cited By ~ 1

Author(s):

Qingmin Wang ◽

Chengxiang Lei ◽

Qiuhong Liu

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Dna Vaccine ◽

Cellular Immune Response ◽

Cellular Immune

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Immunosequencing and epitope mapping reveal substantial preservation of the T cell immune response to Omicron generated by SARS-CoV-2 vaccines

10.1101/2021.12.20.21267877 ◽

2021 ◽

Author(s):

Damon H. May ◽

Benjamin E. R. Rubin ◽

Sudeb C. Dalai ◽

Krishna Patel ◽

Shahin Shafiani ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Cellular Immune Response ◽

Epitope Mapping ◽

Protective Efficacy ◽

T Cell Response ◽

Cell Immune Response ◽

Cell Immunity ◽

Cellular Immune

The Omicron SARS-CoV-2 variant contains 34 mutations in the spike gene likely impacting protective efficacy from vaccines. We evaluated the potential impact of these mutations on the cellular immune response. Combining epitope mapping to SARS-CoV-2 vaccines that we have determined from past experiments along with T cell receptor (TCR) repertoire sequencing from thousands of vaccinated or naturally infected individuals, we estimate the abrogation of the cellular immune response in Omicron. Although 20% of CD4+ T cell epitopes are potentially affected, the loss of immunity mediated by CD4+ T cells is estimated to be slightly above 30% as some of the affected epitopes are relatively more immunogenic. For CD8+ T cells, we estimate a loss of approximately 20%. These reductions in T cell immunity are substantially larger than observed in other widely distributed variants. Combined with the expected substantial loss of neutralization from antibodies, the overall protection provided by SARS-CoV-2 vaccines could be impacted adversely. From analysis of prior variants, the efficacy of vaccines against symptomatic infection has been largely maintained and is strongly correlated with the T cell response but not as strongly with the neutralizing antibody response. We expect the remaining 70% to 80% of on-target T cells induced by SARS-CoV-2 vaccination to reduce morbidity and mortality from infection with Omicron.

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