Safety and Immunogenicity of the ID93 + GLA-SE Tuberculosis Vaccine in BCG-Vaccinated Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.
GLA-SE
Immunogenicity
Safety
Subunit vaccine
Tuberculosis
Journal
Infectious diseases and therapy
ISSN: 2193-8229
Titre abrégé: Infect Dis Ther
Pays: New Zealand
ID NLM: 101634499
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
07
02
2023
accepted:
11
04
2023
medline:
11
5
2023
pubmed:
11
5
2023
entrez:
11
5
2023
Statut:
ppublish
Résumé
This randomized, double-blind, placebo-controlled, phase 2a trial was conducted to evaluate the safety and immunogenicity of the ID93 + glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) vaccine in human immunodeficiency virus (HIV)-negative, previously Bacillus Calmette-Guérin (BCG)-vaccinated, and QuantiFERON-TB-negative healthy adults in South Korea. Adults (n = 107) with no signs or symptoms of tuberculosis were randomly assigned to receive three intramuscular injections of 2 μg ID93 + 5 μg GLA-SE, 10 μg ID93 + 5 μg GLA-SE, or 0.9% normal saline placebo on days 0, 28, and 56. For safety assessment, data on solicited adverse events (AEs), unsolicited AEs, serious AEs (SAEs), and special interest AEs were collected. Antigen-specific antibody responses were measured using serum enzyme-linked immunosorbent assay. T-cell immune responses were measured using enzyme-linked immunospot and intracellular cytokine staining. No SAEs, deaths, or AEs leading to treatment discontinuation were found. The solicited local and systemic AEs observed were consistent with those previously reported. Compared with adults administered with the placebo, those administered with three intramuscular vaccine injections exhibited significantly higher antigen-specific antibody levels and Type 1 T-helper cellular immune responses. The ID93 + GLA-SE vaccine induced antigen-specific cellular and humoral immune responses, with an acceptable safety profile in previously healthy, BCG-vaccinated, Mycobacterium tuberculosis-uninfected adult healthcare workers. This clinical trial was retrospectively registered on 16 January 2019 at Clinicaltrials.gov (NCT03806686).
Identifiants
pubmed: 37166567
doi: 10.1007/s40121-023-00806-0
pii: 10.1007/s40121-023-00806-0
pmc: PMC10173211
doi:
Banques de données
ClinicalTrials.gov
['NCT03806686']
Types de publication
Journal Article
Langues
eng
Pagination
1605-1624Subventions
Organisme : Quratis Inc. and supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea
ID : HI14C1324
Informations de copyright
© 2023. The Author(s).
Références
World Health Organization. Tuberculosis (TB): fact sheets. 2022. https://www.who.int/news-room/fact-sheets/detail/tuberculosis . Accessed 30 Nov 2022.
Cohen A, Mathiasen VD, Schön T, Wejse C. The global prevalence of latent tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2019;54:1900655. https://doi.org/10.1183/13993003.00655-2019 .
doi: 10.1183/13993003.00655-2019
pubmed: 31221810
Korea Disease Control and Prevention Agency. Annual report on the notified tuberculosis patients in Korea 2019. 2020. http://www.kdca.go.kr/npt/biz/npp/portal/nppPblctDtaView.do?pblctDtaSeAt=1&pblctDtaSn=2088 . Accessed 30 Nov 2022.
Clemens JD, Chuong JJ, Feinstein AR. The BCG controversy. A methodological and statistical reappraisal. JAMA. 1983;249:2362–9. https://doi.org/10.1001/jama.1983.03330410048027 .
doi: 10.1001/jama.1983.03330410048027
pubmed: 6834635
Menzies R, Vissandjee B. Effect of bacille Calmette-Guérin vaccination on tuberculin reactivity. Am Rev Respir Dis. 1992;145:621–5. https://doi.org/10.1164/ajrccm/145.3.621 .
doi: 10.1164/ajrccm/145.3.621
pubmed: 1546843
Colditz GA, Berkey CS, Mosteller F, Brewer TF, Wilson ME, Burdick E, et al. The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics. 1995;96:29–35. https://doi.org/10.1542/peds.96.1.29 .
doi: 10.1542/peds.96.1.29
pubmed: 7596718
Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet. 1995;346:1339–45. https://doi.org/10.1016/s0140-6736(95)92348-9 .
doi: 10.1016/s0140-6736(95)92348-9
pubmed: 7475776
Woodworth JS, Clemmensen HS, Battey H, Dijkman K, Lindenstrøm T, Laureano RS, et al. A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette-Guérin. Nat Commun. 2021;12:6658. https://doi.org/10.1038/s41467-021-26934-0 .
doi: 10.1038/s41467-021-26934-0
pubmed: 34795205
pmcid: 8602668
Andersen P, Doherty TM. The success and failure of BCG—implications for a novel tuberculosis vaccine. Nat Rev Microbiol. 2005;3:656–62. https://doi.org/10.1038/nrmicro1211 .
doi: 10.1038/nrmicro1211
pubmed: 16012514
Anderson RC, Fox CB, Dutill TS, Shaverdian N, Evers TL, Poshusta GR, et al. Physicochemical characterization and biological activity of synthetic TLR4 agonist formulations. Colloids Surf B Biointerfaces. 2010;75:123–32. https://doi.org/10.1016/j.colsurfb.2009.08.022 .
doi: 10.1016/j.colsurfb.2009.08.022
pubmed: 19748238
Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, et al. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011;6:e16333. https://doi.org/10.1371/journal.pone.0016333 .
doi: 10.1371/journal.pone.0016333
pubmed: 21298114
pmcid: 3027669
Baldwin SL, Shaverdian N, Goto Y, Duthie MS, Raman VS, Evers T, et al. Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion. Vaccine. 2009;27:5956–63. https://doi.org/10.1016/j.vaccine.2009.07.081 .
doi: 10.1016/j.vaccine.2009.07.081
pubmed: 19679214
Lousada-Dietrich S, Jogdand PS, Jepsen S, Pinto VV, Ditlev SB, Christiansen M, et al. A synthetic TLR4 agonist formulated in an emulsion enhances humoral and Type 1 cellular immune responses against GMZ2–a GLURP-MSP3 fusion protein malaria vaccine candidate. Vaccine. 2011;29:3284–92. https://doi.org/10.1016/j.vaccine.2011.02.022 .
doi: 10.1016/j.vaccine.2011.02.022
pubmed: 21349366
Bertholet S, Goto Y, Carter L, Bhatia A, Howard RF, Carter D, et al. Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine. 2009;27:7036–45. https://doi.org/10.1016/j.vaccine.2009.09.066 .
doi: 10.1016/j.vaccine.2009.09.066
pubmed: 19786136
pmcid: 2783536
Bertholet S, Ireton GC, Ordway DJ, Windish HP, Pine SO, Kahn M, et al. A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med. 2010;2:53ra74. https://doi.org/10.1126/scitranslmed.3001094 .
doi: 10.1126/scitranslmed.3001094
pubmed: 20944089
pmcid: 3110937
Baldwin SL, Reese VA, Larsen SE, Beebe E, Guderian J, Orr MT, et al. Prophylactic efficacy against Mycobacterium tuberculosis using ID93 and lipid-based adjuvant formulations in the mouse model. PLoS One. 2021;16:e0247990. https://doi.org/10.1371/journal.pone.0247990 .
doi: 10.1371/journal.pone.0247990
pubmed: 33705411
pmcid: 7951850
Coler RN, Day TA, Ellis R, Piazza FM, Beckmann AM, Vergara J, et al. The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial. NPJ Vaccines. 2018;3:34. https://doi.org/10.1038/s41541-018-0057-5 .
doi: 10.1038/s41541-018-0057-5
pubmed: 30210819
pmcid: 6123489
Penn-Nicholson A, Tameris M, Smit E, Day TA, Musvosvi M, Jayashankar L, et al. Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. Lancet Respir Med. 2018;6:287–98. https://doi.org/10.1016/S2213-2600(18)30077-8 .
doi: 10.1016/S2213-2600(18)30077-8
pubmed: 29595510
Day TA, Penn-Nicholson A, Luabeya AKK, Fiore-Gartland A, Du Plessis N, Loxton AG, et al. Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial. Lancet Respir Med. 2021;9:373–86. https://doi.org/10.1016/S2213-2600(20)30319-2 .
doi: 10.1016/S2213-2600(20)30319-2
pubmed: 33306991
Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ, Raman VS, et al. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One. 2010;5:e13677. https://doi.org/10.1371/journal.pone.0013677 .
doi: 10.1371/journal.pone.0013677
pubmed: 21060869
pmcid: 2965144
Coler RN, Duthie MS, Hofmeyer KA, Guderian J, Jayashankar L, Vergara J, et al. From mouse to man: safety, immunogenicity and efficacy of a candidate leishmaniasis vaccine LEISH-F3+GLA-SE. Clin Transl Immunol. 2015;4:e35. https://doi.org/10.1038/cti.2015.6 .
doi: 10.1038/cti.2015.6
Singh K, Mukherjee P, Shakri AR, Singh A, Pandey G, Bakshi M, et al. Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial. NPJ Vaccines. 2018;3:48. https://doi.org/10.1038/s41541-018-0083-3 .
doi: 10.1038/s41541-018-0083-3
pubmed: 30302285
pmcid: 6162314
Santini-Oliveira M, Coler RN, Parra J, Veloso V, Jayashankar L, Pinto PM, et al. Schistosomiasis vaccine candidate Sm14/GLA-SE: Phase 1 safety and immunogenicity clinical trial in healthy, male adults. Vaccine. 2016;34:586–94. https://doi.org/10.1016/j.vaccine.2015.10.027 .
doi: 10.1016/j.vaccine.2015.10.027
pubmed: 26571311
Sirima SB, Richert L, Chêne A, Konate AT, Campion C, Dechavanne S, et al. PRIMVAC vaccine adjuvanted with alhydrogel or GLA-SE to prevent placental malaria: a first-in-human, randomised, double-blind, placebo-controlled study. Lancet Infect Dis. 2020;20:585–97. https://doi.org/10.1016/S1473-3099(19)30739-X .
doi: 10.1016/S1473-3099(19)30739-X
pubmed: 32032566
Field MJ, editor. Tuberculosis in the workplace. Washington (DC): National Academies Press; 2001.
Jung DH, Jo KW, Shim TS. Prevalence of latent tuberculosis infection among medical students in South Korea. Tuberc Respir Dis (Seoul). 2012;73:219–23. https://doi.org/10.4046/trd.2012.73.4.219 .
doi: 10.4046/trd.2012.73.4.219
pubmed: 23166557
Youakim S. The occupational risk of tuberculosis in a low-prevalence population. Occup Med (Lond). 2016;66:466–70. https://doi.org/10.1093/occmed/kqw040 .
doi: 10.1093/occmed/kqw040
pubmed: 27036151
Tendler M, Almeida MS, Vilar MM, Pinto PM, Limaverde-Sousa G. Current status of the Sm14/GLA-SE schistosomiasis vaccine: overcoming barriers and paradigms towards the first anti-parasitic human(itarian) vaccine. Trop Med Infect Dis. 2018;3:121. https://doi.org/10.3390/tropicalmed3040121 .
doi: 10.3390/tropicalmed3040121
pubmed: 30469320
pmcid: 6306874
Chung YK, Ahn YS, Jeong JS. Occupational infection in Korea. J Korean Med Sci. 2010;25:S53-61. https://doi.org/10.3346/jkms.2010.25.S.S53 .
doi: 10.3346/jkms.2010.25.S.S53
pubmed: 21258592
pmcid: 3023352
Joint committee for the revision of Korean guidelines for tuberculosis. Korean guidelines for tuberculosis. 2nd ed. Cheongju: Korea Centers for Disease Control & Prevention; 2016