An Update on Tuberculosis Vaccines.

Animals Antigens, Bacterial BCG Vaccine HIV Infections Mycobacterium tuberculosis / immunology Tuberculosis / prevention & control Tuberculosis Vaccines
Adjuvant Clinical trial M. vaccae MTBVAC Subunit vaccine Tuberculosis VPM1002 Vaccines Viral vectors

Journal

Methods in molecular biology (Clifton, N.J.)
ISSN: 1940-6029
Titre abrégé: Methods Mol Biol
Pays: United States
ID NLM: 9214969

Informations de publication

Date de publication:
2022
Historique:
entrez: 16 12 2021
pubmed: 17 12 2021
medline: 27 1 2022
Statut: ppublish

Résumé

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading cause of mortality and morbidity due to a single infectious agent. Aerosol infection with Mtb can result in a range of responses from elimination, active, incipient, subclinical, and latent Mtb infections (LTBI), depending on the host's immune response and the dose and nature of infecting bacilli. Currently, BCG is the only vaccine approved to prevent TB. Although BCG confers protection against severe forms of childhood TB, its use in adults and those with comorbid conditions, such as HIV infection, is questionable. Novel vaccines, including recombinant BCG (rBCG), were developed to improve BCG's efficacy and use as an alternative to BCG in a vulnerable population. The first-generation rBCG vaccines had different Mtb antigens and were tested as a prime, prime-boost, or immunotherapeutic intervention. The novel vaccines target one or more of the following requirements, namely prevention of infection (POI), prevention of disease (POD), prevention of recurrence (POR), and therapeutic vaccines to treat a TB disease. Several vaccine candidates currently in development are classified into four primary categories: live attenuated whole-cell vaccine, inactivated whole-cell vaccine, adjuvanted protein subunit vaccine, and viral-vectored vaccine. Each vaccine's immunogenicity, safety, and efficacy are tested in preclinical animal models and further validated through various phases of clinical trials. This chapter summarizes the various TB vaccine candidates under different clinical trial stages and promises better protection against TB.

Identifiants

DOI: 10.1007/978-1-0716-1884-4_20 PMID: 34914059
pubmed: 34914059
doi: 10.1007/978-1-0716-1884-4_20
doi:

Substances chimiques

Antigens, Bacterial 0
BCG Vaccine 0
Tuberculosis Vaccines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

387-409

Informations de copyright

© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.

Références

WHO (2019) Global tuberculosis report 2019. https://www.who.int/tb/publications/global_report/en/
WHO (2015) End TB strategy. The World Health Organization, Geneva, Switzerland.  https://www.who.int/teams/global-tuberculosis-programme/the-end-tb-strategy#
Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, Fineberg HV et al (1994) Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 271(9):698–702
doi: 10.1001/jama.1994.03510330076038
Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE et al (2014) Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis 58(4):470–480. https://doi.org/10.1093/cid/cit790
doi: 10.1093/cid/cit790 pubmed: 24336911
Mendez-Samperio P (2019) Current challenges and opportunities for bacillus Calmette-Guerin replacement vaccine candidates. Scand J Immunol 90(4):e12772. https://doi.org/10.1111/sji.12772
doi: 10.1111/sji.12772 pubmed: 31055842
Zwerling A, Behr MA, Verma A, Brewer TF, Menzies D, Pai M (2011) The BCG world atlas: a database of global BCG vaccination policies and practices. PLoS Med 8(3):e1001012. https://doi.org/10.1371/journal.pmed.1001012
doi: 10.1371/journal.pmed.1001012 pubmed: 21445325 pmcid: 3062527
Sterne JA, Rodrigues LC, Guedes IN (1998) Does the efficacy of BCG decline with time since vaccination? Int J Tuberc Lung Dis 2(3):200–207
pubmed: 9526191
Delogu G, Manganelli R, Brennan MJ (2014) Critical research concepts in tuberculosis vaccine development. Clin Microbiol Infect 20(Suppl 5):59–65. https://doi.org/10.1111/1469-0691.12460
doi: 10.1111/1469-0691.12460 pubmed: 24283256
Cadena AM, Flynn JL, Fortune SM (2016) The importance of first impressions: early events in Mycobacterium tuberculosis infection influence outcome. MBio 7(2):e00342–e00316. https://doi.org/10.1128/mBio.00342-16
doi: 10.1128/mBio.00342-16 pubmed: 27048801 pmcid: 4817258
Achkar JM, Jenny-Avital ER (2011) Incipient and subclinical tuberculosis: defining early disease states in the context of host immune response. J Infect Dis 204(Suppl 4):S1179–S1186. https://doi.org/10.1093/infdis/jir451
doi: 10.1093/infdis/jir451 pubmed: 21996700 pmcid: 3192549
Drain PK, Bajema KL, Dowdy D, Dheda K, Naidoo K, Schumacher SG et al (2018) Incipient and subclinical tuberculosis: a clinical review of early stages and progression of infection. Clin Microbiol Rev 31(4):e00021. https://doi.org/10.1128/CMR.00021-18
doi: 10.1128/CMR.00021-18 pubmed: 30021818 pmcid: 6148193
Luca S, Mihaescu T (2013) History of BCG vaccine. Maedica (Buchar) 8(1):53–58
Corbel MJ, Fruth U, Griffiths E, Knezevic I (2004) Report on a WHO consultation on the characterisation of BCG strains, Imperial college, London 15–16 December 2003. Vaccine 22(21–22):2675–2680. https://doi.org/10.1016/j.vaccine.2004.01.050
doi: 10.1016/j.vaccine.2004.01.050 pubmed: 15309814
Andersen P, Doherty TM (2005) The success and failure of BCG—implications for a novel tuberculosis vaccine. Nat Rev Microbiol 3(8):656–662. https://doi.org/10.1038/nrmicro1211
doi: 10.1038/nrmicro1211 pubmed: 16012514
Gasper MA, Hesseling AC, Mohar I, Myer L, Azenkot T, Passmore JS et al (2017) BCG vaccination induces HIV target cell activation in HIV-exposed infants in a randomized trial. JCI Insight 2(7):e91963. https://doi.org/10.1172/jci.insight.91963
doi: 10.1172/jci.insight.91963 pubmed: 28405623 pmcid: 5374072
Tchakoute CT, Hesseling AC, Kidzeru EB, Gamieldien H, Passmore JA, Jones CE et al (2015) Delaying BCG vaccination until 8 weeks of age results in robust BCG-specific T-cell responses in HIV-exposed infants. J Infect Dis 211(3):338–346. https://doi.org/10.1093/infdis/jiu434
doi: 10.1093/infdis/jiu434 pubmed: 25108027
Li J, Zhao A, Tang J, Wang G, Shi Y, Zhan L et al (2020) Tuberculosis vaccine development: from classic to clinical candidates. Eur J Clin Microbiol Infect Dis 39(8):1405–1425. https://doi.org/10.1007/s10096-020-03843-6
doi: 10.1007/s10096-020-03843-6 pubmed: 32060754 pmcid: 7223099
Orme IM (2010) The Achilles heel of BCG. Tuberculosis (Edinb) 90(6):329–332. https://doi.org/10.1016/j.tube.2010.06.002
doi: 10.1016/j.tube.2010.06.002
Nieuwenhuizen NE, Kaufmann SHE (2018) Next-generation vaccines based on Bacille Calmette-Guerin. Front Immunol 9:121. https://doi.org/10.3389/fimmu.2018.00121
doi: 10.3389/fimmu.2018.00121 pubmed: 29459859 pmcid: 5807593
WHO (2018) WHO preferred product characteristics (PPCs). https://www.who.int/immunization/research/ppc-tpp/preferred_product_characteristics/en/
McShane H, Williams A (2014) A review of preclinical animal models utilised for TB vaccine evaluation in the context of recent human efficacy data. Tuberculosis (Edinb) 94(2):105–110. https://doi.org/10.1016/j.tube.2013.11.003
doi: 10.1016/j.tube.2013.11.003
Kaufmann SHE (2020) Vaccination against tuberculosis: revamping BCG by molecular genetics guided by immunology. Front Immunol 11:316. https://doi.org/10.3389/fimmu.2020.00316
doi: 10.3389/fimmu.2020.00316 pubmed: 32174919 pmcid: 7056705
Hatherill M, Tait D, McShane H (2016) Clinical testing of tuberculosis vaccine candidates. Microbiol Spectr 4(5):1–18. https://doi.org/10.1128/microbiolspec.TBTB2-0015-2016
doi: 10.1128/microbiolspec.TBTB2-0015-2016
Sable SB, Posey JE, Scriba TJ (2019) Tuberculosis vaccine development: progress in clinical evaluation. Clin Microbiol Rev 33(1):e00100. https://doi.org/10.1128/CMR.00100-19
doi: 10.1128/CMR.00100-19 pubmed: 31666281 pmcid: 6822991
Evans TG, Schrager L, Thole J (2016) Status of vaccine research and development of vaccines for tuberculosis. Vaccine 34(26):2911–2914. https://doi.org/10.1016/j.vaccine.2016.02.079
doi: 10.1016/j.vaccine.2016.02.079 pubmed: 26973073
Rosser A, Marx FM, Pareek M (2018) Recurrent tuberculosis in the pre-elimination era. Int J Tuberc Lung Dis 22(2):139–150. https://doi.org/10.5588/ijtld.17.0590
doi: 10.5588/ijtld.17.0590 pubmed: 29506610
Hatherill M, White RG, Hawn TR (2019) Clinical development of new TB vaccines: recent advances and next steps. Front Microbiol 10:3154. https://doi.org/10.3389/fmicb.2019.03154
doi: 10.3389/fmicb.2019.03154 pubmed: 32082273
Nunn AJ, Phillips PP, Mitchison DA (2010) Timing of relapse in short-course chemotherapy trials for tuberculosis. Int J Tuberc Lung Dis 14(2):241–242
pubmed: 20074418
Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A et al (2005) Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin. J Clin Invest 115(9):2472–2479. https://doi.org/10.1172/JCI24617
doi: 10.1172/JCI24617 pubmed: 16110326 pmcid: 1187936
Hess J, Miko D, Catic A, Lehmensiek V, Russell DG, Kaufmann SH (1998) Mycobacterium bovis Bacille Calmette-Guerin strains secreting listeriolysin of Listeria monocytogenes. Proc Natl Acad Sci U S A 95(9):5299–5304. https://doi.org/10.1073/pnas.95.9.5299
doi: 10.1073/pnas.95.9.5299 pubmed: 9560270 pmcid: 20255
Kaufmann SH, Cotton MF, Eisele B, Gengenbacher M, Grode L, Hesseling AC et al (2014) The BCG replacement vaccine VPM1002: from drawing board to clinical trial. Expert Rev Vaccines 13(5):619–630. https://doi.org/10.1586/14760584.2014.905746
doi: 10.1586/14760584.2014.905746 pubmed: 24702486
Velmurugan K, Grode L, Chang R, Fitzpatrick M, Laddy D, Hokey D et al (2013) Nonclinical development of BCG replacement vaccine candidates. Vaccines (Basel) 1(2):120–138. https://doi.org/10.3390/vaccines1020120
doi: 10.3390/vaccines1020120
Loxton AG, Knaul JK, Grode L, Gutschmidt A, Meller C, Eisele B et al (2017) Safety and immunogenicity of the recombinant Mycobacterium bovis BCG vaccine VPM1002 in HIV-unexposed newborn infants in South Africa. Clin Vaccine Immunol 24(2):e00439. https://doi.org/10.1128/CVI.00439-16
doi: 10.1128/CVI.00439-16 pubmed: 27974398 pmcid: 5299117
Nieuwenhuizen NE, Kulkarni PS, Shaligram U, Cotton MF, Rentsch CA, Eisele B et al (2017) The recombinant Bacille Calmette-Guerin vaccine VPM1002: ready for clinical efficacy testing. Front Immunol 8:1147. https://doi.org/10.3389/fimmu.2017.01147
doi: 10.3389/fimmu.2017.01147 pubmed: 28974949 pmcid: 5610719
Brazier B, McShane H (2020) Towards new TB vaccines. Semin Immunopathol 42(3):315–331. https://doi.org/10.1007/s00281-020-00794-0
doi: 10.1007/s00281-020-00794-0 pubmed: 32189035 pmcid: 7223498
Andersen P, Scriba TJ (2019) Moving tuberculosis vaccines from theory to practice. Nat Rev Immunol 19(9):550–562. https://doi.org/10.1038/s41577-019-0174-z
doi: 10.1038/s41577-019-0174-z pubmed: 31114037
Arbues A, Aguilo JI, Gonzalo-Asensio J, Marinova D, Uranga S, Puentes E et al (2013) Construction, characterization and preclinical evaluation of MTBVAC, the first live-attenuated M. tuberculosis-based vaccine to enter clinical trials. Vaccine 31(42):4867–4873. https://doi.org/10.1016/j.vaccine.2013.07.051
doi: 10.1016/j.vaccine.2013.07.051 pubmed: 23965219
Spertini F, Audran R, Chakour R, Karoui O, Steiner-Monard V, Thierry AC et al (2015) Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial. Lancet Respir Med 3(12):953–962. https://doi.org/10.1016/S2213-2600(15)00435-X
doi: 10.1016/S2213-2600(15)00435-X pubmed: 26598141
Clark S, Lanni F, Marinova D, Rayner E, Martin C, Williams A (2017) Revaccination of Guinea pigs with the live attenuated Mycobacterium tuberculosis vaccine MTBVAC improves BCG's protection against tuberculosis. J Infect Dis 216(5):525–533. https://doi.org/10.1093/infdis/jix030
doi: 10.1093/infdis/jix030 pubmed: 28329234
Tameris M, Mearns H, Penn-Nicholson A, Gregg Y, Bilek N, Mabwe S et al (2019) Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial. Lancet Respir Med 7(9):757–770. https://doi.org/10.1016/S2213-2600(19)30251-6
doi: 10.1016/S2213-2600(19)30251-6 pubmed: 31416768
Sun R, Skeiky YA, Izzo A, Dheenadhayalan V, Imam Z, Penn E et al (2009) Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; preclinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. Vaccine 27(33):4412–4423. https://doi.org/10.1016/j.vaccine.2009.05.048
doi: 10.1016/j.vaccine.2009.05.048 pubmed: 19500523
Hoft DF, Blazevic A, Selimovic A, Turan A, Tennant J, Abate G et al (2016) Safety and immunogenicity of the recombinant BCG vaccine AERAS-422 in healthy BCG-naive adults: a randomized, active-controlled, first-in-human phase 1 trial. EBioMedicine 7:278–286. https://doi.org/10.1016/j.ebiom.2016.04.010
doi: 10.1016/j.ebiom.2016.04.010 pubmed: 27322481 pmcid: 4909487
Cardona PJ (2006) RUTI: a new chance to shorten the treatment of latent tuberculosis infection. Tuberculosis (Edinb) 86(3–4):273–289. https://doi.org/10.1016/j.tube.2006.01.024
doi: 10.1016/j.tube.2006.01.024
Guirado E, Gil O, Caceres N, Singh M, Vilaplana C, Cardona PJ (2008) Induction of a specific strong polyantigenic cellular immune response after short-term chemotherapy controls bacillary reactivation in murine and Guinea pig experimental models of tuberculosis. Clin Vaccine Immunol 15(8):1229–1237. https://doi.org/10.1128/CVI.00094-08
doi: 10.1128/CVI.00094-08 pubmed: 18524883 pmcid: 2519306
Vilaplana C, Gil O, Caceres N, Pinto S, Diaz J, Cardona PJ (2011) Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis. PLoS One 6(5):e20404. https://doi.org/10.1371/journal.pone.0020404
doi: 10.1371/journal.pone.0020404 pubmed: 21647222 pmcid: 3101251
Vilaplana C, Montane E, Pinto S, Barriocanal AM, Domenech G, Torres F et al (2010) Double-blind, randomized, placebo-controlled phase I clinical trial of the therapeutical antituberculous vaccine RUTI. Vaccine 28(4):1106–1116. https://doi.org/10.1016/j.vaccine.2009.09.134
doi: 10.1016/j.vaccine.2009.09.134 pubmed: 19853680
Nell AS, D'Lom E, Bouic P, Sabate M, Bosser R, Picas J et al (2014) Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection. PLoS One 9(2):e89612. https://doi.org/10.1371/journal.pone.0089612
doi: 10.1371/journal.pone.0089612 pubmed: 24586912 pmcid: 3935928
von Reyn CF, Lahey T, Arbeit RD, Landry B, Kailani L, Adams LV et al (2017) Safety and immunogenicity of an inactivated whole cell tuberculosis vaccine booster in adults primed with BCG: a randomized, controlled trial of DAR-901. PLoS One 12(5):e0175215. https://doi.org/10.1371/journal.pone.0175215
doi: 10.1371/journal.pone.0175215
Lahey T, Arbeit RD, Bakari M, Horsburgh CR, Matee M, Waddell R et al (2010) Immunogenicity of a protective whole cell mycobacterial vaccine in HIV-infected adults: a phase III study in Tanzania. Vaccine 28(48):7652–7658. https://doi.org/10.1016/j.vaccine.2010.09.041
doi: 10.1016/j.vaccine.2010.09.041 pubmed: 20875492 pmcid: 2981786
von Reyn CF, Mtei L, Arbeit RD, Waddell R, Cole B, Mackenzie T et al (2010) Prevention of tuberculosis in Bacille Calmette-Guerin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS 24(5):675–685. https://doi.org/10.1097/QAD.0b013e3283350f1b
doi: 10.1097/QAD.0b013e3283350f1b
Lahey T, Laddy D, Hill K, Schaeffer J, Hogg A, Keeble J et al (2016) Immunogenicity and protective efficacy of the DAR-901 booster vaccine in a murine model of tuberculosis. PLoS One 11(12):e0168521. https://doi.org/10.1371/journal.pone.0168521
doi: 10.1371/journal.pone.0168521 pubmed: 27997597 pmcid: 5173179
Yang XY, Chen QF, Li YP, Wu SM (2011) Mycobacterium vaccae as adjuvant therapy to anti-tuberculosis chemotherapy in never-treated tuberculosis patients: a meta-analysis. PLoS One 6(9):e23826. https://doi.org/10.1371/journal.pone.0023826
doi: 10.1371/journal.pone.0023826 pubmed: 21909406 pmcid: 3167806
Hernandez-Pando R, Pavon L, Arriaga K, Orozco H, Madrid-Marina V, Rook G (1997) Pathogenesis of tuberculosis in mice exposed to low and high doses of an environmental mycobacterial saprophyte before infection. Infect Immun 65(8):3317–3327
doi: 10.1128/iai.65.8.3317-3327.1997
Waddell RD, Chintu C, Lein AD, Zumla A, Karagas MR, Baboo KS et al (2000) Safety and immunogenicity of a five-dose series of inactivated mycobacterium vaccae vaccination for the prevention of HIV-associated tuberculosis. Clin Infect Dis 30(Suppl 3):S309–S315. https://doi.org/10.1086/313880
doi: 10.1086/313880 pubmed: 10875806
Vuola JM, Ristola MA, Cole B, Jarviluoma A, Tvaroha S, Ronkko T et al (2003) Immunogenicity of an inactivated mycobacterial vaccine for the prevention of HIV-associated tuberculosis: a randomized, controlled trial. AIDS 17(16):2351–2355. https://doi.org/10.1097/00002030-200311070-00010
doi: 10.1097/00002030-200311070-00010 pubmed: 14571187
Talwar GP, Gupta JC, Mustafa AS, Kar HK, Katoch K, Parida SK et al (2017) Development of a potent invigorator of immune responses endowed with both preventive and therapeutic properties. Biol Theory 11:55–63. https://doi.org/10.2147/BTT.S128308
doi: 10.2147/BTT.S128308
Saqib M, Khatri R, Singh B, Gupta A, Kumar A, Bhaskar S (2016) Mycobacterium indicus pranii as a booster vaccine enhances BCG induced immunity and confers higher protection in animal models of tuberculosis. Tuberculosis (Edinb) 101:164–173. https://doi.org/10.1016/j.tube.2016.10.002
doi: 10.1016/j.tube.2016.10.002
Sharma SK, Katoch K, Sarin R, Balambal R, Kumar Jain N, Patel N et al (2017) Efficacy and safety of Mycobacterium indicus pranii as an adjunct therapy in category II pulmonary tuberculosis in a randomized trial. Sci Rep 7(1):3354. https://doi.org/10.1038/s41598-017-03514-1
doi: 10.1038/s41598-017-03514-1 pubmed: 28611374 pmcid: 5469738
Stewart E, Triccas JA, Petrovsky N (2019) Adjuvant strategies for more effective tuberculosis vaccine immunity. Microorganisms 7(8):255. https://doi.org/10.3390/microorganisms7080255
doi: 10.3390/microorganisms7080255 pmcid: 6724148
Usman MM, Ismail S, Teoh TC (2017) Vaccine research and development: tuberculosis as a global health threat. Cent Eur J Immunol 42(2):196–204. https://doi.org/10.5114/ceji.2017.69362
doi: 10.5114/ceji.2017.69362 pubmed: 28867962 pmcid: 5573893
Agger EM, Rosenkrands I, Olsen AW, Hatch G, Williams A, Kritsch C et al (2006) Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine 24(26):5452–5460. https://doi.org/10.1016/j.vaccine.2006.03.072
doi: 10.1016/j.vaccine.2006.03.072 pubmed: 16675077
Kamath AT, Rochat AF, Valenti MP, Agger EM, Lingnau K, Andersen P et al (2008) Adult-like antimycobacterial T cell and in vivo dendritic cell responses following neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant. PLoS One 3(11):e3683. https://doi.org/10.1371/journal.pone.0003683
doi: 10.1371/journal.pone.0003683 pubmed: 18997860 pmcid: 2577009
van Dissel JT, Arend SM, Prins C, Bang P, Tingskov PN, Lingnau K et al (2010) Ag85B-ESAT-6 adjuvanted with IC31 promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in naive human volunteers. Vaccine 28(20):3571–3581. https://doi.org/10.1016/j.vaccine.2010.02.094
doi: 10.1016/j.vaccine.2010.02.094 pubmed: 20226890
van Dissel JT, Soonawala D, Joosten SA, Prins C, Arend SM, Bang P et al (2011) Ag85B-ESAT-6 adjuvanted with IC31(R) promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in volunteers with previous BCG vaccination or tuberculosis infection. Vaccine 29(11):2100–2109. https://doi.org/10.1016/j.vaccine.2010.12.135
doi: 10.1016/j.vaccine.2010.12.135 pubmed: 21256189
Hussein J, Zewdie M, Yamuah L, Bedru A, Abebe M, Dagnew AF et al (2018) A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31(R) in people living in a TB-endemic area. Trials 19(1):24. https://doi.org/10.1186/s13063-017-2354-0
doi: 10.1186/s13063-017-2354-0 pubmed: 29321075 pmcid: 5764015
Reither K, Katsoulis L, Beattie T, Gardiner N, Lenz N, Said K et al (2014) Safety and immunogenicity of H1/IC31(R), an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-Centre, double-blind, randomized, placebo-controlled trial. PLoS One 9(12):e114602. https://doi.org/10.1371/journal.pone.0114602
doi: 10.1371/journal.pone.0114602 pubmed: 25490675 pmcid: 4260867
Aagaard C, Hoang T, Dietrich J, Cardona PJ, Izzo A, Dolganov G et al (2011) A multistage tuberculosis vaccine that confers efficient protection before and after exposure. Nat Med 17(2):189–194. https://doi.org/10.1038/nm.2285
doi: 10.1038/nm.2285 pubmed: 21258338
Lin PL, Dietrich J, Tan E, Abalos RM, Burgos J, Bigbee C et al (2012) The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection. J Clin Invest 122(1):303–314. https://doi.org/10.1172/JCI46252
doi: 10.1172/JCI46252 pubmed: 22133873
Luabeya AK, Kagina BM, Tameris MD, Geldenhuys H, Hoff ST, Shi Z et al (2015) First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine 33(33):4130–4140. https://doi.org/10.1016/j.vaccine.2015.06.051
doi: 10.1016/j.vaccine.2015.06.051 pubmed: 26095509
Suliman S, Luabeya AKK, Geldenhuys H, Tameris M, Hoff ST, Shi Z et al (2019) Dose optimization of H56:IC31 vaccine for tuberculosis-endemic populations. A double-blind, placebo-controlled, dose-selection trial. Am J Respir Crit Care Med 199(2):220–231. https://doi.org/10.1164/rccm.201802-0366OC
doi: 10.1164/rccm.201802-0366OC pubmed: 30092143
Aagaard C, Hoang TT, Izzo A, Billeskov R, Troudt J, Arnett K et al (2009) Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose. PLoS One 4(6):e5930. https://doi.org/10.1371/journal.pone.0005930
doi: 10.1371/journal.pone.0005930 pubmed: 19529771 pmcid: 2691953
Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S et al (2017) Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: two phase I dose escalation trials. Vaccine 35(12):1652–1661. https://doi.org/10.1016/j.vaccine.2017.01.055
doi: 10.1016/j.vaccine.2017.01.055 pubmed: 28216183
Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N et al (2018) Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N Engl J Med 379(2):138–149. https://doi.org/10.1056/NEJMoa1714021
doi: 10.1056/NEJMoa1714021 pubmed: 29996082 pmcid: 5937161
Baldwin SL, Bertholet S, Reese VA, Ching LK, Reed SG, Coler RN (2012) The importance of adjuvant formulation in the development of a tuberculosis vaccine. J Immunol 188(5):2189–2197. https://doi.org/10.4049/jimmunol.1102696
doi: 10.4049/jimmunol.1102696 pubmed: 22291184
Bertholet S, Ireton GC, Ordway DJ, Windish HP, Pine SO, Kahn M et al (2010) A defined tuberculosis vaccine candidate boosts BCG and protects against multidrug-resistant Mycobacterium tuberculosis. Sci Transl Med 2(53):53ra74. https://doi.org/10.1126/scitranslmed.3001094
doi: 10.1126/scitranslmed.3001094 pubmed: 20944089 pmcid: 3110937
Coler RN, Bertholet S, Pine SO, Orr MT, Reese V, Windish HP et al (2013) Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment. J Infect Dis 207(8):1242–1252. https://doi.org/10.1093/infdis/jis425
doi: 10.1093/infdis/jis425 pubmed: 22891286
Coler RN, Day TA, Ellis R, Piazza FM, Beckmann AM, Vergara J et al (2018) 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 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 (2018) 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 6(4):287–298. https://doi.org/10.1016/S2213-2600(18)30077-8
doi: 10.1016/S2213-2600(18)30077-8 pubmed: 29595510
Schrager LK, Vekemens J, Drager N, Lewinsohn DM, Olesen OF (2020) The status of tuberculosis vaccine development. Lancet Infect Dis 20(3):e28–e37. https://doi.org/10.1016/S1473-3099(19)30625-5
doi: 10.1016/S1473-3099(19)30625-5 pubmed: 32014117
Skeiky YA, Alderson MR, Ovendale PJ, Guderian JA, Brandt L, Dillon DC et al (2004) Differential immune responses and protective efficacy induced by components of a tuberculosis polyprotein vaccine, Mtb72F, delivered as naked DNA or recombinant protein. J Immunol 172(12):7618–7628. https://doi.org/10.4049/jimmunol.172.12.7618
doi: 10.4049/jimmunol.172.12.7618 pubmed: 15187142
Brandt L, Skeiky YA, Alderson MR, Lobet Y, Dalemans W, Turner OC et al (2004) The protective effect of the Mycobacterium bovis BCG vaccine is increased by coadministration with the Mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected Guinea pigs. Infect Immun 72(11):6622–6632. https://doi.org/10.1128/IAI.72.11.6622-6632.2004
doi: 10.1128/IAI.72.11.6622-6632.2004 pubmed: 15501795 pmcid: 523007
Reed SG, Coler RN, Dalemans W, Tan EV, DeLa Cruz EC, Basaraba RJ et al (2009) Defined tuberculosis vaccine, Mtb72F/AS02A, evidence of protection in cynomolgus monkeys. Proc Natl Acad Sci U S A 106(7):2301–2306. https://doi.org/10.1073/pnas.0712077106
doi: 10.1073/pnas.0712077106 pubmed: 19188599 pmcid: 2650151
Ji Z, Jian M, Chen T, Luo L, Li L, Dai X et al (2019) Immunogenicity and safety of the M72/AS01E candidate vaccine against tuberculosis: a meta-analysis. Front Immunol 10:2089. https://doi.org/10.3389/fimmu.2019.02089
doi: 10.3389/fimmu.2019.02089 pubmed: 31552037 pmcid: 6735267
Montoya J, Solon JA, Cunanan SR, Acosta L, Bollaerts A, Moris P et al (2013) A randomized, controlled dose-finding phase II study of the M72/AS01 candidate tuberculosis vaccine in healthy PPD-positive adults. J Clin Immunol 33(8):1360–1375. https://doi.org/10.1007/s10875-013-9949-3
doi: 10.1007/s10875-013-9949-3 pubmed: 24142232 pmcid: 3825318
Gillard P, Yang PC, Danilovits M, Su WJ, Cheng SL, Pehme L et al (2016) Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: a phase II randomised study. Tuberculosis (Edinb) 100:118–127. https://doi.org/10.1016/j.tube.2016.07.005
doi: 10.1016/j.tube.2016.07.005
Penn-Nicholson A, Geldenhuys H, Burny W, van der Most R, Day CL, Jongert E et al (2015) Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting. Vaccine 33(32):4025–4034. https://doi.org/10.1016/j.vaccine.2015.05.088
doi: 10.1016/j.vaccine.2015.05.088 pubmed: 26072017 pmcid: 5845829
Van Der Meeren O, Hatherill M, Nduba V, Wilkinson RJ, Muyoyeta M, Van Brakel E et al (2018) Phase 2b controlled trial of M72/AS01E vaccine to prevent tuberculosis. N Engl J Med 379(17):1621–1634. https://doi.org/10.1056/NEJMoa1803484
doi: 10.1056/NEJMoa1803484
Kumarasamy N, Poongulali S, Beulah FE, Akite EJ, Ayuk LN, Bollaerts A et al (2018) Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: results from a phase II randomized controlled trial. Medicine (Baltimore) 97(45):e13120. https://doi.org/10.1097/MD.0000000000013120
doi: 10.1097/MD.0000000000013120
Tkachuk AP, Gushchin VA, Potapov VD, Demidenko AV, Lunin VG, Gintsburg AL (2017) Multi-subunit BCG booster vaccine GamTBvac: assessment of immunogenicity and protective efficacy in murine and Guinea pig TB models. PLoS One 12(4):e0176784. https://doi.org/10.1371/journal.pone.0176784
doi: 10.1371/journal.pone.0176784 pubmed: 28453555 pmcid: 5409163
Vasina DV, Kleymenov DA, Manuylov VA, Mazunina EP, Koptev EY, Tukhovskaya EA et al (2019) First-in-human trials of GamTBvac, a recombinant subunit tuberculosis vaccine candidate: safety and immunogenicity assessment. Vaccines (Basel) 7(4):166. https://doi.org/10.3390/vaccines7040166
doi: 10.3390/vaccines7040166
Rowland R, McShane H (2011) Tuberculosis vaccines in clinical trials. Expert Rev Vaccines 10(5):645–658. https://doi.org/10.1586/erv.11.28
doi: 10.1586/erv.11.28 pubmed: 21604985 pmcid: 3409871
Pang Y, Zhao A, Cohen C, Kang W, Lu J, Wang G et al (2016) Current status of new tuberculosis vaccine in children. Hum Vaccin Immunother 12(4):960–970. https://doi.org/10.1080/21645515.2015.1120393
doi: 10.1080/21645515.2015.1120393 pubmed: 27002369 pmcid: 4962963
Goonetilleke NP, McShane H, Hannan CM, Anderson RJ, Brookes RH, Hill AV (2003) Enhanced immunogenicity and protective efficacy against Mycobacterium tuberculosis of bacille Calmette-Guerin vaccine using mucosal administration and boosting with a recombinant modified vaccinia virus Ankara. J Immunol 171(3):1602–1609. https://doi.org/10.4049/jimmunol.171.3.1602
doi: 10.4049/jimmunol.171.3.1602 pubmed: 12874255
Verreck FA, Vervenne RA, Kondova I, van Kralingen KW, Remarque EJ, Braskamp G et al (2009) MVA.85A boosting of BCG and an attenuated, phoP deficient M. tuberculosis vaccine both show protective efficacy against tuberculosis in rhesus macaques. PLoS One 4(4):e5264. https://doi.org/10.1371/journal.pone.0005264
doi: 10.1371/journal.pone.0005264 pubmed: 19367339 pmcid: 2666807
Williams A, Goonetilleke NP, McShane H, Clark SO, Hatch G, Gilbert SC et al (2005) Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in Guinea pigs. Infect Immun 73(6):3814–3816. https://doi.org/10.1128/IAI.73.6.3814-3816.2005
doi: 10.1128/IAI.73.6.3814-3816.2005 pubmed: 15908420 pmcid: 1111825
Williams A, Hatch GJ, Clark SO, Gooch KE, Hatch KA, Hall GA et al (2005) Evaluation of vaccines in the EU TB vaccine cluster using a Guinea pig aerosol infection model of tuberculosis. Tuberculosis (Edinb) 85(1–2):29–38. https://doi.org/10.1016/j.tube.2004.09.009
doi: 10.1016/j.tube.2004.09.009
McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K et al (2004) Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med 10(11):1240–1244. https://doi.org/10.1038/nm1128
doi: 10.1038/nm1128 pubmed: 15502839
Hawkridge T, Scriba TJ, Gelderbloem S, Smit E, Tameris M, Moyo S et al (2008) Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis 198(4):544–552. https://doi.org/10.1086/590185
doi: 10.1086/590185 pubmed: 18582195
Sander CR, Pathan AA, Beveridge NE, Poulton I, Minassian A, Alder N et al (2009) Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in Mycobacterium tuberculosis-infected individuals. Am J Respir Crit Care Med 179(8):724–733. https://doi.org/10.1164/rccm.200809-1486OC
doi: 10.1164/rccm.200809-1486OC pubmed: 19151191 pmcid: 2858810
Minassian AM, Rowland R, Beveridge NE, Poulton ID, Satti I, Harris S et al (2011) A phase I study evaluating the safety and immunogenicity of MVA85A, a candidate TB vaccine, in HIV-infected adults. BMJ Open 1(2):e000223. https://doi.org/10.1136/bmjopen-2011-000223
doi: 10.1136/bmjopen-2011-000223 pubmed: 22102640 pmcid: 3221299
Nicol MP, Grobler LA (2010) MVA-85A, a novel candidate booster vaccine for the prevention of tuberculosis in children and adults. Curr Opin Mol Ther 12(1):124–134
pubmed: 20140824
Pathan AA, Minassian AM, Sander CR, Rowland R, Porter DW, Poulton ID et al (2012) Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults. Vaccine 30(38):5616–5624. https://doi.org/10.1016/j.vaccine.2012.06.084
doi: 10.1016/j.vaccine.2012.06.084 pubmed: 22789508 pmcid: 3424417
Scriba TJ, Tameris M, Mansoor N, Smit E, van der Merwe L, Mauff K et al (2011) Dose-finding study of the novel tuberculosis vaccine, MVA85A, in healthy BCG-vaccinated infants. J Infect Dis 203(12):1832–1843. https://doi.org/10.1093/infdis/jir195
doi: 10.1093/infdis/jir195 pubmed: 21606542
Meyer J, Harris SA, Satti I, Poulton ID, Poyntz HC, Tanner R et al (2013) Comparing the safety and immunogenicity of a candidate TB vaccine MVA85A administered by intramuscular and intradermal delivery. Vaccine 31(7):1026–1033. https://doi.org/10.1016/j.vaccine.2012.12.042
doi: 10.1016/j.vaccine.2012.12.042 pubmed: 23266342 pmcid: 5405058
Satti I, Meyer J, Harris SA, Manjaly Thomas ZR, Griffiths K, Antrobus RD et al (2014) Safety and immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in BCG-vaccinated healthy adults: a phase 1, double-blind, randomised controlled trial. Lancet Infect Dis 14(10):939–946. https://doi.org/10.1016/S1473-3099(14)70845-X
doi: 10.1016/S1473-3099(14)70845-X pubmed: 25151225 pmcid: 4178237
Scriba TJ, Tameris M, Smit E, van der Merwe L, Hughes EJ, Kadira B et al (2012) A phase IIa trial of the new tuberculosis vaccine, MVA85A, in HIV- and/or Mycobacterium tuberculosis-infected adults. Am J Respir Crit Care Med 185(7):769–778. https://doi.org/10.1164/rccm.201108-1548OC
doi: 10.1164/rccm.201108-1548OC pubmed: 22281831 pmcid: 3326425
Vilaplana C, Cardona PJ (2019) How far are we away from an improved vaccine for tuberculosis? Current efforts and future prospects. Arch Bronconeumol 55(7):373–377. https://doi.org/10.1016/j.arbres.2018.11.002
doi: 10.1016/j.arbres.2018.11.002 pubmed: 30594319
Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC et al (2012) A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS One 7(7):e40385. https://doi.org/10.1371/journal.pone.0040385
doi: 10.1371/journal.pone.0040385 pubmed: 22808149 pmcid: 3396660
Stylianou E, Griffiths KL, Poyntz HC, Harrington-Kandt R, Dicks MD, Stockdale L et al (2015) Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A. Vaccine 33(48):6800–6808. https://doi.org/10.1016/j.vaccine.2015.10.017
doi: 10.1016/j.vaccine.2015.10.017 pubmed: 26478198 pmcid: 4678294
Wilkie M, Satti I, Minhinnick A, Harris S, Riste M, Ramon RL et al (2020) A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime—MVA85A boost in healthy UK adults. Vaccine 38(4):779–789. https://doi.org/10.1016/j.vaccine.2019.10.102
doi: 10.1016/j.vaccine.2019.10.102 pubmed: 31735500 pmcid: 6985898
Wang J, Thorson L, Stokes RW, Santosuosso M, Huygen K, Zganiacz A et al (2004) Single mucosal, but not parenteral, immunization with recombinant adenoviral-based vaccine provides potent protection from pulmonary tuberculosis. J Immunol 173(10):6357–6365. https://doi.org/10.4049/jimmunol.173.10.6357
doi: 10.4049/jimmunol.173.10.6357 pubmed: 15528375
Santosuosso M, McCormick S, Zhang X, Zganiacz A, Xing Z (2006) Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis. Infect Immun 74(8):4634–4643. https://doi.org/10.1128/IAI.00517-06
doi: 10.1128/IAI.00517-06 pubmed: 16861651 pmcid: 1539608
Santosuosso M, Zhang X, McCormick S, Wang J, Hitt M, Xing Z (2005) Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based mucosal immunization preferentially elicits sustained accumulation of immune protective CD4 and CD8 T cells within the airway lumen. J Immunol 174(12):7986–7994. https://doi.org/10.4049/jimmunol.174.12.7986
doi: 10.4049/jimmunol.174.12.7986 pubmed: 15944305
Smaill F, Jeyanathan M, Smieja M, Medina MF, Thanthrige-Don N, Zganiacz A et al (2013) A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell responses in humans despite preexisting anti-adenovirus immunity. Sci Transl Med 5(205):205ra134. https://doi.org/10.1126/scitranslmed.3006843
doi: 10.1126/scitranslmed.3006843 pubmed: 24089406
Havenga M, Vogels R, Zuijdgeest D, Radosevic K, Mueller S, Sieuwerts M et al (2006) Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells. J Gen Virol 87(Pt 8):2135–2143. https://doi.org/10.1099/vir.0.81956-0
doi: 10.1099/vir.0.81956-0 pubmed: 16847108
Radosevic K, Wieland CW, Rodriguez A, Weverling GJ, Mintardjo R, Gillissen G et al (2007) Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infect Immun 75(8):4105–4115. https://doi.org/10.1128/IAI.00004-07
doi: 10.1128/IAI.00004-07 pubmed: 17526747 pmcid: 1951991
Darrah PA, Bolton DL, Lackner AA, Kaushal D, Aye PP, Mehra S et al (2014) Aerosol vaccination with AERAS-402 elicits robust cellular immune responses in the lungs of rhesus macaques but fails to protect against high-dose Mycobacterium tuberculosis challenge. J Immunol 193(4):1799–1811. https://doi.org/10.4049/jimmunol.1400676
doi: 10.4049/jimmunol.1400676 pubmed: 25024382
Churchyard GJ, Snowden MA, Hokey D, Dheenadhayalan V, McClain JB, Douoguih M et al (2015) The safety and immunogenicity of an adenovirus type 35-vectored TB vaccine in HIV-infected, BCG-vaccinated adults with CD4(+) T cell counts >350 cells/mm(3). Vaccine 33(15):1890–1896. https://doi.org/10.1016/j.vaccine.2015.02.004
doi: 10.1016/j.vaccine.2015.02.004 pubmed: 25698492
Hoft DF, Blazevic A, Stanley J, Landry B, Sizemore D, Kpamegan E et al (2012) A recombinant adenovirus expressing immunodominant TB antigens can significantly enhance BCG-induced human immunity. Vaccine 30(12):2098–2108. https://doi.org/10.1016/j.vaccine.2012.01.048
doi: 10.1016/j.vaccine.2012.01.048 pubmed: 22296955
Kagina BM, Tameris MD, Geldenhuys H, Hatherill M, Abel B, Hussey GD et al (2014) The novel tuberculosis vaccine, AERAS-402, is safe in healthy infants previously vaccinated with BCG, and induces dose-dependent CD4 and CD8T cell responses. Vaccine 32(45):5908–5917. https://doi.org/10.1016/j.vaccine.2014.09.001
doi: 10.1016/j.vaccine.2014.09.001 pubmed: 25218194
Tameris M, Hokey DA, Nduba V, Sacarlal J, Laher F, Kiringa G et al (2015) A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants. Vaccine 33(25):2944–2954. https://doi.org/10.1016/j.vaccine.2015.03.070
doi: 10.1016/j.vaccine.2015.03.070 pubmed: 25936724 pmcid: 6698638
Khoshnood S, Heidary M, Haeili M, Drancourt M, Darban-Sarokhalil D, Nasiri MJ et al (2018) Novel vaccine candidates against Mycobacterium tuberculosis. Int J Biol Macromol 120(Pt A):180–188. https://doi.org/10.1016/j.ijbiomac.2018.08.037
doi: 10.1016/j.ijbiomac.2018.08.037 pubmed: 30098365

Auteurs

Radha Gopalaswamy (R)

Department of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chennai, Tamilnadu, India.

Selvakumar Subbian (S)

The Public Health Research Institute Center at New Jersey Medical School, Rutgers University, Newark, NJ, USA. subbiase@njms.rutgers.edu.

Articles similaires

Evaluating the efficacy of telesurgery with dual console SSI Mantra Surgical Robotic System: experiment on animal model and clinical trials.

Sudhir Prem Srivastava, Vishwajyoti Pascual Srivastava, Avinesh Singh et al.
1.00
Robotic Surgical Procedures Animals Humans Telemedicine Models, Animal

Odour generalisation and detection dog training.

Lyn Caldicott, Thomas W Pike, Helen E Zulch et al.
1.00
Animals Odorants Dogs Generalization, Psychological Smell

FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.

Minle Li, Xuan Chen, Pengfei Qu et al.
1.00
Animals TOR Serine-Threonine Kinases Colorectal Neoplasms Colitis Mice

Use of organic material provided by an automatic enrichment device by weaner pigs and its influence on tail lesions.

Philipp Heseker, Jeanette Probst, Stefanie Ammer et al.
1.00
Animals Tail Swine Behavior, Animal Animal Husbandry

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Facteurs biologiques › Antigènes › Antigènes bactériens › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antibactériens › Vaccins antituberculeux › Vaccin BCG › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Maladies du système immunitaire › Déficits immunitaires › Infections à VIH › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Bactéries › Bactéries à Gram positif › Bâtonnets à Gram positif › Bâtonnets asporogènes à Gram positif › Bâtonnets asporogènes réguliers à Gram positif › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Infection › Infections bactériennes et mycoses › Infections bactériennes › Infections bactériennes à Gram positif › Infections à Actinomycetales › Infections à Mycobacterium › Tuberculose › An Update on Tuberculosis Vaccines.
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antibactériens › Vaccins antituberculeux › An Update on Tuberculosis Vaccines.