Advax4 delta inulin combination adjuvant together with ECMX, a fusion construct of four protective mTB antigens, induces a potent Th1 immune response and protects mice against Mycobacterium tuberculosis infection

References

• World Health Organisation. Global tuberculosis report 2016. ISBN 9789241565394. Available at: http://www.who.int/tb/publications/global_report/en/
   Google Scholar
• Manabe YC, Bishai WR. Latent Mycobacterium tuberculosis-persistence, patience, and winning by waiting. Nat Med. 2000;6:1327–9. https://doi.org/10.1038/82139 PMID:11100115
   PubMed Web of Science ®Google Scholar
• Fletcher HA, Schrager L. TB vaccine development and the End TB Strategy: importance and current status. Trans R Soc Trop Med Hyg. 2016;110:212–8. https://doi.org/10.1093/trstmh/trw016 PMID:27076508
   PubMed Web of Science ®Google Scholar
• Dockrell HM. Towards new TB vaccines: What are the challenges?. Pathog Dis. 2016;74:ftw016. https://doi.org/10.1093/femspd/ftw016 PMID:26960944
   PubMed Web of Science ®Google Scholar
• Agger, EM. Novel adjuvant formulations for delivery of anti-tuberculosis vaccine candidates. Adv Drug Deliv Rev. 2016;1:73–82. https://doi.org/10.1016/j.addr.2015.11.012
   Google Scholar
• de Sousa EM, da Costa AC, Trentini MM, de Araújo Filho JA, Kipnis A, Junqueira- Kipnis AP. Immunogenicity of a fusion protein containing immunodominant epitopes of Ag85C, MPT51, and HspX from Mycobacterium tuberculosis in mice and active TB infection. PLoS One. 2012;7:e47781. https://doi.org/10.1371/journal.pone.0047781 PMID:23133523
   PubMed Web of Science ®Google Scholar
• Junqueira-Kipnis AP, de Oliveira FM, Trentini MM, Tiwari S, Chen B, Resende DP, Silva BD, Chen M, Tesfa L, Jacobs WR Jr, et al. Prime-boost with Mycobacterium smegmatis recombinant vaccine improves protection in mice infected with Mycobacterium tuberculosis. PLoS One. 2013;8:e78639. https://doi.org/10.1371/journal.pone.0078639 PMID:24250805
   PubMed Web of Science ®Google Scholar
• da Costa AC, Costa-Júnior Ade O, de Oliveira FM, Nogueira SV, Rosa JD, Resende DP, Kipnis A, Junqueira-Kipnis AP. A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis. PLoS One 2014;9:e112848. https://doi.org/10.1371/journal.pone.0112848 PMID:25398087
   PubMed Web of Science ®Google Scholar
• Chatterjee S, Dwivedi VP, Singh Y, Siddiqui I, Sharma P, Van Kaer L, Chattopadhyay D, Das G. Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner. PLoS Pathog. 2011;7:e1002378. https://doi.org/10.1371/journal.ppat.1002378 PMID:22102818
   PubMed Web of Science ®Google Scholar
• Cooper PD, Petrovsky N. Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 ->1] poly(fructo-furanosyl) α-D-glucose polymers. Glycobiology. 2011;21:595–606. https://doi.org/10.1093/glycob/cwq201 PMID:21147758
   PubMed Web of Science ®Google Scholar
• Wong TM, Petrovsky N, Bissel SJ, Wiley CA, Ross TM. Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology. Hum Vaccin Immunother. 2016;12:2096–2105. https://doi.org/10.1080/21645515.2016.1162931 PMID:27215855
   PubMed Web of Science ®Google Scholar
• Petrovsky N, Larena M, Siddharthan V, Prow NA, Hall RA, Lobigs M, Morrey J. An inactivated cell culture Japanese encephalitis vaccine (JE-ADVAX) formulated with delta inulin adjuvant provides robust heterologous protection against West Nile encephalitis via cross-protective memory B cells and neutralizing antibody. J Virol. 2013;87:10324–33. https://doi.org/10.1128/JVI.00480-13 PMID:23864620
   PubMed Web of Science ®Google Scholar
• Bielefeldt-Ohmann H, Prow NA, Wang W, Tan CS, Coyle M, Douma A, Hobson-Peters J, Kidd L, Hall RA, Petrovsky N. Safety and immunogenicity of a delta inulin adjuvanted inactivated Japanese encephalitis virus vaccine in pregnant mares and foals. Veterinary Research. 2014;45:130. https://doi.org/10.1186/s13567-014-0130-7 PMID:25516480
   PubMed Web of Science ®Google Scholar
• Honda-Okubo Y, Ong CH, Petrovsky N. Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single-dose influenza vaccine protection. Vaccine. 2015;33:4892–900. https://doi.org/10.1016/j.vaccine.2015.07.051 PMID:26232344
   PubMed Web of Science ®Google Scholar
• Li L, Honda-Okubo Y, Li C, Sajkov D, Petrovsky N. Delta inulin adjuvant enhances plasmablast generation, Expression of activation-induced cytidine deaminase and B-Cell affinity maturation in human subjects receiving seasonal influenza vaccine. PLoS One. 2015;10:e0132003. https://doi.org/10.1371/journal.pone.0132003 PMID:26177480
   PubMed Web of Science ®Google Scholar
• Honda-Okubo Y, Kolpe A, Li L, Petrovsky N. A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection. Vaccine. 2014;32:4651–9. https://doi.org/10.1016/j.vaccine.2014.06.057 PMID:24958701
   PubMed Web of Science ®Google Scholar
• McPherson C, Chubet R, Holtz K, Honda-Okubo Y, Barnard D, Cox M, Petrovsky N. Development of a SARS coronavirus vaccine from recombinant spike protein plus delta inulin adjuvant. Methods Mol Biol. 2016;1403:269–84. https://doi.org/10.1007/978-1-4939-3387-7_14 PMID:27076136
   PubMedGoogle Scholar
• Rodriguez-Del Rio E, Marradi M, Calderon-Gonzalez R, Frande-Cabanes E, Penadés S, Petrovsky N, Alvarez-Dominguez C. A gold glyco-nanoparticle carrying a Listeriolysin O peptide and formulated with Advax™ delta inulin adjuvant induces robust T-cell protection against listeria infection. Vaccine. 2015;33:1465–73. https://doi.org/10.1016/j.vaccine.2015.01.062 PMID:25659269
   PubMed Web of Science ®Google Scholar
• Hess JA, Zhan B, Torigian AR, Patton JB, Petrovsky N, Zhan T, Bottazzi ME, Hotez PJ, Klei TR, Lustigman S, et al. The immunomodulatory role of adjuvants in vaccines formulated with the recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in mice. PLoS Negl Trop Dis. 2016;10:e0004797. https://doi.org/10.1371/journal.pntd.0004797 PMID:27387453
   PubMed Web of Science ®Google Scholar
• Feinen B, Petrovsky N, Verma A, Merkel TJ. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant. Clin Vaccine Immunol. 2014;21:580–6. https://doi.org/10.1128/CVI.00019-14 PMID:24554695
   PubMed Web of Science ®Google Scholar
• Gordon D, Kelley P, Heinzel S, Cooper P, Petrovsky N. Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study. Vaccine. 2014;32:6469–77. https://doi.org/10.1016/j.vaccine.2014.09.034 PMID:25267153
   PubMed Web of Science ®Google Scholar
• Gordon DL, Sajkov D, Honda-Okubo Y, Wilks SH, Aban M, Barr IG, Petrovsky N. Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant. Vaccine. 2016;34:3780–6. https://doi.org/10.1016/j.vaccine.2016.05.071 PMID:27342914
   PubMed Web of Science ®Google Scholar
• Heddle R, Russo P, Petrovsky N, Hanna R, Smith A. Immunotherapy – 2076. A controlled study of delta inulin-adjuvanted honey bee venom immunotherapy. World Allergy Organ J. 2013;6:P158.
   Google Scholar
• Petrovsky N. Freeing vaccine adjuvants from dangerous immunological dogma. Expert Rev Vaccines. 2008;7:7–10. https://doi.org/10.1586/14760584.7.1.7 PMID:18251687
   PubMed Web of Science ®Google Scholar
• Petrovsky N. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs. Drug Safety. 2015;38:1059–74. https://doi.org/10.1007/s40264-015-0350-4 PMID:26446142
   PubMed Web of Science ®Google Scholar
• Honda-Okubo Y, Saade F, Petrovsky N. Advax™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine. 2012;30(36):5373-81.
   Google Scholar
• Da Costa AC, Resende DP, Santos BPO, Zoccal KF, Faccioli LH, Kipnis A, Junqueira-Kipnis AP. Modulation of macrophage responses by CMX, a fusion protein composed of Ag85c, MPT51, and HspX From Mycobacterium tuberculosis. Front Microbiol 2017;8:623.of adaptive immune responses. Vaccine. 2017;30:5373–81.
   Google Scholar
• Trentini MM, Oliveira FM, Kipnis A, Junqueira-Kipnis AP. The role of neutrophils in the induction of specific Th1 and Th17 during vaccination against tuberculosis. Front Microbiol. 2016;7:898. https://doi.org/10.3389/fmicb.2016.00898 PMID:27375607
   PubMed Web of Science ®Google Scholar
• Tamburini BA, Burchill MA, Kedl RM. Antigen capture and archiving by lymphatic endothelial cells following vaccination or viral infection. Nat Commun. 2014;5:3989. https://doi.org/10.1038/ncomms4989 PMID:24905362
   PubMed Web of Science ®Google Scholar
• Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993;178:2249–54. https://doi.org/10.1084/jem.178.6.2249 PMID:7504064
   PubMed Web of Science ®Google Scholar
• Bourque SL, Davidge ST, Adams MA. The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol Regul Integr Comp Physiol. 2011;300:R1288–95. https://doi.org/10.1152/ajpregu.00397.2010 PMID:21368267
   PubMed Web of Science ®Google Scholar
• Garcia-Pelayo MC, Bachy VS, Kaveh DA, Hogarth PJ. BALB/c mice display more enhanced BCG vaccine induced Th1 and Th17 response than C57BL/6 mice but have equivalent protection. Tuberculosis (Edinb). 2015;95:48–53. https://doi.org/10.1016/j.tube.2014.10.012 PMID:25467292
   PubMed Web of Science ®Google Scholar
• Maroof A, Yorgensen YM, Li Y, Evans JT. Intranasal vaccination promotes detrimental Th17-Mediated immunity against influenza infection. PLoS Pathog. 2014;10:e1003875. https://doi.org/10.1371/journal.ppat.1003875 PMID:24465206
   PubMed Web of Science ®Google Scholar
• Liu W, Xu Y, Yan J, Shen H, Yang E, Wang H. Ag85B synergizes with ESAT-6 to induce efficient and long-term immunity of C57BL/6 mice primed with recombinant Bacille Calmette-Guerin. Exp Ther Med. 2017;13:208–214. PMID:28123491
   PubMed Web of Science ®Google Scholar
• Reither K, Katsoulis L, Beattie T, Gardiner N, Lenz N, Said K, Mfinanga E, Pohl C, Fielding KL, Jeffery H, et al. Safety and immunogenicity of H1/IC31®, 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. 2014;9:e114602. https://doi.org/10.1371/journal.pone.0114602 PMID:25490675
   PubMed Web of Science ®Google Scholar
• Sreejit G, Ahmed A, Parveen N, Jha V, Valluri VL, Ghosh S, Mukhopadhyay S. The ESAT-6 protein of Mycobacterium tuberculosis interacts with beta-2-microglobulin (β2M) affecting antigen presentation function of macrophage. PLoS Pathog. 2014;10:e1004446. https://doi.org/10.1371/journal.ppat.1004446 PMID:25356553
   PubMed Web of Science ®Google Scholar
• Singh V, Kaur C, Chaudhary VK, Rao KV, Chatterjee S. M. tuberculosis secretory protein ESAT-6 induces metabolic flux perturbations to drive foamy macrophage differentiation. Sci Rep. 2015;5:12906. https://doi.org/10.1038/srep12906 PMID:26250836
   PubMedGoogle Scholar