Advax Augments B and T Cell Responses Upon Influenza Vaccination Via the Respiratory Tract and Enables Complete Protection of Mice Against Lethal Influenza Virus Challenge

Overview

Journal J Control Release

Specialty Pharmacology

Date 2018 Sep 16

PMID 30218687

Citations 25

Authors

Jasmine Tomar

Harshad P Patil

Gustavo Bracho

Wouter F Tonnis

Henderik W Frijlink

Nikolai Petrovsky

Rita Vanbever

Anke Huckriede

Wouter L J Hinrichs

Affiliations

Soon will be listed here.

Abstract

Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.

Citing Articles

Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a cellular receptor for delta inulin adjuvant.

Stewart E, Counoupas C, Steain M, Ashley C, Alca S, Hartley-Tassell L Immunol Cell Biol. 2024; 102(7):593-604.

PMID: 38757764 PMC: 11296934. DOI: 10.1111/imcb.12774.

Lung IL-17A-Producing CD4 T Cells Correlate with Protection after Intrapulmonary Vaccination with Differentially Adjuvanted Tuberculosis Vaccines.

Stewart E, Counoupas C, Quan D, Wang T, Petrovsky N, Britton W Vaccines (Basel). 2024; 12(2).

PMID: 38400112 PMC: 10892942. DOI: 10.3390/vaccines12020128.

Prolonging the delivery of influenza virus vaccine improves the quantity and quality of the induced immune responses in mice.

Beukema M, Gong S, Al-Jaawni K, de Vries-Idema J, Krammer F, Zhou F Front Immunol. 2023; 14:1249902.

PMID: 37869002 PMC: 10585035. DOI: 10.3389/fimmu.2023.1249902.

Methionine enkephalin(MENK) upregulated memory T cells in anti-influenza response.

Tian J, Fu W, Xie Z, Wang X, Miao M, Shan F BMC Immunol. 2023; 24(1):38.

PMID: 37828468 PMC: 10571428. DOI: 10.1186/s12865-023-00573-0.

Nanotechnology of inhalable vaccines for enhancing mucosal immunity.

Qin L, Sun Y, Gao N, Ling G, Zhang P Drug Deliv Transl Res. 2023; 14(3):597-620.

PMID: 37747597 DOI: 10.1007/s13346-023-01431-7.

References

Stary G, Olive A, Radovic-Moreno A, Gondek D, Alvarez D, Basto P . VACCINES. A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells. Science. 2015; 348(6241):aaa8205. PMC: 4605428. DOI: 10.1126/science.aaa8205. View

Gordon D, Sajkov D, Woodman R, Honda-Okubo Y, Cox M, Heinzel S . Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax™ polysaccharide adjuvant. Vaccine. 2012; 30(36):5407-16. PMC: 3410954. DOI: 10.1016/j.vaccine.2012.06.009. View

Smieszek T, Lazzari G, Salathe M . Assessing the Dynamics and Control of Droplet- and Aerosol-Transmitted Influenza Using an Indoor Positioning System. Sci Rep. 2019; 9(1):2185. PMC: 6379436. DOI: 10.1038/s41598-019-38825-y. View

Waldman R, Mann J, Small Jr P . Immunization against influenza. Prevention of illness in man by aerosolized inactivated vaccine. JAMA. 1969; 207(3):520-4. DOI: 10.1001/jama.207.3.520. View

Kohlmeier J, Cookenham T, Miller S, Roberts A, Christensen J, Thomsen A . CXCR3 directs antigen-specific effector CD4+ T cell migration to the lung during parainfluenza virus infection. J Immunol. 2009; 183(7):4378-84. PMC: 2757292. DOI: 10.4049/jimmunol.0902022. View

Honda-Okubo Y, Barnard D, Ong C, Peng B, Tseng C, Petrovsky N . Severe acute respiratory syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while ameliorating lung eosinophilic immunopathology. J Virol. 2014; 89(6):2995-3007. PMC: 4337527. DOI: 10.1128/JVI.02980-14. View

Moran T, Park H, Fernandez-Sesma A, SCHULMAN J . Th2 responses to inactivated influenza virus can Be converted to Th1 responses and facilitate recovery from heterosubtypic virus infection. J Infect Dis. 1999; 180(3):579-85. DOI: 10.1086/314952. View

Layton R, Petrovsky N, Gigliotti A, Pollock Z, Knight J, Donart N . Delta inulin polysaccharide adjuvant enhances the ability of split-virion H5N1 vaccine to protect against lethal challenge in ferrets. Vaccine. 2011; 29(37):6242-51. PMC: 3156374. DOI: 10.1016/j.vaccine.2011.06.078. View

Tomar J, Born P, Frijlink H, Hinrichs W . Dry influenza vaccines: towards a stable, effective and convenient alternative to conventional parenteral influenza vaccination. Expert Rev Vaccines. 2016; 15(11):1431-1447. DOI: 10.1080/14760584.2016.1182869. View

10.

Graham M, Braciale T . Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice. J Exp Med. 1998; 186(12):2063-8. PMC: 2199163. DOI: 10.1084/jem.186.12.2063. View

11.

Bungener L, Geeraedts F, ter Veer W, Medema J, Wilschut J, Huckriede A . Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection. Vaccine. 2008; 26(19):2350-9. DOI: 10.1016/j.vaccine.2008.02.063. View

12.

Huber V, McKeon R, Brackin M, Miller L, Keating R, Brown S . Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol. 2006; 13(9):981-90. PMC: 1563571. DOI: 10.1128/CVI.00156-06. View

13.

Ridderstad A, Tarlinton D . Kinetics of establishing the memory B cell population as revealed by CD38 expression. J Immunol. 1998; 160(10):4688-95. View

14.

McKinstry K, Strutt T, Swain S . The potential of CD4 T-cell memory. Immunology. 2010; 130(1):1-9. PMC: 2855787. DOI: 10.1111/j.1365-2567.2010.03259.x. View

15.

van Riet E, Ainai A, Suzuki T, Hasegawa H . Mucosal IgA responses in influenza virus infections; thoughts for vaccine design. Vaccine. 2012; 30(40):5893-900. DOI: 10.1016/j.vaccine.2012.04.109. View

16.

Liu H, Patil H, De Vries-Idema J, Wilschut J, Huckriede A . Enhancement of the immunogenicity and protective efficacy of a mucosal influenza subunit vaccine by the saponin adjuvant GPI-0100. PLoS One. 2013; 7(12):e52135. PMC: 3524133. DOI: 10.1371/journal.pone.0052135. View

17.

Wang L, Barclay T, Song Y, Joyce P, Sakala I, Petrovsky N . Investigation of the biodistribution, breakdown and excretion of delta inulin adjuvant. Vaccine. 2017; 35(34):4382-4388. DOI: 10.1016/j.vaccine.2017.06.045. View

18.

Shin H, Iwasaki A . A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature. 2012; 491(7424):463-7. PMC: 3499630. DOI: 10.1038/nature11522. View

19.

Cooper P, Petrovsky N . Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers. Glycobiology. 2010; 21(5):595-606. PMC: 3106373. DOI: 10.1093/glycob/cwq201. View

20.

Patil H, Murugappan S, ter Veer W, Meijerhof T, de Haan A, Frijlink H . Evaluation of monophosphoryl lipid A as adjuvant for pulmonary delivered influenza vaccine. J Control Release. 2013; 174:51-62. DOI: 10.1016/j.jconrel.2013.11.013. View