Enhancement of Antituberculosis Immunity in a Humanized Model System by a Novel Virus-Vectored Respiratory Mucosal Vaccine

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2017 May 23

PMID 28531291

Citations 10

Authors

Yushi Yao

Rocky Lai

Sam Afkhami

Siamak Haddadi

Anna Zganiacz

Fatemeh Vahedi

Ali A Ashkar

Charu Kaushic

Mangalakumari Jeyanathan

Zhou Xing

Affiliations

Soon will be listed here.

Abstract

Background: The translation of preclinically promising novel tuberculosis vaccines to ultimate human applications has been challenged by the lack of animal models with an immune system equivalent to the human immune system in its genetic diversity and level of susceptibility to tuberculosis.

Methods: We have developed a humanized mice (Hu-mice) tuberculosis model system to investigate the clinical relevance of a novel virus-vectored (VV) tuberculosis vaccine administered via respiratory mucosal or parenteral route.

Results: We find that VV vaccine activates T cells in Hu-mice as it does in human vaccinees. The respiratory mucosal route for delivery of VV vaccine in Hu-mice, but not the parenteral route, significantly reduces the humanlike lung tuberculosis outcomes in a human T-cell-dependent manner.

Conclusions: Our results suggest that the Hu-mouse can be used to predict the protective efficacy of novel tuberculosis vaccines/strategies before they proceed to large, expensive human trials. This new vaccine testing system will facilitate the global pace of clinical tuberculosis vaccine development.

Citing Articles

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Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice.

Afkhami S, DAgostino M, Vaseghi-Shanjani M, Lepard M, Yang J, Lai R NPJ Vaccines. 2023; 8(1):25.

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Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/ Co-Infection Studies.

Lepard M, Yang J, Afkhami S, Nazli A, Zganiacz A, Tang S Viruses. 2022; 14(9).

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Advancing Immunotherapeutic Vaccine Strategies Against Pulmonary Tuberculosis.

Afkhami S, Villela A, DAgostino M, Jeyanathan M, Gillgrass A, Xing Z Front Immunol. 2020; 11:557809.

PMID: 33013927 PMC: 7509172. DOI: 10.3389/fimmu.2020.557809.

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OConnell A, Douam F Vaccines (Basel). 2020; 8(1).

PMID: 31973073 PMC: 7157703. DOI: 10.3390/vaccines8010036.

References

Jeyanathan M, Damjanovic D, Yao Y, Bramson J, Smaill F, Xing Z . Induction of an Immune-Protective T-Cell Repertoire With Diverse Genetic Coverage by a Novel Viral-Vectored Tuberculosis Vaccine in Humans. J Infect Dis. 2016; 214(12):1996-2005. PMC: 5142089. DOI: 10.1093/infdis/jiw467. View

Getahun H, Matteelli A, Chaisson R, Raviglione M . Latent Mycobacterium tuberculosis infection. N Engl J Med. 2015; 372(22):2127-35. DOI: 10.1056/NEJMra1405427. View

Ferreira D, Moreno A, Cianciarullo A, Ho P, Oliveira M, Miyaji E . Comparison of the pulmonary response against lethal and non-lethal intranasal challenges with two different pneumococcal strains. Microb Pathog. 2009; 47(3):157-63. DOI: 10.1016/j.micpath.2009.05.005. View

Dykstra C, Lee A, Lusty E, Shenouda M, Shafai M, Vahedi F . Reconstitution of immune cell in liver and lymph node of adult- and newborn-engrafted humanized mice. BMC Immunol. 2016; 17(1):18. PMC: 4910253. DOI: 10.1186/s12865-016-0157-9. View

Urdahl K, Shafiani S, Ernst J . Initiation and regulation of T-cell responses in tuberculosis. Mucosal Immunol. 2011; 4(3):288-93. PMC: 3206635. DOI: 10.1038/mi.2011.10. View

Andersen P, Kaufmann S . Novel vaccination strategies against tuberculosis. Cold Spring Harb Perspect Med. 2014; 4(6). PMC: 4031959. DOI: 10.1101/cshperspect.a018523. View

Cooper A . T cells in mycobacterial infection and disease. Curr Opin Immunol. 2009; 21(4):378-84. PMC: 2746551. DOI: 10.1016/j.coi.2009.06.004. View

Bhatt K, Verma S, Ellner J, Salgame P . Quest for correlates of protection against tuberculosis. Clin Vaccine Immunol. 2015; 22(3):258-66. PMC: 4340894. DOI: 10.1128/CVI.00721-14. View

Jeyanathan M, Shao Z, Yu X, Harkness R, Jiang R, Li J . AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates. PLoS One. 2015; 10(8):e0135009. PMC: 4529167. DOI: 10.1371/journal.pone.0135009. View

10.

Calderon V, Valbuena G, Goez Y, Judy B, Huante M, Sutjita P . A humanized mouse model of tuberculosis. PLoS One. 2013; 8(5):e63331. PMC: 3656943. DOI: 10.1371/journal.pone.0063331. View

11.

Xing Z, McFarland C, Sallenave J, Izzo A, Wang J, McMurray D . Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis. PLoS One. 2009; 4(6):e5856. PMC: 2689939. DOI: 10.1371/journal.pone.0005856. View

12.

Lee J, Brehm M, Greiner D, Shultz L, Kornfeld H . Engrafted human cells generate adaptive immune responses to Mycobacterium bovis BCG infection in humanized mice. BMC Immunol. 2013; 14:53. PMC: 3924189. DOI: 10.1186/1471-2172-14-53. View

13.

Brennan M, Thole J . Tuberculosis vaccines: a strategic blueprint for the next decade. Tuberculosis (Edinb). 2012; 92 Suppl 1:S6-13. DOI: 10.1016/S1472-9792(12)70005-7. View

14.

Satti I, Meyer J, Harris S, Manjaly Thomas Z, Griffiths K, Antrobus R . 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. 2014; 14(10):939-46. PMC: 4178237. DOI: 10.1016/S1473-3099(14)70845-X. View

15.

Vordermeier H, Huygen K, Singh M, Hewinson R, Xing Z . Immune responses induced in cattle by vaccination with a recombinant adenovirus expressing Mycobacterial antigen 85A and Mycobacterium bovis BCG. Infect Immun. 2006; 74(2):1416-8. PMC: 1360309. DOI: 10.1128/IAI.74.2.1416-1418.2006. View

16.

Huebner R, Schein M, Bass Jr J . The tuberculin skin test. Clin Infect Dis. 1993; 17(6):968-75. DOI: 10.1093/clinids/17.6.968. View

17.

Myllymaki H, Niskanen M, Oksanen K, Ramet M . Animal models in tuberculosis research - where is the beef?. Expert Opin Drug Discov. 2015; 10(8):871-83. DOI: 10.1517/17460441.2015.1049529. View

18.

Kaushal D, Foreman T, Gautam U, Alvarez X, Adekambi T, Rangel-Moreno J . Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis. Nat Commun. 2015; 6:8533. PMC: 4608260. DOI: 10.1038/ncomms9533. View

19.

Dean G, Clifford D, Whelan A, Tchilian E, Beverley P, Salguero F . Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle. PLoS One. 2015; 10(11):e0142270. PMC: 4636221. DOI: 10.1371/journal.pone.0142270. View

20.

Kaufmann S, McElrath M, Lewis D, Del Giudice G . Challenges and responses in human vaccine development. Curr Opin Immunol. 2014; 28:18-26. DOI: 10.1016/j.coi.2014.01.009. View