title: Cellular immune responses to nine Mycobacterium tuberculosis vaccine candidates following intranasal vaccination.
abstract: BACKGROUND
  The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis.
  
  
  RESULTS
  In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study.
  
  
  CONCLUSIONS
  Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis.
authors.affiliation: Division of TB Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America. ssable@cdc.gov
authors.forename: Suraj B
authors.initials: SB
authors.lastname: Sable
authors.forename: Mani
authors.initials: M
authors.lastname: Cheruvu
authors.forename: Subhadra
authors.initials: S
authors.lastname: Nandakumar
authors.forename: Sunita
authors.initials: S
authors.lastname: Sharma
authors.forename: Kakali
authors.initials: K
authors.lastname: Bandyopadhyay
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Kellar
authors.forename: James E
authors.initials: JE
authors.lastname: Posey
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Plikaytis
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Shinnick
mesh_terms: D000281:Administration, Intranasal; D000409:Alanine; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009569:Nitric Oxide / Q000378:metabolism; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014376:Tuberculosis / Q000517:prevention & control; D014611:Vaccination / Q000379:methods*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D009569:Nitric Oxide; D007371:Interferon-gamma; D000409:Alanine