rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine VectorReport as inadecuate




rBCG Induces Strong Antigen-Specific T Cell Responses in Rhesus Macaques in a Prime-Boost Setting with an Adenovirus 35 Tuberculosis Vaccine Vector - Download this document for free, or read online. Document in PDF available to download.

Background

BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis TB. We tested BCG SSI1331 in 6 animals, delivered intradermally and a recombinant rBCG AFRO-1 expressing perfringolysin in 6 animals followed by two boosts delivered intramuscullary with non-replicating adenovirus 35 rAd35 expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques Macaca mulatta. Control animals received diluent 3 animals.

Methods and Findings

Cellular immune responses were analyzed longitudinally 12 blood draws for each animal using intracellular cytokine staining TNF-alpha, IL-2 and IFN-gamma, T cell proliferation was measured in CD4+, CD8alpha-beta+, and CD8alpha-alpha+ T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures whole blood cell assay, WBA using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i increased Ag85B-specific IFN-gamma production in the WBA assay median >400 pg-ml for 6 animals one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG <200 pg-ml, ii stronger T cell proliferation in the CD8alpha-alpha+ T cell subset proliferative index 17% as compared to BCG-primed animals proliferative index 5% in CD8alpha-alpha+ T cells. Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2-6 animals primed with AFRO-1 directed against Ag85A-b and TB10.4; 4-6 animals primed with BCG showed a Ag85A-b responses, yet only a single animal exhibited Ag85A-b and TB10.4 reactivity.

Conclusion

AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell proliferation in the CD8alpha-alpha+ T cell subset represents a valuable marker for vaccine-take in BCG-based TB vaccine trials



Author: Isabelle Magalhaes, Donata R. Sizemore, Raija K. Ahmed, Stefanie Mueller, Lena Wehlin, Charles Scanga, Frank Weichold, Giulia Sch

Source: http://plos.srce.hr/



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