Plant‐derived recombinant immune complexes as self‐adjuvanting TB immunogens for mucosal boosting of BCG

Progress with protein‐based tuberculosis (TB) vaccines has been limited by poor availability of adjuvants suitable for human application. Here, we developed and tested a novel approach to molecular engineering of adjuvanticity that circumvents the need for exogenous adjuvants. Thus, we generated and...

Full description

Saved in:
Bibliographic Details
Published in:Plant biotechnology journal 2014-09, Vol.12 (7), p.840-850
Main Authors: Pepponi, Ilaria, Diogo, Gil R, Stylianou, Elena, Dolleweerd, Craig J, Drake, Pascal M. W, Paul, Matthew J, Sibley, Laura, Ma, Julian K.‐C, Reljic, Rajko
Format: Article
Language:English
Subjects:
Adenoviruses
Adjuvanticity
Adjuvants
Adjuvants, Immunologic - biosynthesis
Adjuvants, Immunologic - metabolism
Administration, Intranasal
Animals
Antibodies
Antibody Formation
antigen-antibody complex
Antigen-Antibody Complex - metabolism
Antigen-antibody complexes
Antigen-presenting cells
Antigens
Biological activity
blood serum
CD4 antigen
CD4-Positive T-Lymphocytes - metabolism
Cell Proliferation
Cell surface
Cloning, Molecular
complement
Complement component C1q
Ebola virus
Genetic engineering
Humans
IgG antibody
immune complexes
Immune response
Immunization
Immunoglobulin G
Immunology
infection
Infections
Interferon
interferon-gamma
Interleukin-2 - metabolism
Latency
lungs
Lymphocytes
Mice
Monoclonal antibodies
Mucosa
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Nicotiana - genetics
Nicotiana - metabolism
phenotype
Phenotypes
Plant extracts
plants
Plants (organisms)
Plants, Genetically Modified - metabolism
Polypeptides
Proteins
Recombinant
Splenocytes
Statistical analysis
Tobacco
Transgenic plants
Tuberculosis
Tuberculosis Vaccines - administration & dosage
Tuberculosis Vaccines - immunology
tumor necrosis factor-alpha
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
vaccine
Vaccines
γ-Interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Request full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Progress with protein‐based tuberculosis (TB) vaccines has been limited by poor availability of adjuvants suitable for human application. Here, we developed and tested a novel approach to molecular engineering of adjuvanticity that circumvents the need for exogenous adjuvants. Thus, we generated and expressed in transgenic tobacco plants the recombinant immune complexes (RICs) incorporating the early secreted Ag85B and the latency‐associated Acr antigen of Mycobacterium tuberculosis, genetically fused as a single polypeptide to the heavy chain of a monoclonal antibody to Acr. The RICs were formed by virtue of the antibody binding to Acr from adjacent molecules, thus allowing self‐polymerization of the complexes. TB‐RICs were purified from the plant extracts and shown to be biologically active by demonstrating that they could bind to C1q component of the complement and also to the surface of antigen‐presenting cells. Mice immunized with BCG and then boosted with two intranasal immunizations with TB‐RICs developed antigen‐specific serum IgG antibody responses with mean end‐point titres of 1 : 8100 (Acr) and 1 : 24 300 (Ag85B) and their splenocytes responded to in vitro stimulation by producing interferon gamma. 25% of CD4+ proliferating cells simultaneously produced IFN‐γ, IL‐2 and TNF‐α, a phenotype that has been linked with protective immune responses in TB. Importantly, mucosal boosting of BCG‐immunized mice with TB‐RICs led to a reduced M. tuberculosis infection in their lungs from log₁₀ mean = 5.69 ± 0.1 to 5.04 ± 0.2, which was statistically significant. We therefore propose that the plant‐expressed TB‐RICs represent a novel molecular platform for developing self‐adjuvanting mucosal vaccines.
ISSN:1467-7644
1467-7652
DOI:10.1111/pbi.12185