Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans
Ang Lin, Danijela Apostolovic, Maja Jahnmatz, Frank Liang, Sebastian Ols, Teghesti Tecleab, Chenyan Wu, Marianne van Hage, Ken Solovay, Keith Rubin, Camille Locht, Rigmor Thorstensson, Marcel Thalen, Karin Loré
Ang Lin, Danijela Apostolovic, Maja Jahnmatz, Frank Liang, Sebastian Ols, Teghesti Tecleab, Chenyan Wu, Marianne van Hage, Ken Solovay, Keith Rubin, Camille Locht, Rigmor Thorstensson, Marcel Thalen, Karin Loré
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Clinical Research and Public Health Immunology

Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans

Abstract

BACKGROUND The live attenuated BPZE1 vaccine candidate induces protection against B. pertussis and prevents nasal colonization in animal models. Here we report on the responses in humans receiving a single intranasal administration of BPZE1.METHODS We performed multiple assays to dissect the immune responses induced in humans (n = 12) receiving BPZE1, with particular emphasis on the magnitude and characteristics of the antibody responses. Such responses were benchmarked to adolescents (n = 12) receiving the complete vaccination program of the currently used acellular pertussis vaccine (aPV). Using immunoproteomics analysis, potentially novel immunogenic B. pertussis antigens were identified.RESULTS All BPZE1 vaccinees showed robust B. pertussis–specific antibody responses with regard to significant increase in 1 or more of the following parameters: IgG, IgA, and memory B cells to B. pertussis antigens. BPZE1–specific T cells showed a Th1 phenotype, and the IgG exclusively consisted of IgG1 and IgG3. In contrast, all aPV vaccines showed a Th2-biased response. Immunoproteomics profiling revealed that BPZE1 elicited broader and different antibody specificities to B. pertussis antigens as compared with the aPV that primarily induced antibodies to the vaccine antigens. Moreover, BPZE1 was superior at inducing opsonizing antibodies that stimulated ROS production in neutrophils and enhanced bactericidal function, which was in line with the finding that antibodies against adenylate cyclase toxin were only elicited by BPZE1.CONCLUSION The breadth of the antibodies, the Th1-type cellular response, and killing mechanisms elicited by BPZE1 may hold prospects of improving vaccine efficacy and protection against B. pertussis transmission.TRIAL REGISTRATION ClinicalTrials.gov NCT02453048, NCT00870350.FUNDING ILiAD Biotechnologies, Swedish Research Council (Vetenskapsrådet), Swedish Heart-Lung Foundation.

Authors

Ang Lin, Danijela Apostolovic, Maja Jahnmatz, Frank Liang, Sebastian Ols, Teghesti Tecleab, Chenyan Wu, Marianne van Hage, Ken Solovay, Keith Rubin, Camille Locht, Rigmor Thorstensson, Marcel Thalen, Karin Loré

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Figure 2

BPZE1 vaccination induced robust antibody titers and Th1–biased CD4+ T cell responses.

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BPZE1 vaccination induced robust antibody titers and Th1–biased CD4+ T c...
(A and B) Antibody responses directed against BPZE1 or BP611-98 lysates in BPZE1 vaccinees (n = 12) at different time points after vaccination. Wilcoxon matched-pairs signed-rank test was used. (C) Correlation of IgG or IgA responses directed against BPZE1 lysates with that directed against B611-98 lysates. Pearson’s correlation analysis was used. (D) Protein fingerprints of BPZE1 and BP611-98 by 2D PAGE. Gels were stained with colloidal Coomassie Brilliant Blue (CBB) G-250. Four independent experiments were performed and one representative gel is shown. (E) Representative gating of CD4+ memory T cell populations. (F) PBMCs collected before and at 28 days after vaccination from BPZE1 vaccinees (n = 11) or placebo subjects (n = 7) were stimulated with heat-inactivated BPZE1 (bacteria/cell ratio = 10:1). Cells treated with Staphylococcus enterotoxin B were used as a positive control. Levels of the indicated cytokine–producing memory CD4+ T cells were analyzed. Data from one representative donor are shown. (G) Quantification of cytokine-producing CD4+ memory T cells following heat–inactivated BPZE1 stimulation in BPZE1 vaccinees (n = 11) and placebo subjects (n = 7). Negative control (PBS) values were subtracted. Two-tailed paired t test was used. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.