Live attenuated pertussis vaccine BPZE1 induces a broad antibody response in humans
Ang Lin, … , Marcel Thalen, Karin Loré
Ang Lin, … , Marcel Thalen, Karin Loré
Published January 16, 2020
Citation Information: J Clin Invest. 2020;130(5):2332-2346. https://doi.org/10.1172/JCI135020.
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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 6

BPZE1 was superior to aPV at inducing opsonizing antibodies leading to enhanced neutrophil bactericidal activity.

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BPZE1 was superior to aPV at inducing opsonizing antibodies leading to e...
(A–E) Fresh human neutrophils (106 cells) were infected with live BPZE1 (107 CFU) or BPZE1 opsonized by pooled serum of BPZE1 or aPV vaccinees for 1 hour. ROS production and expression of activation/maturation markers were evaluated. Compiled data are from at least 3 independent experiments. (A) 10% pooled serum of BPZE1 vaccinees (n = 12) were used. Cells without stimulation or cultured with pooled serum alone were used as control. MFI values of the indicated markers are shown. Two-tailed paired t test was used. (B) Different concentrations of serum collected from BPZE1 vaccinees were evaluated. (C) Pooled serum of BPZE1 vaccinees collected at different time points were evaluated. Two-tailed paired t test was used. (D) Pooled serum of BPZE1 or aPV vaccinees were evaluated and compared side by side. (E) Different concentrations of serum collected from aPV vaccinees were evaluated. (F) Antibody titers of IgG, IgA, IgG1, and IgG3 targeting ACT were measured in BPZE1 and aPV vaccinees (n = 12). Two-tailed Wilcoxon matched-pairs signed-rank test was used. (G) Neutrophils were infected with live BPZE1 opsonized by 10% pooled serum or HI serum of BPZE1 vaccinees for 1 hour. ROS production was evaluated. Compiled data from 4 independent experiments are shown. (H) The effect of opsonization-mediated ROS production on the bactericidal activity of neutrophils was evaluated in vitro. Compiled data are from 4 independent experiments. Two-tailed paired t test was used. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001.