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 Medicine Immunology Vaccines

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 1

Expansion of plasmablasts and activated cTfh1 cells following BPZE1 vaccination.

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Expansion of plasmablasts and activated cTfh1 cells following BPZE1 vacc...
(A) Phenotypic identification of circulating plasmablasts according to the depicted gating strategy. (B) Frequency of plasmablasts at different time points following BPZE1 vaccination. Data from one representative BPZE1 vaccinee are shown. Dot plots show number of plasmablasts per million PBMCs. (C) Phenotypic identification of activated cTfh cells according to the depicted gating strategy. (D) Frequency of activated cTfh1 and cTfh2/17 cells at different time points following BPZE1 vaccination. Data from one representative BPZE1 vaccinee are shown (upper panel). Dot plots show number of cells per million PBMCs (lower panel) (n = 12 for BPZE1 group and n = 10 for placebo group). (E) Surface expression of indicated markers on PD1+ICOS+, PD1+ICOS–, and PD1–ICOS– cTfh1 cells. Mean fluorescence intensity (MFI) values of markers are shown. Two-tailed Wilcoxon matched-pairs signed-rank test was used for all compiled data. **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.