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.
View: Text | PDF
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

×

Figure 4

Different types of antibody responses were elicited by BPZE1 and aPV immunization.

Options: View larger image (or click on image) Download as PowerPoint
Different types of antibody responses were elicited by BPZE1 and aPV imm...
(A) Immunization schedule for BPZE1 vaccinees (n = 12) and aPV vaccinees (n = 12). (B–D) Antibody titers of IgG, IgA, and 4 IgG subclasses directed against BPZE1 lysates, BP611-98 lysates, and antigen mix in BPZE1 and aPV vaccines were evaluated. OD value is shown. Two-tailed Wilcoxon matched-pairs signed-rank test was used for comparison in the same group. Two-tailed Mann-Whitney test was used for comparison between 2 groups. (E) Antibody avidity of IgG and IgA targeting BPZE1 lysates in BPZE1 and aPV vaccines was evaluated. Avidity index EC50 represents the concentration of chaotropic agent (NH4SCN) that dissociates 50% of the antibody-antigen binding. Two-tailed Mann-Whitney test was used. (F) Ratio of IgG3/IgG2, IgG4/IgG3, and IgG4/IgG1 against BPZE1 lysates at 28 days after vaccination in BPZE1 and aPV vaccinees is shown. Mann-Whitney test was used. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001.