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

Lin, A;Apostolovic, D;Jahnmatz, M;Liang, F;Ols, S;Tecleab, T;Wu, C;van Hage, M;Solovay, K;Rubin, K;Locht, C;Thorstensson, R;Thalen, M;Lor, K;

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. 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, novel immunogenic B. pertussis antigens were identified. All BPZE1 vaccinees showed robust B. pertussis-specific antibody responses with regard to significant increase in one or more of the 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 vaccinees showed a Th2-biased response. Immunoproteomics profiling revealed that BPZE1 elicited broader and different antibody specificities to B. pertussis antigens as compared to the aPV that primarily induced antibodies to the vaccine antigens. Moreover, BPZE1 was superior at inducing opsonizing antibodies that stimulated reactive oxygen species (ROS) production in neutrophils and enhanced bactericidal function, which was in line with that antibodies against adenylate cyclase toxin were only elicited by BPZE1. 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. NCT02453048, NCT00870350FUNDING. ILiAD Biotechnologies, Swedish Research Council (Vetenskapsrdet), Swedish Heart-lung Foundation.