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Comparison of four adjuvants revealed the strongest protection against lethal pneumococcal challenge following immunization with PsaA-PspA fusion protein and AS02 as adjuvant

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Abstract

Streptococcuspneumoniae, or pneumococcus, is a major respiratory-tract pathogen that causes high levels of mortality and morbidity in infants and elderly individuals. Despite the development of various capsular polysaccharide vaccines to prevent pneumococcal disease, it remains epidemic. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein existing in all strains of S. pneumoniae, and it can elicit immunizing protection against pneumococcal infection. In our previous studies, a fusion protein (PsaA-PspA23), consisting of PspA and pneumococcal surface antigen A (PsaA), displayed greater immunogenicity and provided better protection in mice against S. pneumoniae strains than either PsaA or PspA. In this study, the fusion protein PsaA-PspA23, together with PspA4, was formulated with four adjuvants Al(OH)3, MF59, AS03, and AS02, and subsequently subjected to dose optimization and immunological evaluation for determination of the antibody titers, bacterial burden, survival rates, and levels of cytokines in mice. All vaccines with high adjuvant doses displayed higher antigen-specific immunoglobulin G (IgG) titers. Bacterial burdens were notably decreased to different extents in the lungs and blood of mice immunized with the antigen and various adjuvants. Among these adjuvants, AS02 provided outstanding protection against challenge with pathogenic bacteria from different families and clades; it also induced high titers of IgG1 and IgG2a. Moreover, only AS02 elicited high levels of cytokines, such as TNF-α, IFN-γ, IL-2, and IL-4. These results suggest that PsaA-PspA23 and PspA4 formulated with AS02 may potentially be used as a subunit vaccine against deadly pneumococcal infection.

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Acknowledgements

We are grateful for support from Jilin Provincial Industrial Innovation Special Project for the New Vaccine Adjuvant Innovation Technology Platform (Grant No. 2018C004).

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China

    Xiaorui Chen, Bo Li, Jinfei Yu, Yue Zhang, Zujian Mo, Tiejun Gu, Wei Kong, Yong Zhang & Yongge Wu

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  1. Xiaorui Chen
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  2. Bo Li
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Correspondence to Yong Zhang or Yongge Wu.

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All mouse experiments in this paper were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council).

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Edited by: B. Opitz.

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Chen, X., Li, B., Yu, J. et al. Comparison of four adjuvants revealed the strongest protection against lethal pneumococcal challenge following immunization with PsaA-PspA fusion protein and AS02 as adjuvant. Med Microbiol Immunol 208, 215–226 (2019). https://doi.org/10.1007/s00430-019-00579-9

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