Intranasal vaccination with protein bodies elicit strong protection against Streptococcus pneumoniae colonization

• DOI: 10.1016/j.vaccine.2021.10.006
• Publication Date: 2021-10-25T13:43:10Z
• Authors: L.F. van Beek; J.D. Langereis; H.B. van den Berg...; J. Gillard; W.S.P. Jong; F.J. van Opzeeland; R. Mesman; L. van Niftrik; I. Joosten; D.A. Diavatopoulos; J. Luirink; M.I. de Jonge
• Keywords: Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Colonization; 0303 health sciences; Vaccination; Radboud University Medical Center; Intranasal vaccine; Antibodies, Bacterial; Pneumococcal Infections; 3. Good health; Pneumococcal Vaccines; Mice; 03 medical and health sciences; Laboratory Medicine - Radboud University Medical Center; Streptococcus pneumoniae; SDG 3 - Good Health and Well-being; Bacterial Proteins; Ecological Microbiology; Animals; Paediatrics - Radboud University Medical Center; Radboudumc 5: Inflammatory diseases RIMLS: Radboud Institute for Molecular Life Sciences; Protein bodies; Immunity, Mucosal; Administration, Intranasal

Protein bodies (PBs) are particles consisting of insoluble, aggregated proteins with potential as a vaccine formulation. PBs can contain high concentrations of antigen, are stable and relatively resistant to proteases, release antigen slowly and are cost-effective to manufacture. Yet, the capacity of PBs to provoke immune responses and protection in the upper respiratory tract, a major entry route of respiratory pathogens, is largely unknown. In this study, we vaccinated mice intranasally with PBs comprising antigens from Streptococcus pneumoniae and evaluated the level of protection against nasopharyngeal colonization. PBs composed of the α-helical domain of pneumococcal surface protein A (PspAα) provided superior protection against colonization with S. pneumoniae compared to soluble PspAα. Immunization with soluble protein or PBs induced differences in antibody binding to pneumococci as well as a highly distinct antigen-specific nasal cytokine profile upon in vivo stimulation with inactivated S. pneumoniae. Moreover, immunization with PBs composed of conserved putative pneumococcal antigens reduced colonization by S. pneumoniae in mice, both as a single- and as a multi-antigen formulation. In conclusion, PBs represent a vaccine formulation that elicits strong mucosal immune responses and protection. The versatility of this platform offers opportunities for development of next-generation vaccine formulations.