Gamma-irradiation of Streptococcus pneumoniae for the use as an immunogenic whole cell vaccine

Abstract

Streptococcus pneumoniae is a major respiratory pathogen that causes millions of deaths worldwide. Although subunit vaccines formulated with the capsular polysaccharides or their protein conjugates are currently-available, low-cost vaccines with wide serotype coverage still remain to be developed, especially for developing countries. Recently, gamma- irradiation has been considered as an effective inactivation method to prepare S. pneumoniae vaccine candidate. In this study, we investigated the immunogenicity and protective immunity of gamma-irradiated S. pneumoniae (r-SP), by comparing with heat-inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP), both of which were made by traditional inactivation methods. Intranasal immunization of C57BL/6 mice with r-SP in combination with cholera toxin as an adjuvant enhanced S. pneumoniaespecific antibodies on the airway mucosal surface and in sera more potently than that with h-SP or f-SP under the same conditions. In addition, sera from mice immunized with r-SP potently induced opsonophagocytic killing activity more effectively than those of h-SP or f-SP, implying that r-SP could induce protective antibodies. Above all, immunization with r-SP effectively protected mice against S. pneumoniae infection. Collectively, these results suggest that gamma- irradiation is an effective method for the development of a killed whole cell pneumococcal vaccine that elicits robust mucosal and systemic immune responses.

Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy

“…Ionizing radiation has been used to generate bacterial vaccines that elicited protective immune responses in several studies [7][8][9][10]23]. In line with this, our data showed that LEEI has clear advantages over formaldehyde in respect to the conservation of antigenicity in the inactivation process.…”

“…As an alternative strategy to chemical treatment, ionizing radiation has been used to generate a variety of experimental bacterial vaccines with promising results [7][8][9][10]. It inactivates by damaging nucleic acids, leaving structural components such as proteins largely intact [11,12].…”

Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities

“…In contrast, few inactivation technologies leave the structural components largely intact, so that the material can be used e.g. as vaccines, in diagnostics or in therapeutic strategies 1 – 3 .…”

“…Consequently, irradiated viruses or bacteria are highly efficient as vaccines against a variety of human or animal infections, and the technology can be used to inactivate pathogens in various biological samples 9 – 11 . There are several advantages over chemical inactivation (currently the only way to produce inactivated vaccines), including the lack of toxic chemicals like formaldehyde, high reproducibility, high conservation of antigenic content and short reaction time 3 , 9 , 12 – 14 .…”

Next-Generation Whole-Cell Pneumococcal Vaccine

“…Currently, investigations are focused on gaining a better understanding of the immunological mechanism involved in PWCV protection and providing improvements in the vaccine formulation through bacterial inactivation by gamma irradiation [48,[57][58][59][60].…”