Clin Sci (Lond). 2016 Feb 1. pii: CS20150699. [Epub ahead of print]
Generating a pneumococcal vaccine that is serotype-independent and cost effective remains a global challenge. Gamma-irradiation has been used widely to sterilize biological products. It can also be utilised as an inactivation technique to generate whole cell bacterial and viral vaccines with minimal impact on pathogen structure and antigenic determinants. In the present study, we utilised gamma-irradiation to inactivate an unencapsulatedStreptococcus pneumoniae strain Rx1 with an unmarked deletion of the autolysin gene lytA and with the pneumolysin gene ply replaced with an allele encoding a non-toxic pneumolysoid (PdT) (designated g-PN vaccine). Intranasal vaccination of C57BL/6 mice with g-PN was shown to elicit serotype-independent protection in lethal challenge models of pneumococcal pneumonia and sepsis. Vaccine efficacy was shown to be reliant on B cells and IL-17A responses. Interestingly, immunisation promoted IL-17 production by innate cells not Th17 cells. These data are the first to report the development of a non-adjuvanted intranasal gamma-irradiated pneumococcal vaccine that generates effective serotype-independent protection, which is mediated by both humoral and innate IL-17 responses.
Copyright 2016 The Author(s).
PMID: 26831937 [PubMed - as supplied by publisher]