Intranasal vaccination with γ-irradiated Streptococcus pneumoniae whole-cell vaccine provides serotype-independent protection mediated by B-cells and innate IL-17 responses

Clin Sci (Lond). 2016 May;130(9):697-710. doi: 10.1042/CS20150699. Epub 2016 Feb 1.

Abstract

Generating a pneumococcal vaccine that is serotype independent and cost effective remains a global challenge. γ-Irradiation has been used widely to sterilize biological products. It can also be utilized 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 utilized γ-irradiation to inactivate an un-encapsulated Streptococcus 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 γ-PN vaccine). Intranasal vaccination of C57BL/6 mice with γ-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 interleukin (IL)-17A responses. Interestingly, immunization promoted IL-17 production by innate cells not T helper 17 (Th17) cells. These data are the first to report the development of a non-adjuvanted intranasal γ-irradiated pneumococcal vaccine that generates effective serotype-independent protection, which is mediated by both humoral and innate IL-17 responses.

Keywords: Streptococcus pneumoniae; protective immunity; serotype independent; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Gamma Rays*
  • Immunity, Innate* / immunology
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism*
  • Mice, Inbred C57BL
  • Pneumococcal Infections / complications
  • Pneumococcal Infections / immunology
  • Pneumococcal Infections / microbiology
  • Pneumococcal Infections / prevention & control
  • Pneumococcal Vaccines / administration & dosage
  • Pneumococcal Vaccines / immunology*
  • Sepsis / complications
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / prevention & control
  • Serotyping
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / immunology*
  • Streptococcus pneumoniae / radiation effects*
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vaccination*

Substances

  • Interleukin-17
  • Pneumococcal Vaccines
  • Interferon-gamma