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A novel strategy to protect against influenza-induced pneumococcal disease without interfering with commensal colonization

Greene, Christopher J.; Marks, Laura R.; Hu, John C.; Reddinger, Ryan; Mandell, Lorrie; Roche-Hakansson, Hazeline; King-Lyons, Natalie D.; Connell, Terry D. and Håkansson, Anders P LU (2016) In Infection and Immunity 84(6). p.1693-1703
Abstract

Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype-replacement with, so-far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes,... (More)

Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype-replacement with, so-far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virally-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally-induced, pneumococcal disease can be conferred without disturbing the desirable pre-existing commensal colonization of the nasopharynx.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pneumococcal disease
in
Infection and Immunity
volume
84
issue
6
pages
1693 - 1703
publisher
American Society for Microbiology
external identifiers
  • scopus:84971526214
  • wos:000377106900003
ISSN
1098-5522
DOI
10.1128/IAI.01478-15
language
English
LU publication?
yes
id
f0a57bdb-dbc5-4248-8a31-3078be1656ee
date added to LUP
2016-04-12 15:22:46
date last changed
2019-11-17 04:26:56
@article{f0a57bdb-dbc5-4248-8a31-3078be1656ee,
  abstract     = {<p>Streptococcus pneumoniae commonly inhabits the nasopharynx as a member of the commensal biofilm. Infection with respiratory viruses, such as influenza A virus, induces commensal S. pneumoniae to disseminate beyond the nasopharynx and to elicit severe infections of the middle ears, lungs, and blood that are associated with high rates of morbidity and mortality. Current preventive strategies, including the polysaccharide conjugate vaccines aim to eliminate asymptomatic carriage with vaccine-type pneumococci. However, this has resulted in serotype-replacement with, so-far, less fit pneumococcal strains, which has changed the nasopharyngeal flora, opening the niche for entry of other virulent pathogens (e.g., Streptococcus pyogenes, Staphylococcus aureus, and potentially Haemophilus influenzae). The long-term effects of these changes are unknown. Here, we present an attractive, alternative preventive approach where we subvert virally-induced pneumococcal disease without interfering with commensal colonization, thus specifically targeting disease-causing organisms. In that regard, pneumococcal surface protein A (PspA), a major surface protein of pneumococci, is a promising vaccine target. Intradermal (i.d.) immunization of mice with recombinant PspA in combination with LT-IIb(T13I), a novel i.d. adjuvant of the type II heat-labile enterotoxin family, elicited strong systemic PspA-specific IgG responses without inducing mucosal anti-PspA IgA responses. This response protected mice from otitis media, pneumonia, and septicemia and averted the cytokine storm associated with septic infection but had no effect on asymptomatic colonization. Our results firmly demonstrated that this immunization strategy against virally-induced, pneumococcal disease can be conferred without disturbing the desirable pre-existing commensal colonization of the nasopharynx.</p>},
  author       = {Greene, Christopher J. and Marks, Laura R. and Hu, John C. and Reddinger, Ryan and Mandell, Lorrie and Roche-Hakansson, Hazeline and King-Lyons, Natalie D. and Connell, Terry D. and Håkansson, Anders P},
  issn         = {1098-5522},
  keyword      = {pneumococcal disease },
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {1693--1703},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {A novel strategy to protect against influenza-induced pneumococcal disease without interfering with commensal colonization},
  url          = {http://dx.doi.org/10.1128/IAI.01478-15},
  volume       = {84},
  year         = {2016},
}