Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae

Gill Douce, Kirsty Ross, Graeme Cowan, Jiangtao Ma, Tim J Mitchell

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens.
LanguageEnglish
Pages3231-3237
Number of pages7
JournalVaccine
Volume28
Issue number18
DOIs
Publication statusPublished - 19 Apr 2010

Fingerprint

Genetic Conjugation
genetic conjugation
Streptococcus pneumoniae
Vaccines
vaccines
antigens
conjugated proteins
vaccination
Antigens
Vaccination
Proteins
proteins
green fluorescent protein
humoral immunity
Mucosal Immunity
adjuvants
Poisons
immunity
Green Fluorescent Proteins
immune response

Keywords

  • adhesins, bacterial
  • adjuvants, immunologic
  • animals
  • antibodies
  • bacterial proteins
  • female
  • green fluorescent proteins
  • humans
  • immunity, mucosal
  • immunoglobulin A
  • immunoglobulin G
  • lipoproteins
  • mice
  • mice, inbred BALB C
  • proteins
  • recombinant fusion proteins
  • sequence deletion
  • streptolysins
  • vaccines
  • synthetic vaccines

Cite this

Douce, Gill ; Ross, Kirsty ; Cowan, Graeme ; Ma, Jiangtao ; Mitchell, Tim J. / Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae. In: Vaccine. 2010 ; Vol. 28, No. 18. pp. 3231-3237.
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abstract = "Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens.",
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Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae. / Douce, Gill; Ross, Kirsty; Cowan, Graeme; Ma, Jiangtao; Mitchell, Tim J.

In: Vaccine, Vol. 28, No. 18, 19.04.2010, p. 3231-3237.

Research output: Contribution to journalArticle

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N2 - Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens.

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