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Relative roles of genetic background and variation in PspA in the ability of antibodies to PspA to protect against capsular type 3 and 4 strains of Streptococcus pneumoniae

Roche, Hazeline; Ren, Bing; McDaniel, Larry S; Håkansson, Anders P LU and Briles, David E (2003) In Infection and Immunity 71(8). p.4498-4505
Abstract

Pneumococcal surface protein A (PspA) is able to elicit antibodies in mice and humans that can protect mice against fatal infection with Streptococcus pneumoniae. It has been observed that immunization with a single family 1 PspA can protect mice against infections with capsular type 3 or 6B strains expressing PspA family 1 or 2. However, several studies have shown that immunity to PspA is less efficacious against several capsular type 4 strains than against strains of capsular types 3, 6A, and 6B. To determine whether the greater difficulty in protecting against capsular type 4 strains resulted from differences in their PspAs or from differences in their genetic backgrounds, we performed protection experiments using four different... (More)

Pneumococcal surface protein A (PspA) is able to elicit antibodies in mice and humans that can protect mice against fatal infection with Streptococcus pneumoniae. It has been observed that immunization with a single family 1 PspA can protect mice against infections with capsular type 3 or 6B strains expressing PspA family 1 or 2. However, several studies have shown that immunity to PspA is less efficacious against several capsular type 4 strains than against strains of capsular types 3, 6A, and 6B. To determine whether the greater difficulty in protecting against capsular type 4 strains resulted from differences in their PspAs or from differences in their genetic backgrounds, we performed protection experiments using four different challenge strains: a capsular type 3 strain expressing a family 1 PspA (WU2), a capsular type 4 strain expressing a family 2 PspA (TIGR4), and genetically engineered variants of WU2 and TIGR4 expressing each other's PspAs. Prior to infection, the mice were immunized with recombinant family 1 or family 2 PspA. The results revealed that much of the difficulty in protecting against capsular type 4 strains was eliminated when mice were immunized with a homologous PspA of the same PspA family. However, regardless of which PspA the strains expressed, those on the TIGR4 background were about twice as hard to protect against as WU2 strains expressing the same PspA based on the efficacy rates seen in our experiments. These results point out the importance of including more than one PspA in any PspA vaccines developed for human use.

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author
publishing date
type
Contribution to journal
publication status
published
keywords
Animals, Antibodies, Bacterial, Antigens, Bacterial, Bacterial Proteins, Genetic Variation, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Pneumococcal Infections, Pneumococcal Vaccines, Species Specificity, Streptococcus pneumoniae
in
Infection and Immunity
volume
71
issue
8
pages
8 pages
publisher
American Society for Microbiology
external identifiers
  • Scopus:0042265132
ISSN
0019-9567
DOI
10.1128/IAI.71.8.4498-4505.2003
language
English
LU publication?
no
id
494b4f99-9ee4-4287-a542-858f0345cc6c
date added to LUP
2016-05-21 11:51:41
date last changed
2016-10-26 12:20:38
@misc{494b4f99-9ee4-4287-a542-858f0345cc6c,
  abstract     = {<p>Pneumococcal surface protein A (PspA) is able to elicit antibodies in mice and humans that can protect mice against fatal infection with Streptococcus pneumoniae. It has been observed that immunization with a single family 1 PspA can protect mice against infections with capsular type 3 or 6B strains expressing PspA family 1 or 2. However, several studies have shown that immunity to PspA is less efficacious against several capsular type 4 strains than against strains of capsular types 3, 6A, and 6B. To determine whether the greater difficulty in protecting against capsular type 4 strains resulted from differences in their PspAs or from differences in their genetic backgrounds, we performed protection experiments using four different challenge strains: a capsular type 3 strain expressing a family 1 PspA (WU2), a capsular type 4 strain expressing a family 2 PspA (TIGR4), and genetically engineered variants of WU2 and TIGR4 expressing each other's PspAs. Prior to infection, the mice were immunized with recombinant family 1 or family 2 PspA. The results revealed that much of the difficulty in protecting against capsular type 4 strains was eliminated when mice were immunized with a homologous PspA of the same PspA family. However, regardless of which PspA the strains expressed, those on the TIGR4 background were about twice as hard to protect against as WU2 strains expressing the same PspA based on the efficacy rates seen in our experiments. These results point out the importance of including more than one PspA in any PspA vaccines developed for human use.</p>},
  author       = {Roche, Hazeline and Ren, Bing and McDaniel, Larry S and Håkansson, Anders P and Briles, David E},
  issn         = {0019-9567},
  keyword      = {Animals,Antibodies, Bacterial,Antigens, Bacterial,Bacterial Proteins,Genetic Variation,Humans,Mice,Mice, Inbred BALB C,Mice, Inbred CBA,Pneumococcal Infections,Pneumococcal Vaccines,Species Specificity,Streptococcus pneumoniae},
  language     = {eng},
  number       = {8},
  pages        = {4498--4505},
  publisher    = {ARRAY(0xb7165a0)},
  series       = {Infection and Immunity},
  title        = {Relative roles of genetic background and variation in PspA in the ability of antibodies to PspA to protect against capsular type 3 and 4 strains of Streptococcus pneumoniae},
  url          = {http://dx.doi.org/10.1128/IAI.71.8.4498-4505.2003},
  volume       = {71},
  year         = {2003},
}