scholarly journals Intranasal Immunization with Multivalent Group A Streptococcal Vaccines Protects Mice against Intranasal Challenge Infections

2004 ◽  
Vol 72 (5) ◽  
pp. 2507-2512 ◽  
Author(s):  
Mary A. Hall ◽  
Steven D. Stroop ◽  
Mary C. Hu ◽  
Michael A. Walls ◽  
Mark A. Reddish ◽  
...  

ABSTRACT We have previously shown that a hexavalent group A streptococcal M protein-based vaccine evoked bactericidal antibodies after intramuscular injection. In the present study, we show that the hexavalent vaccine formulated with several different mucosal adjuvants and delivered intranasally induced serum and salivary antibodies that protected mice from intranasal challenge infections with virulent group A streptococci. The hexavalent vaccine was formulated with liposomes with or without monophosphorylated lipid A (MPL), cholera toxin B subunit with or without holotoxin, or proteosomes from Neisseria meningitidis outer membrane proteins complexed with lipopolysaccharide from Shigella flexneri. Intranasal immunization with the hexavalent vaccine mixed with these adjuvants resulted in significant levels of antibodies in serum 2 weeks after the final dose. Mean serum antibody titers were equivalent in all groups of mice except those that were immunized with hexavalent protein plus liposomes without MPL, which were significantly lower. Salivary antibodies were also detected in mice that received the vaccine formulated with the four strongest adjuvants. T-cell proliferative assays and cytokine assays using lymphocytes from cervical lymph nodes and spleens from mice immunized with the hexavalent vaccine formulated with proteosomes indicated the presence of hexavalent protein-specific T cells and a Th1-weighted mixed Th1-Th2 cytokine profile. Intranasal immunization with adjuvanted formulations of the hexavalent vaccine resulted in significant levels of protection (80 to 100%) following intranasal challenge infections with type 24 group A streptococci. Our results indicate that intranasal delivery of adjuvanted multivalent M protein vaccines induces protective antibody responses and may provide an alternative to parenteral vaccine formulations.

Vaccine ◽  
2011 ◽  
Vol 29 (46) ◽  
pp. 8175-8178 ◽  
Author(s):  
James B. Dale ◽  
Thomas A. Penfound ◽  
Edna Y. Chiang ◽  
William J. Walton

2004 ◽  
Vol 132 (suppl. 1) ◽  
pp. 39-41 ◽  
Author(s):  
Branimir Nestorovic ◽  
Suzana Laban-Nestorovic ◽  
Veselinka Paripovic ◽  
Katarina Milosevic

Beta-hemolytic group A streptococcus (Streptococcus pyogenes) is the most common bacterial agent associated with the upper respiratory tract infections in humans. The most frequently group A streptococcus-associated disease is pharyngitis. Males and females are equally affected by group A streptococcus. There is seasonal increase in the prevalence of group A streptococcus-associated pharyngitis. Streptococcal pharyngitis is most prevalent in winter and early spring with higher incidence of disease observed in crowded population such as school children. Early diagnosis and treatment of group A streptococcal pharyngitis has been shown to reduce the severity of symptoms and further complications such as rheumatic fever and glomerulonephritis. The conventional methods used for identification of group A streptococci depend on isolation and identification of the organism on blood agar plates. These methods usually require 18-24 hours of incubation at 37?C. Such delay in identifying the group A streptococcus has often made physicians to administer therapy without first disclosing the etiological agent. Development of immunologic tests, capable of detecting the group A streptococcal antigen directly from the throat swabs, produced rapid test results employed for better treatment of patients. STREP A test is a rapid immunochromatographic test for the detection of group A streptococci from throat swabs or culture. The accuracy of the test does not depend on the organism viability. Instead, group A strep antigen is extracted directly from the swab and identified using antibodies specific for the group A carbohydrates. We compared rapid test with conventional throat swab in 40 children, who met Centor criteria for streptococcal pharyngitis (absence of cough, high fever, purulent pharyngitis, enlarged and painful cervical lymph nodes). Overall congruence of rapid test and culture was 94%. Test is easy to perform and it is recommended as the first diagnostic test for management of children with streptococcal pharyngitis. In children with negative test, but with characteristics highly suggestive of streptococcal infection, throat culture should be performed.


2003 ◽  
Vol 71 (9) ◽  
pp. 5097-5103 ◽  
Author(s):  
Harry S. Courtney ◽  
David L. Hasty ◽  
James B. Dale

ABSTRACT Serum opacity factor (SOF) is a protein expressed by Streptococcus pyogenes that opacifies mammalian serum. SOF is also a virulence factor of S. pyogenes, but it has not been previously shown to elicit a protective immune response. Herein, we report that SOF evokes bactericidal antibodies against S. pyogenes in humans, rabbits, and mice. Rabbit antiserum against purified recombinant SOF2 opsonized SOF-positive M type 2, 4, and 28 S. pyogenes in human blood but had no effect on SOF-negative M type 5 S. pyogenes. Furthermore, affinity-purified human antibodies against SOF2 also opsonized SOF-positive streptococci. A combination of antisera against M2 and SOF2 proteins was dramatically more effective in killing streptococci than either antiserum alone, indicating that antibodies against SOF2 enhance the opsonic efficiency of M protein antibodies. Mice tolerated an intravenous injection of 100 μg of SOF without overt signs of toxicity, and immunization with SOF protected mice against challenge infections with M type 2 S. pyogenes. These data indicate that SOF evokes opsonic antibodies that may protect against infections by SOF-positive serotypes of group A streptococci and suggest that different serotypes of SOF have common epitopes that may be useful vaccine candidates to protect against group A streptococcal infections.


2001 ◽  
Vol 293 (4) ◽  
pp. 165-170 ◽  
Author(s):  
Dean W. Brown ◽  
B. S. Baker ◽  
J.-M. Ovigne ◽  
Vincent A. Fischetti ◽  
Catherine Hardman ◽  
...  

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