A12560 Dual vaccine based on angiotensin II type 1 receptor and pneumococcal surface protein A simultaneously induced therapeutically potent antibodies for the attenuation of hypertension and pneumococcal infection in rodents

2018 ◽  
Vol 36 ◽  
pp. e69
Author(s):  
Tatsuhiko Azegami ◽  
Kaori Hayashi ◽  
Akihito Hishikawa ◽  
Norifumi Yoshimoto ◽  
Hiroshi Itoh
Keyword(s):  
Angiotensin Ii ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Pneumococcal Surface Protein A

Intranasal vaccination against angiotensin II type 1 receptor and pneumococcal surface protein A attenuates hypertension and pneumococcal infection in rodents

2018 ◽  
Vol 36 (2) ◽  
pp. 387-394 ◽  
Author(s):  
Tatsuhiko Azegami ◽  
Yoshikazu Yuki ◽  
Kaori Hayashi ◽  
Akihito Hishikawa ◽  
Shin-ichi Sawada ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Pneumococcal Surface Protein A

scholarly journals Effects of Zinc Deficiency and Pneumococcal Surface Protein A Immunization on Zinc Status and the Risk of Severe Infection in Mice

2003 ◽  
Vol 71 (4) ◽  
pp. 2009-2013 ◽  
Author(s):  
Tor A. Strand ◽  
Susan K. Hollingshead ◽  
Kåre Julshamn ◽  
David E. Briles ◽  
Bjørn Blomberg ◽  
...  
Keyword(s):  
Zinc Deficiency ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Zinc Status ◽  
Pneumococcal Surface Protein A ◽  
Increased Risk ◽  
Zinc Depletion ◽  
Severe Infections ◽  
Tract Infections

ABSTRACT Streptococcus pneumoniae is a major cause of illness and death in children in developing countries. In these children, zinc deficiency is associated with an increased risk of acute respiratory tract infections, which can be reduced by daily zinc administration. Severe infections decrease zinc levels in plasma and may thereby move individuals with preexisting low zinc stores into a vicious cycle of infection and unavailable zinc. Pneumococcal surface protein A (PspA) has emerged as a promising vaccine candidate, and immunization with this antigen protects animals from pneumococcal infection. In an animal experiment, we measured the effect of zinc depletion on the immune response to parenterally administrated PspA and assessed the effect of this PspA vaccination and zinc depletion on the severity of pneumococcal infection and on zinc status. Mice were kept on different diets for 5 weeks, immunized twice 14 days apart, and challenged intranasally with S. pneumoniae. Mice on the zinc-deficient diet showed substantially reduced immune responses to PspA, more extensive pneumococcal colonization in the nasal mucosa, more severe infections, and an increased risk of death. PspA immunization reduced the risk of severe disease, and the reduction in severity was reflected in substantially reduced zinc depletion from bones.

scholarly journals Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)

1998 ◽  
Vol 11 (4) ◽  
pp. 645-657 ◽  
Author(s):  
David E. Briles ◽  
Rebecca Creech Tart ◽  
Edwin Swiatlo ◽  
Joseph P. Dillard ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Significant Risk ◽  
Surface Protein ◽  
Infectious Agent ◽  
The Elderly ◽  
Multidrug Resistant ◽  
Pneumococcal Surface Protein A ◽  
Potential Vaccine

SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.

scholarly journals Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191692 ◽  
Author(s):  
Tasson C. Rodrigues ◽  
Maria Leonor S. Oliveira ◽  
Alessandra Soares-Schanoski ◽  
Stefanni L. Chavez-Rico ◽  
Douglas B. Figueiredo ◽  
...  
Keyword(s):  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Mucosal Immunization ◽  
Pneumococcal Surface Protein A

scholarly journals Protective humoral response against pneumococcal infection in mice elicited by recombinant bacille Calmette-Guérin vaccines expressing pneumococcal surface protein A.

1994 ◽  
Vol 180 (6) ◽  
pp. 2277-2286 ◽  
Author(s):  
S Langermann ◽  
S R Palaszynski ◽  
J E Burlein ◽  
S Koenig ◽  
M S Hanson ◽  
...  
Keyword(s):  
Capsular Polysaccharide ◽  
Gene Segment ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Cross Protection ◽  
Secreted Protein ◽  
Bacille Calmette Guerin ◽  
Immunodeficient Mice ◽  
Pneumococcal Surface Protein A

Pneumococcal surface protein A (PspA), a cell-surface protein present on all strains of pneumococci, has been shown to elicit protective antibody responses in mice in the absence of capsular polysaccharide. Whereas PspA is polymorphic, considerable cross-reactivity and cross-protection have been demonstrated among PspA proteins of pneumococci exhibiting different capsular and PspA serotypes. A gene segment encoding the nonrepetitive variable NH2-terminal portion of PspA has been cloned into three distinct recombinant Bacille Calmette-Guérin (rBCG) vectors, allowing for expression of PspA as a cytoplasmic or secreted protein, or a chimeric exported membrane-associated lipoprotein. All rBCG-PspA strains elicited comparable anti-PspA ELISA titers, ranging from 10(4) to 10(5) (reciprocal titers) in both BALB/c and C3H/HeJ mice. However, protective responses were observed only in animals immunized with the rBCG-PspA vaccines expressing PspA as a secreted protein or chimeric exported lipoprotein. In addition, anti-PspA immune sera elicited by the rBCG vaccines passively protected X-linked immunodeficient mice from lethal challenge with the highly virulent, encapsulated WU2 strain of Streptococcus pneumoniae and two additional virulent strains exhibiting heterologous PspA and capsular serotypes. These studies confirm previous PspA immunization studies showing cross-protection against heterologous serotypes of S. pneumoniae and demonstrate a potential for rBCG-based PspA vaccines to elicit protective humoral responses against pneumococcal disease in humans.

scholarly journals DNA vaccines expressing pneumococcal surface protein A (PspA) elicit protection levels comparable to recombinant protein

2006 ◽  
Vol 55 (4) ◽  
pp. 375-378 ◽  
Author(s):  
Daniela M. Ferreira ◽  
Eliane N. Miyaji ◽  
Maria Leonor S. Oliveira ◽  
Michelle Darrieux ◽  
Ana Paula M. Arêas ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Recombinant Protein ◽  
Dna Vaccines ◽  
Protein A ◽  
Surface Protein ◽  
Humoral Response ◽  
Cost Effective ◽  
Promising Candidate ◽  
Pneumococcal Surface Protein A ◽  
Antibody Levels

Pneumococcal surface protein A (PspA) is a promising candidate for the development of cost-effective vaccines against Streptococcus pneumoniae. In the present study, BALB/c mice were immunized with DNA vaccine vectors expressing the N-terminal region of PspA. Animals immunized with a vector expressing secreted PspA developed higher levels of antibody than mice immunized with the vector expressing the antigen in the cytosol. However, both immunogens elicited similar levels of protection against intraperitoneal challenge. Furthermore, immunization with exactly the same fragment in the form of a recombinant protein, with aluminium hydroxide as an adjuvant, elicited even higher antibody levels, but this increased humoral response did not correlate with enhanced protection. These results show that DNA vaccines expressing PspA are able to elicit protection levels comparable to recombinant protein, even though total anti-PspA IgG response is considerably lower.

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