scholarly journals Evaluation of Pneumococcal Surface Protein A as a Vaccine Antigen against Secondary Streptococcus pneumoniae Challenge during Influenza A Infection

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 146
Author(s):  
Sean Roberts ◽  
Clare M. Williams ◽  
Sharon L. Salmon ◽  
Jesse L. Bonin ◽  
Dennis W. Metzger ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Protein A ◽  
Surface Protein ◽  
Vaccine Antigen ◽  
High Dose ◽  
Pneumococcal Surface Protein A ◽  
Relevant Dose

Secondary bacterial pneumonia is responsible for significant morbidity and mortality during seasonal and pandemic influenza. Due to the unpredictability of influenza A virus evolution and the time-consuming process of manufacturing strain-specific influenza vaccines, recent efforts have been focused on developing anti-Streptococcus pneumoniae immunity to prevent influenza-related illness and death. Bacterial vaccination to prevent viral-bacterial synergistic interaction during co-infection is a promising concept that needs further investigation. Here, we show that immunization with pneumococcal surface protein A (PspA) fully protects mice against low-dose, but not high-dose, secondary bacterial challenge using a murine model of influenza A virus-S. pneumoniae co-infection. We further show that immunization with PspA is more broadly protective than the pneumococcal conjugate vaccine (Prevnar). These results demonstrate that PspA is a promising vaccine target that can provide protection against a physiologically relevant dose of S. pneumoniae following influenza infection.

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.

scholarly journals Determination of phenotypes and pneumococcal surface protein A family types of Streptococcus pneumoniae from Malaysian healthy children

2013 ◽  
Vol 46 (3) ◽  
pp. 180-186 ◽  
Author(s):  
Masura Mohd Yatim ◽  
Siti Norbaya Masri ◽  
Mohd Nasir Mohd Desa ◽  
Niazlin Mohd Taib ◽  
Syafinaz Amin Nordin ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Healthy Children ◽  
Pneumococcal Surface Protein A ◽  
Family Types

Genetic diversity of pneumococcal surface protein A of Streptococcus pneumoniae meningitis in German children

Vaccine ◽  
2007 ◽  
Vol 25 (6) ◽  
pp. 1030-1035 ◽  
Author(s):  
Christiane Heeg ◽  
Carmen Franken ◽  
Mark van der Linden ◽  
Adnan Al-Lahham ◽  
Ralf René Reinert
Keyword(s):  
Genetic Diversity ◽  
Streptococcus Pneumoniae ◽  
Protein A ◽  
Surface Protein ◽  
Pneumococcal Surface Protein A ◽  
German Children

scholarly journals Contributions of Pneumolysin, Pneumococcal Surface Protein A (PspA), and PspC to Pathogenicity of Streptococcus pneumoniae D39 in a Mouse Model

2007 ◽  
Vol 75 (4) ◽  
pp. 1843-1851 ◽  
Author(s):  
Abiodun D. Ogunniyi ◽  
Kim S. LeMessurier ◽  
Rikki M. A. Graham ◽  
James M. Watt ◽  
David E. Briles ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Systemic Disease ◽  
Protein A ◽  
Virulence Gene ◽  
Surface Protein ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Virulence Proteins ◽  
Pneumococcal Surface Protein A ◽  
Genes Encoding

ABSTRACTSuccessful colonization of the upper respiratory tract byStreptococcus pneumoniaeis an essential first step in the pathogenesis of pneumococcal disease. However, the bacterial and host factors that provoke the progression from asymptomatic colonization to invasive disease are yet to be fully defined. In this study, we investigated the effects of single and combined mutations in genes encoding pneumolysin (Ply), pneumococcal surface protein A (PspA), and pneumococcal surface protein C (PspC, also known as choline-binding protein A) on the pathogenicity ofStreptococcus pneumoniaeserotype 2 (D39) in mice. Following intranasal challenge with D39, stable colonization of the nasopharynx was maintained over a 7-day period at a level of approximately 105bacteria per mouse. The abilities of the mutant deficient in PspA to colonize the nasopharynx and to cause lung infection and bacteremia were significantly reduced. Likewise, the PspC mutant and, to a lesser extent, the Ply mutant also had reduced abilities to colonize the nasopharynx. As expected, the double mutants colonized less well than the parent to various degrees and had difficulty translocating to the lungs and blood. A significant additive attenuation was observed for the double and triple mutants in pneumonia and systemic disease models. Surprisingly, the colonization profile of the derivative lacking all three proteins was similar to that of the wild type, indicating virulence gene compensation. These findings further demonstrate that the mechanism of pneumococcal pathogenesis is highly complex and multifactorial but ascribes a role for each of these virulence proteins, alone or in combination, in the process.

scholarly journals A Live Recombinant Avirulent Oral Salmonella Vaccine Expressing Pneumococcal Surface Protein A Induces Protective Responses against Streptococcus pneumoniae

1998 ◽  
Vol 66 (8) ◽  
pp. 3744-3751 ◽  
Author(s):  
Amiya R. Nayak ◽  
Steven A. Tinge ◽  
Rebecca C. Tart ◽  
Larry S. McDaniel ◽  
David E. Briles ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Vaccine Strain ◽  
Protein A ◽  
Surface Protein ◽  
Plasmid Vector ◽  
Oral Immunization ◽  
Diaminopimelic Acid ◽  
Host Chromosome ◽  
Pneumococcal Surface Protein A ◽  
Mucosal Antibody

ABSTRACT A live oral recombinant Salmonella vaccine strain expressing pneumococcal surface protein A (PspA) was developed. The strain was attenuated with Δcya Δcrp mutations. Stable expression of PspA was achieved by the use of the balanced-lethal vector-host system, which employs an asd deletion in the host chromosome to impose an obligate requirement for diaminopimelic acid. The chromosomal Δasd mutation was complemented by a plasmid vector possessing the asd + gene. A portion of the pspA gene from Streptococcus pneumoniae Rx1 was cloned onto a multicopy Asd+vector. After oral immunization, the recombinantSalmonella-PspA vaccine strain colonized the Peyer’s patches, spleens, and livers of BALB/cByJ and CBA/N mice and stimulated humoral and mucosal antibody responses. Oral immunization of outbred New Zealand White rabbits with the recombinant Salmonellastrain induced significant anti-PspA immunoglobulin G titers in serum and vaginal secretions. Polyclonal sera from orally immunized mice detected PspA on the S. pneumoniae cell surface as revealed by immunofluorescence. Oral immunization of BALB/cJ mice with the PspA-producing Salmonella strain elicited antibody to PspA and resistance to challenge by the mouse-virulent human clinical isolate S. pneumoniae WU2. Immune sera from orally immunized mice conferred passive protection against otherwise lethal intraperitoneal or intravascular challenge with strain WU2.

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