Characterization of Protective Immune Responses Induced by Pneumococcal Surface Protein A in Fusion with Pneumolysin Derivatives

ABSTRACT Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.

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Pneumococcal Surface Protein A does not affect the immune responses to a combined diphtheria tetanus and pertussis vaccine in mice

Vaccine ◽

10.1016/j.vaccine.2013.03.026 ◽

2013 ◽

Vol 31 (20) ◽

pp. 2465-2470 ◽

Cited By ~ 5

Author(s):

Fernanda A. Lima ◽

Eliane N. Miyaji ◽

Wagner Quintilio ◽

Isaias Raw ◽

Paulo L. Ho ◽

...

Keyword(s):

Immune Responses ◽

Pertussis Vaccine ◽

Protein A ◽

Surface Protein ◽

Pneumococcal Surface Protein A

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Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.4.32 ◽

2022 ◽

Vol 67 (4) ◽

pp. 289-298

Author(s):

Saad Alghamdi ◽

Muhammad Umar Khayam Sahibzada ◽

Nashwa T. Shesha ◽

Akhmed Aslam ◽

Ahmed Kabrah ◽

...

Keyword(s):

Immune Responses ◽

Pneumococcal Disease ◽

Vaccine Candidate ◽

Protein A ◽

Surface Protein ◽

Pneumococcal Infections ◽

Promising Candidate ◽

Host Immune Responses ◽

Pneumococcal Surface Protein A ◽

Potential Vaccine

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

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PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae

Vaccine ◽

10.1016/s0264-410x(01)00395-4 ◽

2001 ◽

Vol 20 (5-6) ◽

pp. 805-812 ◽

Cited By ~ 33

Author(s):

Eliane N. Miyaji ◽

Waldely O. Dias ◽

Márcia Gamberini ◽

Vera C.B.C. Gebara ◽

Rocilda P.F. Schenkman ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Immune Responses ◽

Dna Vaccines ◽

Protein A ◽

Surface Protein ◽

Cellular Immune Responses ◽

Pneumococcal Surface Protein A ◽

Cellular Immune

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Characterization of Binding of Human Lactoferrin to Pneumococcal Surface Protein A

Infection and Immunity ◽

10.1128/iai.69.5.3372-3381.2001 ◽

2001 ◽

Vol 69 (5) ◽

pp. 3372-3381 ◽

Cited By ~ 80

Author(s):

Anders Håkansson ◽

Hazeline Roche ◽

Shaper Mirza ◽

Larry S. McDaniel ◽

Alexis Brooks-Walter ◽

...

Keyword(s):

Amino Acids ◽

Protein A ◽

Surface Protein ◽

The Body ◽

Human Lactoferrin ◽

Bovine Lactoferrin ◽

Immune Functions ◽

Pneumococcal Surface Protein A ◽

Recombinant Fragments

ABSTRACT Human lactoferrin is an iron-binding glycoprotein that is particularly prominent in exocrine secretions and leukocytes and is also found in serum, especially during inflammation. It is able to sequester iron from microbes and has immunomodulatory functions, including inhibition of both complement activation and cytokine production. This study used mutants lacking pneumococcal surface protein A (PspA) and PspC to demonstrate that the binding of human lactoferrin to the surface of Streptococcus pneumoniae was entirely dependent on PspA. Lactoferrin bound both family 1 and family 2 PspAs. Binding of lactoferrin to PspA was shown by surface colocalization with PspA and was verified by the lack of binding to PspA-negative mutants. Lactoferrin was expressed on the body of the cells but was largely absent from the poles. PspC showed exactly the same distribution on the pneumococcal surface as PspA but did not bind lactoferrin. PspA's binding site for lactoferrin was mapped using recombinant fragments of PspA of families 1 and 2. Binding of human lactoferrin was detected primarily in the C-terminal half of the α-helical domain of PspA (amino acids 167 to 288 of PspA/Rx1), with no binding to the N-terminal 115 amino acids in either strain. The interaction was highly specific. As observed previously, bovine lactoferrin bound poorly to PspA. Human transferrin did not bind PspA at all. The binding of lactoferrin to S. pneumoniae might provide a way for the bacteria to interfere with host immune functions or to aid in the acquisition of iron at the site of infection.

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