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

2022 ◽  
Vol 67 (4) ◽  
pp. 289-298
Author(s):  
Saad Alghamdi ◽  
Muhammad Umar Khayam Sahibzada ◽  
Nashwa T. Shesha ◽  
Akhmed Aslam ◽  
Ahmed Kabrah ◽  
...  

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.

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 ◽  
...  

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.


2008 ◽  
Vol 57 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Michelle Darrieux ◽  
Adriana T. Moreno ◽  
Daniela M. Ferreira ◽  
Fabiana C. Pimenta ◽  
Ana Lúcia S. S. de Andrade ◽  
...  

Pneumococcal surface protein A (PspA) is an important vaccine candidate against pneumococcal infections, capable of inducing protection in different animal models. Based on its structural diversity, it has been suggested that a PspA-based vaccine should contain at least one fragment from each of the two major families (family 1, comprising clades 1 and 2, and family 2, comprising clades 3, 4 and 5) in order to elicit broad protection. This study analysed the recognition of a panel of 35 pneumococcal isolates bearing different PspAs by antisera raised against the N-terminal regions of PspA clades 1 to 5. The antiserum to PspA clade 4 was found to show the broadest cross-reactivity, being able to recognize pneumococcal strains containing PspAs of all clades in both families. The cross-reactivity of antibodies elicited against a PspA hybrid including the N-terminal region of clade 1 fused to a shorter and more divergent fragment (clade-defining region, or CDR) of clade 4 (PspA1–4) was also tested, and revealed a strong recognition of isolates containing clades 1, 4 and 5, and weaker reactions with clades 2 and 3. The analysis of serum reactivity against different PspA regions further revealed that the complete N-terminal region rather than just the CDR should be included in an anti-pneumococcal vaccine. A PspA-based vaccine is thus proposed to be composed of the whole N-terminal region of clades 1 and 4, which could also be expressed as a hybrid protein.


PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e27102 ◽  
Author(s):  
Masamitsu Kono ◽  
Muneki Hotomi ◽  
Susan K. Hollingshead ◽  
David E. Briles ◽  
Noboru Yamanaka

Vaccine ◽  
2013 ◽  
Vol 31 (20) ◽  
pp. 2465-2470 ◽  
Author(s):  
Fernanda A. Lima ◽  
Eliane N. Miyaji ◽  
Wagner Quintilio ◽  
Isaias Raw ◽  
Paulo L. Ho ◽  
...  

Author(s):  
Bin Chang ◽  
Yuki Kinjo ◽  
Masatomo Morita ◽  
Kosuke Tamura ◽  
Hiroshi Watanabe ◽  
...  

Pneumococcal surface protein A (PspA) is a surface protein of Streptococcus pneumoniae that may be a candidate antigen for new pneumococcal vaccines. This study investigates the distribution of PspA clades of the causative strains of adult invasive pneumococcal disease (IPD) in Japan. Of the 1,939 strains isolated from cases of adult IPD during 2014–2019, the PspA clades of 1,932 (99.6%) strains were determined, and no pspA was detected in the remaining 7 strains (0.4%). PspA clades 1–6 were detected in 786 (40.5%), 291 (15.0%), 443 (22.8%), 369 (19.0%), 33 (1.7%), and 6 (0.3%) strains, respectively. New PspA clades (0.2%) were identified in two non-typeable and two serotype 35B pneumococci. The proportions of clade 1 and clade 2 showed significantly decreased and increased trends, respectively. Furthermore, the PspA clade of pneumococcal strains was partially serotype- and sequence type-dependent. The majority of strains belonging to serotypes contained in both the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) belonged to PspA clades 1 or 3. In contrast, the distribution of clades in non-vaccine serotypes was wider than that of vaccine serotype pneumococci. Our findings demonstrate that almost all pneumococcal strains from adult IPD express PspA clades 1–4, especially for non-vaccine serotypes. These results may be useful for the development of a new pneumococcal vaccine with PspA.


Vaccine ◽  
2001 ◽  
Vol 20 (5-6) ◽  
pp. 805-812 ◽  
Author(s):  
Eliane N. Miyaji ◽  
Waldely O. Dias ◽  
Márcia Gamberini ◽  
Vera C.B.C. Gebara ◽  
Rocilda P.F. Schenkman ◽  
...  

2014 ◽  
Vol 10 (3) ◽  
pp. 1619-1625 ◽  
Author(s):  
SHANGYUN YING ◽  
JUN HE ◽  
MINJUN YU ◽  
YUKUAI ZHANG ◽  
SUHONG DENG ◽  
...  

1998 ◽  
Vol 11 (4) ◽  
pp. 645-657 ◽  
Author(s):  
David E. Briles ◽  
Rebecca Creech Tart ◽  
Edwin Swiatlo ◽  
Joseph P. Dillard ◽  
Patricia Smith ◽  
...  

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.


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