Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

Colichio, Gabriela B. C.; Oliveira, Giuliana S.; Rodrigues, Tasson C.; Oliveira, Maria Leonor S.; Miyaji, Eliane N.

doi:10.3390/pathogens9040278

Cited by 9 publications

(4 citation statements)

References 39 publications

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“…A successful serotype-independent PspA-based vaccine against pneumococcus is a vaccine that comprises multiple immunological surface components with high cross-reactivity feature including various N-terminal domains of the PspA families [ 24 , 66 ]. So, the purpose of designing this study was first to improve the PspA-based vaccine potency and efficacy using immunoinformatics tools as the first line of vaccine design.…”

Section: Discussionmentioning

confidence: 99%

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

Afshari

Cohan

Sotoodehnejadnematalahi

et al. 2023

J Transl Med

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Background The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. Methods To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA1-5c+p vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA1-5c+p, we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA1-5c+p antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. Results For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA1-5c+p protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA1-5c+p IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. Conclusion Our findings elucidated the potential application of the PspA1-5c+p vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA1-5c+p vaccine candidate.

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Section: Discussionmentioning

confidence: 99%

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

Afshari

Cohan

Sotoodehnejadnematalahi

et al. 2023

J Transl Med

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“…Furthermore, purified protein-vaccine from the homologous family 2 cannot against infection caused by S. pneumoniae carrying family 1 [ 31 , 32 ]. Therefore, we considered that supplemental vaccine strategy that PCVs coupled with certain virulence factors maybe reduce the burden of pneumococcal disease based on the distribution of STs, serotypes and virulence factors [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular epidemiology of Streptococcus pneumoniae isolated from children with community-acquired pneumonia under 5 years in Chengdu, China

Chen

Liu

2022

Epidemiol. Infect.

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Streptococcus pneumoniae (S. pneumoniae) is one of the most common communityassociated pathogens responsible for pneumonia in children. This retrospective study aimed to investigate the molecular characteristics of S. pneumoniae isolated from children with community-acquired pneumonia (CAP) under 5 years in Chengdu, China. Molecular characteristics of S. pneumoniae included serotype and virulence factor performed by using PCR method and sequence types (STs) determined by sequencing seven housekeeping genes. In addition, the potential relationships between molecular characteristics were depicted by minimum spanning tree and correspondence analysis.The prevailing serotypes were 19F (18.52%), 6B (17.59%), 19A (13.89%), 6A (6.48%) and 23F (5.56%) among 108 isolates. The overall coverage rates of 7-valent, 10-valent, 13-valent, 15-valent, and 20-valent pneumococcal conjugate vaccines (PCVs) were 47.32%, 48.1%, 75%, 75%, and 78.7%, respectively. Meanwhile, the coverage rates of PCV13 among the isolates from CAP patients aged <1 year were high up to 84.2%.MLST analysis results showed that there were 56 different STs identified, of which the dominant STs were ST271 (22.22%) and ST320 (12.04%). 5 international clones among STs were observed, including Spain 23F -1, Spain 6B -2, Taiwan 19F -14, Netherlands 3 -31 and Denmark 14 -32. Additionally, most of the isolates carried ply, psaA, nanA, pavA, piaA, and CC271 isolates expressed more of nanA than non-CC271 isolates. Moreover, there were strong relevant relationships among STs, serotypes, and virulence factors.Considering serotypes and virulence factors together can be used as the foundation for the formulation of vaccine strategy.

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“…Furthermore, puri ed protein-vaccine from the homologous family 2 cannot against infection caused by S. pneumoniae carrying family 1 [32,33] . Therefore, we considered that supplemental vaccine strategy that PCVs coupled with certain virulence factors maybe reduce the burden of pneumococcal disease based on the distribution of STs, serotype and virulence factors [34] .…”

Section: Virulence Genes Distribution and Patternmentioning

confidence: 99%

Molecular epidemiology of Streptococcus Pneumoniae isolated from children with community-acquired pneumonia under 5 years in Chengdu, China

Liu

Chen

2022

Preprint

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Background: Streptococcus pneumoniae (S. Pneumoniae) is one of the most common community-associated pathogens responsible for pneumonia in children. This retrospective study aimed to investigate the molecular characteristics of S. Pneumoniae isolated from children with community-acquired pneumonia (CAP) under 5 years in Chengdu, China. Methods: Molecular characteristics of S. Pneumoniae included serotype and virulence factor performed by using PCR method and sequence types (STs) determined by sequencing seven housekeeping genes. In addition, the potential relationships between molecular characteristics were depicted by minimum spanning tree and correspondence analysis.Results: The prevailing serotypes were 19F (18.52%), 6B (17.59%), 19A (13.89%), 6A (6.48%) and 23F (5.56%) among 108 isolates. The overall coverage rates of 7-valent, 10-valent, 13-valent pneumococcal conjugate vaccines (PCVs) were 47.32%, 48.1%, 75%, respectively. Meanwhile, the coverage rates of PCV13 among the isolates from CAP patients aged <1 year were high up to 84.2%. MLST analysis results showed that there were 56 different STs identified, of which the dominant STs were ST271 (22.22%) and ST320 (12.04%). Additionally, most of the isolates carried ply, psaA, nanA, pavA, piaA, and CC271 isolates expressed more of nanA than non-CC271 isolates. Moreover, there were strong relevant relationships among STs, serotypes, virulence factors.Conclusion: Considering serotypes and virulence factors together can be used as the foundation for the formulation of vaccine strategy.

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Efficacy of a Protein Vaccine and a Conjugate Vaccine Against Co-Colonization with Vaccine-Type and Non-Vaccine Type Pneumococci in Mice

Cited by 9 publications

References 39 publications

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

In-silico design and evaluation of an epitope-based serotype-independent promising vaccine candidate for highly cross-reactive regions of pneumococcal surface protein A

Molecular epidemiology of Streptococcus pneumoniae isolated from children with community-acquired pneumonia under 5 years in Chengdu, China

Molecular epidemiology of Streptococcus Pneumoniae isolated from children with community-acquired pneumonia under 5 years in Chengdu, China

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