Immunization with pneumococcal neuraminidases NanA, NanB and NanC to generate neutralizing antibodies and to increase survival in mice

Chiu, Cheng-Hsun; Chen, Chyi‐Liang; Hsu, Mei‐Hua; Liao, Wan-Chun; Chiu, Cheng-Hsun

doi:10.1099/jmm.0.000724

Cited by 10 publications

(4 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A combination of intact or truncated LytA, CbpJ, NanA, and BgaA may be attractive antigen candidates for the development of a universal pneumococcal vaccine. Several groups have already reported that individually, NanA and LytA work as protective antigens in mouse infection models (Berry et al, 1989;Lock et al, 1992;Long et al, 2004;Tong et al, 2005;Yuan et al, 2011;Janapatla et al, 2018). On the other hand, as non-pathogenic native microflora and other S. mitis group species also contain some of these genes, it is necessary to examine the possibility that the vaccine may alter the composition of oral and/or lung microbiomes.…”

Section: Discussionmentioning

confidence: 99%

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

et al. 2020

View full text Add to dashboard Cite

Streptococcus pneumoniae is a major cause of pneumonia, sepsis, and meningitis. Previously, we identified a novel virulence factor by investigating evolutionary selective pressure exerted on pneumococcal choline-binding cell surface proteins. Herein, we focus on another pneumococcal cell surface protein. Cell wall-anchoring proteins containing the LPXTG motif are conserved in Gram-positive bacteria. Our evolutionary analysis showed that among the examined genes, nanA and bgaA had high proportions of codon that were under significant negative selection. Both nanA and bgaA encode a multi-functional glycosidase that aids nutrient acquisition in a glucose-poor environment, pneumococcal adherence to host cells, and evasion from host immunity. However, several studies have shown that the role of BgaA is limited in a mouse pneumonia model, and it remains unclear if BgaA affects pneumococcal pathogenesis in a mouse sepsis model. To evaluate the distribution and pathogenicity of bgaA, we performed phylogenetic analysis and intravenous infection assay. In both Bayesian and maximum likelihood phylogenetic trees, the genetic distances between pneumococcal bgaA was small, and the cluster of pneumococcal bgaA did not contain other bacterial orthologs except for a Streptococcus gwangjuense gene. Evolutionary analysis and BgaA structure indicated BgaA active site was not allowed to change. The mouse infection assay showed that the deletion of bgaA significantly reduced host mortality. These results indicated that both nanA and bgaA encode evolutionally conserved pneumococcal virulence factors and that molecular evolutionary analysis could be a useful alternative strategy for identification of virulence factors.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Virulence genes are crucial candidate targets for the development of next-generation protein vaccines. For instance, a study reported that generate neutralizing antibodies immunization with pneumococcal neuraminidases nanA, nanB , and nanC was able to increase survival in mice (Janapatla et al, 2018). Our results showed that there is a high prevalence in nanA, piaA, lytA, ply, psaA, pavA, spxB, htrA and clpP whereas lower in cps2A, cbpA , and pspA .…”

Section: Discussionmentioning

confidence: 99%

Epidemiology Characteristics of Streptococcus pneumoniae From Children With Pneumonia in Shanghai: A Retrospective Study

Zhao

Pan

Wang

et al. 2019

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Background: Streptococcus pneumoniae is the most common pathogen causing death in children under 5 years old. This retrospective surveillance aimed to analyze serotype distribution, drug resistance, virulence factors, and molecular characteristics of pneumonia isolates from children in Shanghai, China. Methods: A total of 287 clinical pneumococcal isolates were collected from January to December in 2018 and were divided into community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HAP) two groups according to where someone contracts the infection. All isolates were serotyped by multiplex sequential PCR and antimicrobial susceptibility testing was performed using E-test or disk diffusion method. The molecular epidemiology was analyzed using multilocus sequence typing and seven housekeeping genes were sequenced to identified the sequence types (STs). In addition, we investigated the presence of virulence genes via PCR. Results: The most common serotypes were 19F, 6A, 19A, 23F, 14, and 6B, and the coverage rates of the 7-, 10- and 13-valent pneumococcal conjugate vaccines were 58.9, 58.9, and 80.5%, respectively. More PCV13/non-PCV7 serotypes and higher rate of penicillin non-susceptible S. pneumoniae were seen in HAP. Molecular epidemiological typing showed a high level of diversity and five international antibiotic-resistant clones were found, including Taiwan 19F -14, Spain 23F -1, Spain 6B -2, Taiwan 23F -15 and Sweden 15A -25. No significant difference was observed in the presence of virulence genes among the isolates obtained from CAP and HAP. All of the S. pneumoniae isolates carried lytA, ply, psaA, pavA, spxB, htrA , and clpP , and the carriage rate of nanA and piaA were 96.2 and 99.0%. Conversely, cps2A, cbpA , and pspA were present in 33.8–44.3% of the isolates. Conclusions: Serotype changes and emerging multidrug-resistant international clones were found in current study. lytA, ply, psaA, pavA, spxB, htrA , and clpP may be good protein vaccine candidates. Long-term high-quality surveillance should be conducted to assess impact and effectiveness brought by vaccines, and provide a foundation for prevention strategies and vaccine policies.

show abstract

“…Multiple pneumococcal proteins have been comparatively well investigated as promising targets for future non-serotype-specific protein-based pneumococcal vaccines, such as pneumococcal surface protein A (PspA) [17,18], pneumococcal surface protein C (PspC) [19,20], pneumococcal choline-binding protein (PcpA) [21], three neuraminidases (NanA, NanB, and NanC) [22,23], pneumolysin (Ply) [24], and four pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE) [25][26][27][28]. At present, an investigational pneumococcal vaccine is undergoing Phase I/II clinical trials in infants [29,30], children [31], and adults [32].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Various Vaccine Candidate Proteins in Clinical Isolates of Streptococcus pneumoniae: Characterization of the Novel Pht Fusion Proteins PhtA/B and PhtA/D

et al. 2019

View full text Add to dashboard Cite

Pneumococcal proteins unrelated to serotypes are considered to be candidates of antigens in next-generation vaccines. In the present study, the prevalence of vaccine candidate protein genes, along with serotypes and antimicrobial resistance determinants, was investigated in a total of 57 isolates obtained from a tertiary care hospital in Japan. All of the pediatric isolates and 76.6% of the adult isolates did not belong to PCV13 (a 13-valent pneumococcal conjugate vaccine) serotypes, and 70.2% of all isolates showed multidrug resistance. All of the isolates had ply, pavA, nanA, and nanB, and high prevalence was noted for the pspA and pspC genes (96.5% and 78.9%, respectively). Detection rates for the pneumococcal histidine triad protein (Pht) genes phtA, phtB, phtD, and phtE were 49.1%, 26.3%, 61.4%, and 100%, respectively. Two fusion-type genes, phtA/B and phtA/D, were identified, with a prevalence of 36.9% and 14.0%, respectively. These fusion types showed 78.1–90.0% nucleotide sequence identity with phtA, phtB, and phtD. The most prevalent pht profile was phtA + phtD + phtE (26.3%), followed by phtA/B + phtE (19.3%) and phtA/B + phtD + phtE (17.5%), while pht profiles including phtD and/or phtA/phtD were found in 71.9% of isolates. The present study revealed the presence of two fusion types of Pht and their unexpectedly high prevalence. These fusion types, as well as PhtA and PhtB, contained sequences similar to the B cell epitopes that have been previously reported for PhtD.

show abstract

Immunization with pneumococcal neuraminidases NanA, NanB and NanC to generate neutralizing antibodies and to increase survival in mice

Abstract: We recommend the inclusion of three pneumococcal neuraminidases in future protein vaccine formulations to prevent invasive pneumococcal infection caused by various serotypes.

Cited by 10 publications

References 77 publications

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

Role of BgaA as a Pneumococcal Virulence Factor Elucidated by Molecular Evolutionary Analysis

Epidemiology Characteristics of Streptococcus pneumoniae From Children With Pneumonia in Shanghai: A Retrospective Study

Prevalence of Various Vaccine Candidate Proteins in Clinical Isolates of Streptococcus pneumoniae: Characterization of the Novel Pht Fusion Proteins PhtA/B and PhtA/D

Contact Info

Product

Resources

About