In vivo screen of genetically conserved Streptococcus pneumoniae proteins for protective immunogenicity
Highlights • Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model. • Proteins were selected based on genetic conservation and surface accessibility to antibody. • Anti-sera used to investigate antigen expression across multiple serotypes. • Seven protective antigens w...
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| Published in | Vaccine Vol. 34; no. 50; pp. 6292 - 6300 |
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| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
07.12.2016
Elsevier Limited |
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| Abstract | Highlights • Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model. • Proteins were selected based on genetic conservation and surface accessibility to antibody. • Anti-sera used to investigate antigen expression across multiple serotypes. • Seven protective antigens were evaluated in additional animal models. • Protective antigens were Histidine triad’s or proteins bearing LPXTG linkage domains. |
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| AbstractList | We evaluated 52 differentE. coliexpressed pneumococcal proteins as immunogens in a BALB/c mouse model ofS. pneumoniaelung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA. We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA. Highlights • Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model. • Proteins were selected based on genetic conservation and surface accessibility to antibody. • Anti-sera used to investigate antigen expression across multiple serotypes. • Seven protective antigens were evaluated in additional animal models. • Protective antigens were Histidine triad’s or proteins bearing LPXTG linkage domains. •Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model.•Proteins were selected based on genetic conservation and surface accessibility to antibody.•Anti-sera used to investigate antigen expression across multiple serotypes.•Seven protective antigens were evaluated in additional animal models.•Protective antigens were Histidine triad’s or proteins bearing LPXTG linkage domains. We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected based on genetic conservation across disease-causing serotypes and bioinformatic prediction of antibody binding to the target antigen. Seven proteins induced protective responses, in terms of reduced lung burdens of the serotype 3 pneumococci. Three of the protective proteins were histidine triad protein family members (PhtB, PhtD and PhtE). Four other proteins, all bearing LPXTG linkage domains, also had activity in this model (PrtA, NanA, PavB and Eng). PrtA, NanA and Eng were also protective in a CBA/N mouse model of lethal pneumococcal infection. Despite data inferring widespread genomic conservation, flow-cytometer based antisera binding studies confirmed variable levels of antigen expression across a panel of pneumococcal serotypes. Finally, BALB/c mice were immunized and intranasally challenged with a viulent serotype 8 strain, to help understand the breadth of protection. Those mouse studies reaffirmed the effectiveness of the histidine triad protein grouping and a single LPXTG protein, PrtA. |
| Author | Guru, Siradanahalli Merson, James R Goenaga, Anne-Laure Weeratna, Risini Makinen, Shawn Lang, Susanne Falconer, Derek J Chang, Bingsheng Sheppard, Neil C Gracheck, Stephen J Green, Bruce A Eyles, Jim E Anderson, Richard J |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27816374$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1128_microbiolspec_GPP3_0028_2018 crossref_primary_10_1016_j_vaccine_2018_12_021 crossref_primary_10_1007_s10096_023_04560_6 crossref_primary_10_1159_000516956 crossref_primary_10_1089_vim_2017_0138 crossref_primary_10_1099_jmm_0_000724 crossref_primary_10_1080_21505594_2020_1825908 crossref_primary_10_3389_fcimb_2021_726740 crossref_primary_10_3390_pathogens9121014 crossref_primary_10_1111_imcb_12257 |
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| Snippet | Highlights • Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model. • Proteins were selected based on genetic conservation and... •Immunizing efficacy of 52 pneumococcal proteins evaluated in a mouse challenge model.•Proteins were selected based on genetic conservation and surface... We evaluated 52 different E. coli expressed pneumococcal proteins as immunogens in a BALB/c mouse model of S. pneumoniae lung infection. Proteins were selected... We evaluated 52 differentE. coliexpressed pneumococcal proteins as immunogens in a BALB/c mouse model ofS. pneumoniaelung infection. Proteins were selected... |
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| SubjectTerms | Allergy and Immunology Animals Antibody Antigen Antigens Antigens, Bacterial - genetics Antigens, Bacterial - immunology Bacteria Bacterial Load Bacterial Proteins - genetics Bacterial Proteins - immunology Cloning Cloning, Molecular Computational Biology Conserved Sequence Disease Models, Animal Escherichia coli Escherichia coli - genetics Experiments Female Gene Expression Genetic Testing Immunity Immunization Immunogenicity Laboratory animals Lipoproteins Lung - microbiology Mice, Inbred BALB C Mice, Inbred CBA Pneumococcal Pneumococcus Pneumonia Pneumonia, Pneumococcal - microbiology Pneumonia, Pneumococcal - prevention & control Proteins Streptococcus infections Streptococcus pneumoniae Streptococcus pneumoniae - genetics Streptococcus pneumoniae - immunology Survival Analysis Vaccine Vaccines |
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| Title | In vivo screen of genetically conserved Streptococcus pneumoniae proteins for protective immunogenicity |
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