Clinical and Vaccine Immunology最新文献

{"title":"Effect of Breastfeeding and Additional Household Children on Cytomegalovirus Seroprevalence among U.S. Children 1 to 5 Years of Age.","authors":"Susanna Schmink, Deanna Kruszon-Moran, Sheila C Dollard, Tatiana M Lanzieri","doi":"10.1128/CVI.00243-17","DOIUrl":"https://doi.org/10.1128/CVI.00243-17","url":null,"abstract":"Congenital cytomegalovirus (CMV) infection may occur as a consequence of primary or nonprimary maternal infection during pregnancy (1). Postnatal CMV infection may develop in up to 40% of infants who are fed breast milk for 1 month by a CMV-seropositive mother (1). Further spread of CMV may result from child-to-child transmission in the household or day care center (2). In the 2011–2012 National Health and Nutrition Examination Survey (NHANES), overall CMV IgG seroprevalence among U.S. children 1 to 5 years of age was 21%, with a significant increase among those who were 5 years old (31%) compared to those who were 1 year old (12%) (3). CMV seroprevalence was significantly higher among nonHispanic black (25%) and Hispanic (31%) children than among non-Hispanic white children (11%) and among children living below versus at or above the poverty line (31% versus 15%) (3). Here, we describe additional results for the history of breastfeeding and number of household children 5 years old. NHANES, a nationally representative cross-sectional survey of the civilian noninstitutionalized U.S. population (4), included CMV antibody testing for 699 (62%) of the 1,135 children who were 1 to 5 years old examined in 2011 to 2012. To assess independent predictors of CMV IgG seroprevalence, we repeated the analysis as described in the previous report (3) and performed additional logistic-regression modeling on 636 children with complete data (out of the 682 children in the survey born in the 50 U.S. states and the District of Columbia). We performed all analyses using SUDAAN version 9.0 (Research Triangle Institute, Research Triangle Park, NC); results for which the P value was 0.05 were considered statistically significant. After adjusting for age, race/Hispanic origin, and poverty level, CMV IgG seroprevalence was significantly higher among children who were breastfed for 6 months (adjusted odds ratio [aOR] 3.1; 95% confidence interval [CI] 1.3 to 7.5), but not among children who were breastfed for up to 6 months (aOR 1.4; 95% CI 0.9 to 2.1), than among children who were not breastfed and among children living with 1 or more 5-year-old children in the household versus no other children (aOR 2.0; 95% CI 1.2 to 3.5). In the United States, demographic differences in CMV seroprevalence among children 1 to 5 years of age likely result from demographic differences in maternal CMV seroprevalence, breastfeeding, and child care practices. CMV seroprevalence is 90% among non-Hispanic black and Hispanic mothers and 53% among non-Hispanic white mothers (5); black mothers are the least likely to initiate and maintain breastfeeding compared to Hispanic and white mothers (6). In our study, the maternal CMV serostatus Citation Schmink S, Kruszon-Moran D, Dollard SC, Lanzieri TM. 2017. Effect of breastfeeding and additional household children on cytomegalovirus seroprevalence among U.S. children 1 to 5 years of age. Clin Vaccine Immunol 24:e00243-17. https://doi.org/10 .1128/CVI.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00243-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35228652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice.","authors":"Ahreum Kim,&nbsp;Yun-Gyoung Hur,&nbsp;Sunwha Gu,&nbsp;Sang-Nae Cho","doi":"10.1128/CVI.00219-17","DOIUrl":"https://doi.org/10.1128/CVI.00219-17","url":null,"abstract":"<p><p>The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of <i>Mycobacterium tuberculosis</i> in South Korea. Mice were immunized with MTKB_24820, <i>M. bovis</i> Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the <i>M. tuberculosis</i>-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (<i>P</i> < 0.05) and recalled gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-6, and IL-17 responses (<i>P</i> < 0.05 or <i>P</i> < 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log₁₀ reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4⁺ T cells producing protective cytokines, such as IFN-γ and IL-17, in lungs and spleens (<i>P</i> < 0.01) and CD4⁺ multifunctional T cells producing IFN-γ, tumor necrosis factor alpha (TNF-α), and/or IL-17 (<i>P</i> < 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-γ production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses <i>in vivo</i>, may be informative for vaccine development, particularly in regions where the <i>M. tuberculosis</i> Beijing/K-strain is frequently isolated from TB patients.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00219-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35379461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reevaluation of Positivity Cutoff Values for the Pneumococcal Urinary Antigen Detection Assay.","authors":"Michael W Pride,&nbsp;Kathrin U Jansen","doi":"10.1128/CVI.00239-17","DOIUrl":"https://doi.org/10.1128/CVI.00239-17","url":null,"abstract":"T o improve the clinical diagnosis of pneumococcal infection in bacteremic and nonbacteremic community-acquired pneumonia (CAP), a Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and validated. The UAD assay is a limit assay based on defined positivity cutoff limits and can simultaneously detect 13 different serotypes of Streptococcus pneumoniae by capturing serotype-specific S. pneumoniae polysaccharides (PnPSs) excreted in human urine. UAD assay validation and clinical validation of the corresponding positivity cutoff values were described in a previous publication in this journal (1). This assay was originally developed for use in the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) study (2) (adults (cid:2) 65 years of age). After the completion of sample testing in support of CAPiTA and study 6115A1-4007 (Distribu-tion of PCV 13 Serotype Streptococcus pneumoniae in Adults 50 Years and Older Presenting to Select U.S. Hospitals with Radiographically Confirmed Community-Acquired Pneumonia) (3), a critical component used in the UAD assay was received by an outside supplier and, as part of our laboratory’s standard practice, was qualified for use in the UAD assay, passing all prospectively set acceptance criteria. This new reagent was used in the UAD assay for a number of epidemiological studies to study the burden of the 13 serotypes covered by Prevnar 13 in subjects with community-acquired pneumonia. Upon review of the interim UAD results generated in support of the U.S. study 1147, it was noted that the percent positivity for serotype 5 was higher than expected for the U.S. population and higher","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00239-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35228651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients.","authors":"Eric K Dumas,&nbsp;Timothy Gross,&nbsp;Jason Larabee,&nbsp;Lance Pate,&nbsp;Hannah Cuthbertson,&nbsp;Sue Charlton,&nbsp;Bassam Hallis,&nbsp;Renata J M Engler,&nbsp;Limone C Collins,&nbsp;Christina E Spooner,&nbsp;Hua Chen,&nbsp;Jimmy Ballard,&nbsp;Judith A James,&nbsp;A Darise Farris","doi":"10.1128/CVI.00165-17","DOIUrl":"https://doi.org/10.1128/CVI.00165-17","url":null,"abstract":"<p><p>Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of <i>Bacillus anthracis</i> that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with <i>Bacillus anthracis</i> spores or ET. This study compared humoral responses to ET in recipients of AVP (<i>n</i> = 33) versus anthrax vaccine adsorbed (AVA; <i>n</i> = 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 ± 58.6) of EF antibodies than AVA (4.2% and 7.8 ± 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00165-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35379462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Reverse Vaccinology in the Design and Construction of Nanoglycoconjugate Vaccines against Burkholderia pseudomallei.","authors":"Laura A Muruato,&nbsp;Daniel Tapia,&nbsp;Christopher L Hatcher,&nbsp;Mridul Kalita,&nbsp;Paul J Brett,&nbsp;Anthony E Gregory,&nbsp;James E Samuel,&nbsp;Richard W Titball,&nbsp;Alfredo G Torres","doi":"10.1128/CVI.00206-17","DOIUrl":"https://doi.org/10.1128/CVI.00206-17","url":null,"abstract":"<p><p><i>Burkholderia pseudomallei</i> is a Gram-negative, facultative intracellular pathogen that causes the disease melioidosis in humans and other mammals. Respiratory infection with <i>B. pseudomallei</i> leads to a fulminant and often fatal disease. It has previously been shown that glycoconjugate vaccines can provide significant protection against lethal challenge; however, the limited number of known <i>Burkholderia</i> antigens has slowed progress toward vaccine development. The objective of this study was to identify novel antigens and evaluate their protective capacity when incorporated into a nanoglycoconjugate vaccine platform. First, an <i>in silico</i> approach to identify antigens with strong predicted immunogenicity was developed. Protein candidates were screened and ranked according to predicted subcellular localization, transmembrane domains, adhesive properties, and ability to interact with major histocompatibility complex (MHC) class I and class II. From these <i>in silico</i> predictions, we identified seven \"high priority\" proteins that demonstrated seroreactivity with anti-<i>B. pseudomallei</i> murine sera and convalescent human melioidosis sera, providing validation of our methods. Two novel proteins, together with Hcp1, were linked to lipopolysaccharide (LPS) and incorporated with the surface of a gold nanoparticle (AuNP). Animals receiving AuNP glycoconjugate vaccines generated high protein- and polysaccharide-specific antibody titers. Importantly, immunized animals receiving the AuNP-FlgL-LPS alone or as a combination demonstrated up to 100% survival and reduced lung colonization following a lethal challenge with <i>B. pseudomallei</i> Together, this study provides a rational approach to vaccine design that can be adapted for other complex pathogens and provides a rationale for further preclinical testing of AuNP glycoconjugate in animal models of infection.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00206-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35401717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Article of Significant Interest Selected from This Issue by the Editors","authors":"","doi":"10.1128/cvi.00272-17","DOIUrl":"https://doi.org/10.1128/cvi.00272-17","url":null,"abstract":"Effective Nanovaccines Protect against Lethal Burkholderia pseudomallei Infection Burkholderia pseudomallei, causative agent of melioidosis, exhibits high morbidity and mortality in humans. There are currently no vaccines available, and treatment options are limited. In the study by Muruato et al. (e00206-17), reverse vaccinology methods were used to identify novel, seroreactive Burkholderia antigens. Nanovaccines containing these proteins and Burkholderia lipopolysaccharide (LPS) generated high anti-protein and anti-LPS antibody titers in mice. One of these novel proteins, FlgL, provided 90% protection against lethal B. pseudomallei respiratory infection. Importantly, animals demonstrated a significant decrease in lung bacterial colonization compared to controls. These findings support further testing and development of nanovaccines against melioidosis.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72758807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equine Arteritis Virus Elicits a Mucosal Antibody Response in the Reproductive Tract of Persistently Infected Stallions.","authors":"Mariano Carossino,&nbsp;Bettina Wagner,&nbsp;Alan T Loynachan,&nbsp;R Frank Cook,&nbsp;Igor F Canisso,&nbsp;Lakshman Chelvarajan,&nbsp;Casey L Edwards,&nbsp;Bora Nam,&nbsp;John F Timoney,&nbsp;Peter J Timoney,&nbsp;Udeni B R Balasuriya","doi":"10.1128/CVI.00215-17","DOIUrl":"https://doi.org/10.1128/CVI.00215-17","url":null,"abstract":"<p><p>Equine arteritis virus (EAV) has the ability to establish persistent infection in the reproductive tract of the stallion (carrier) and is continuously shed in its semen. We have recently demonstrated that EAV persists within stromal cells and a subset of lymphocytes in the stallion accessory sex glands in the presence of a significant local inflammatory response. In the present study, we demonstrated that EAV elicits a mucosal antibody response in the reproductive tract during persistent infection with homing of plasma cells into accessory sex glands. The EAV-specific immunoglobulin isotypes in seminal plasma included IgA, IgG1, IgG3/5, and IgG4/7. Interestingly, seminal plasma IgG1 and IgG4/7 possessed virus-neutralizing activity, while seminal plasma IgA and IgG3/5 did not. However, virus-neutralizing IgG1 and IgG4/7 in seminal plasma were not effective in preventing viral infectivity. In addition, the serological response was primarily mediated by virus-specific IgM and IgG1, while virus-specific serum IgA, IgG3/5, IgG4/7, and IgG6 isotype responses were not detected. This is the first report characterizing the immunoglobulin isotypes in equine serum and seminal plasma in response to EAV infection. The findings presented herein suggest that while a broader immunoglobulin isotype diversity is elicited in seminal plasma, EAV has the ability to persist in the reproductive tract, in spite of local mucosal antibody and inflammatory responses. This study provides further evidence that EAV employs complex immune evasion mechanisms during persistence in the reproductive tract that warrant further investigation.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00215-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35417557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Terminal Pfs230 Domain Produced in Baculovirus as a Biological Active Transmission-Blocking Vaccine Candidate.","authors":"Shwu-Maan Lee,&nbsp;Chia-Kuei Wu,&nbsp;Jordan L Plieskatt,&nbsp;Kazutoyo Miura,&nbsp;John M Hickey,&nbsp;C Richter King","doi":"10.1128/CVI.00140-17","DOIUrl":"https://doi.org/10.1128/CVI.00140-17","url":null,"abstract":"<p><p>Transmission-blocking vaccines have the potential to accelerate malaria parasite elimination by inducing antibodies that block parasite transmission from humans to mosquitoes. Pfs230, a gametocyte surface protein involved in gamete function, has long been a promising candidate. Due to the large size (3,135 amino acids), complex domains, and repeating 6-cysteine (6-Cys) motifs with a multitude of disulfide bonds, the feasibility of expression of a full-length protein has been difficult. A priority focus, therefore, has been on the generation of single domains, including N-terminal fragments. Here we utilized a heterologous expression system, baculovirus, to produce an N-terminal domain of Pfs230 (Pfs230C1). Pfs230C1 (amino acids 443 to 731) with a polyhistidine affinity tag was expressed in Super Sf9 cells. Since the native host lacks glycosylation machinery, a single N585Q mutation was made to eliminate potential N-linked glycosylation. The expressed protein, purified by nickel affinity, ion exchange, and size exclusion chromatography to >90% purity, was present in monomeric form with an observed mass of 33,510 Da (matching oxidized form). Peptide mapping and disulfide analysis confirmed the proper formation of predicted disulfide bonds. Antibodies, generated against Pfs230C1 in mice, bound to the gametocyte in an immunofluorescence assay (IFA) and demonstrated functional activity in both the standard membrane feeding assay (SMFA) and the exflagellation assay (EXA). The biochemical, biophysical, and immunological results reported herein support the continued advancement of an N-terminal Pfs230 antigen (Pfs230C1) as a component of a transmission-blocking vaccine. Our results also support the continued use of the scalable baculovirus expression system for the generation of complex <i>Plasmodium</i> proteins.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00140-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35202656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlamydia trachomatis: the Persistent Pathogen.","authors":"Steven S Witkin,&nbsp;Evelyn Minis,&nbsp;Aikaterini Athanasiou,&nbsp;Julie Leizer,&nbsp;Iara M Linhares","doi":"10.1128/CVI.00203-17","DOIUrl":"https://doi.org/10.1128/CVI.00203-17","url":null,"abstract":"<p><p><i>Chlamydia trachomatis</i> is an obligate intracellular bacterium whose only natural host is humans. Although presenting as asymptomatic in most women, genital tract chlamydial infections are a leading cause of pelvic inflammatory disease, tubal factor infertility, and ectopic pregnancy. <i>C. trachomatis</i> has evolved successful mechanisms to avoid destruction by autophagy and the host immune system and persist within host epithelial cells. The intracellular form of this organism, the reticulate body, can enter into a persistent nonreplicative but viable state under unfavorable conditions. The infectious form of the organism, the elementary body, is again generated when the immune attack subsides. In its persistent form, <i>C. trachomatis</i> ceases to produce its major structural and membrane components, but synthesis of its 60-kDa heat shock protein (hsp60) is greatly upregulated and released from the cell. The immune response to hsp60, perhaps exacerbated by repeated cycles of productive infection and persistence, may promote damage to fallopian tube epithelial cells, scar formation, and tubal occlusion. The chlamydial and human hsp60 proteins are very similar, and hsp60 is one of the first proteins produced by newly formed embryos. Thus, the development of immunity to epitopes in the chlamydial hsp60 that are also present in the corresponding human hsp60 may increase susceptibility to pregnancy failure in infected women. Delineation of host factors that increase the likelihood that <i>C. trachomatis</i> will avoid immune destruction and survive within host epithelial cells and utilization of this knowledge to design individualized preventative and treatment protocols are needed to more effectively combat infections by this persistent pathogen.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00203-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35294313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis.","authors":"Cibelly Goulart,&nbsp;Dunia Rodriguez,&nbsp;Alex I Kanno,&nbsp;Thiago Rojas Converso,&nbsp;Ying-Jie Lu,&nbsp;Richard Malley,&nbsp;Luciana C C Leite","doi":"10.1128/CVI.00133-17","DOIUrl":"https://doi.org/10.1128/CVI.00133-17","url":null,"abstract":"<p><p>Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally, such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by interleukin-17A [IL-17A]) and invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed but poses potential safety and practical concerns in children. We have previously constructed a recombinant <i>Mycobacterium bovis</i> BCG strain expressing a pneumococcal surface protein A (PspA)-PdT fusion protein (rBCG PspA-PdT) that was able to induce an effective immune response and protection against sepsis in a prime-boost strategy. Here, we constructed two new rBCG strains expressing the pneumococcal proteins SP 0148 and SP 2108, which confer IL-17A-dependent protection against pneumococcal colonization in mouse models. Immunization of mice with rBCG 0148 or rBCG 2108 in a prime-boost strategy induced IL-17A and gamma interferon (IFN-γ) production. The combination of these rBCG strains with rBCG PspA-PdT (rBCG Mix), followed by a booster dose of the combined recombinant proteins (rMix) induced an IL-17A response against SP 0148 and SP 2108 and a humoral response characterized by increased levels of IgG2c against PspA and functional antibodies against pneumolysin. Furthermore, immunization with the rBCG Mix prime/rMix booster (rBCG Mix/rMix) provides protection against pneumococcal colonization and sepsis. These results suggest the use of combined rBCG strains as a potentially serotype-transcending pneumococcal vaccine in a prime-boost strategy, which could provide protection against pneumococcal colonization and sepsis.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00133-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35374967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}