Clinical and Vaccine Immunology最新文献

{"title":"The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma","authors":"S. Jordan, Kanupriya Gupta, Brian M O Ogendi, Rakesh K Bakshi, R. Kapil, C. G. Press, S. Sabbaj, Jeannette Y Lee, W. Geisler","doi":"10.1128/CVI.00010-17","DOIUrl":"https://doi.org/10.1128/CVI.00010-17","url":null,"abstract":"ABSTRACT Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86917072","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":"Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity","authors":"Katharina Richard, B. Mann, A. Qin, E. Barry, R. Ernst, S. Vogel","doi":"10.1128/CVI.00574-16","DOIUrl":"https://doi.org/10.1128/CVI.00574-16","url":null,"abstract":"ABSTRACT Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the United States. Previously, we showed that incorporating lysates from partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal (i.p.) challenge in mice. However, we achieved only partial protection against F. tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous prime-boost immunization strategies. We now extend these findings to show that both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers of anti-F. tularensis IgG and that the titers could be further increased by adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) adjuvant that is included in several U.S. FDA-approved vaccines. LVS-V+MPL immune sera also detected more F. tularensis antigens than LVS-V immune sera and, after passive transfer to naive mice, significantly delayed the time to death against F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active immunization with LVS-V+MPL (i.p./i.p.) also increased the frequency of gamma interferon (IFN-γ)-secreting activated helper T cells, IFN-γ production, and the ability of splenocytes to control intramacrophage F. tularensis LVS replication ex vivo. Active LVS-V+MPL immunization via heterologous routes (i.p./i.n.) significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and significantly enhanced protection against i.n. F. tularensis Schu S4 challenge (to ∼60%). These data represent a significant step in the development of a subunit vaccine against the highly virulent type A strains.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85311260","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":"Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.","authors":"Kara Jensen, Myra Grace Dela Pena-Ponce, Michael Piatak, Rebecca Shoemaker, Kelli Oswald, William R Jacobs, Glenn Fennelly, Carissa Lucero, Katie R Mollan, Michael G Hudgens, Angela Amedee, Pamela A Kozlowski, Jacob D Estes, Jeffrey D Lifson, Koen K A Van Rompay, Michelle Larsen, Kristina De Paris","doi":"10.1128/CVI.00360-16","DOIUrl":"10.1128/CVI.00360-16","url":null,"abstract":"<p><p>Our goal is to develop a pediatric combination vaccine to protect the vulnerable infant population against human immunodeficiency virus type 1 (HIV-1) and tuberculosis (TB) infections. The vaccine consists of an auxotroph Mycobacterium tuberculosis strain that coexpresses HIV antigens. Utilizing an infant rhesus macaque model, we have previously shown that this attenuated M. tuberculosis (AMtb)-simian immunodeficiency virus (SIV) vaccine is immunogenic, and although the vaccine did not prevent oral SIV infection, a subset of vaccinated animals was able to partially control virus replication. However, unexpectedly, vaccinated infants required fewer SIV exposures to become infected compared to naive controls. Considering that the current TB vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), can induce potent innate immune responses and confer pathogen-unspecific trained immunity, we hypothesized that an imbalance between enhanced myeloid cell function and immune activation might have influenced the outcome of oral SIV challenge in AMtb-SIV-vaccinated infants. To address this question, we used archived samples from unchallenged animals from our previous AMtb-SIV vaccine studies and vaccinated additional infant macaques with BCG or AMtb only. Our results show that vaccinated infants, regardless of vaccine strain or regimen, had enhanced myeloid cell responses. However, CD4⁺ T cells were concurrently activated, and the persistence of these activated target cells in oral and/or gastrointestinal tissues may have facilitated oral SIV infection. Immune activation was more pronounced in BCG-vaccinated infant macaques than in AMtb-vaccinated infant macaques, indicating a role for vaccine attenuation. These findings underline the importance of understanding the interplay of vaccine-induced immunity and immune activation and its effect on HIV acquisition risk and outcome in infants.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216431/pdf/e00360-16.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9857031","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":"Calibration and Evaluation of Quantitative Antibody Titers for Measles Virus by Using the BioPlex 2200.","authors":"Todd F Hatchette, Heidi Scholz, Shelly Bolotin, Natasha S Crowcroft, Colleen Jackson, Elizabeth McLachlan, Alberto Severini","doi":"10.1128/CVI.00269-16","DOIUrl":"10.1128/CVI.00269-16","url":null,"abstract":"<p><p>The BioPlex 2200 (Bio-Rad Laboratories, Hercules, CA) is a rapid, automated platform, which can screen large numbers of specimens for antibodies to measles, mumps, rubella, and varicella. Although approved for producing qualitative results, in this study we validated the test (off-label) to allow reporting of quantitative results. To do this, we used the third anti-measles World Health Organization standard to generate a calibration curve that allowed relative fluorescence intensity to be translated into quantitative antibody titer (antibody units [AU]/ml). The results from the BioPlex 2200 and the reference plaque reduction neutralization test (PRNT) exhibited a reasonable correlation following an exponential function, but correlation was poor in low-titer samples. Using a receiver operating characteristics analysis, an equivocal zone for the BioPlex 2200 was established between ≥0.13 and <1.10 AU/ml to achieve 100% specificity (95% confidence interval [CI] = 83.2 to 100%) and 100% sensitivity (95% CI = 93.5 to 100%) versus PRNT. By determining an equivocal range requiring confirmation by PRNT, we can avoid underestimating the levels of immunity through false-negative results and optimize methods for seroepidemiological studies.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00269-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75287714","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":"Multivalent and Multipathogen Viral Vector Vaccines.","authors":"Katharina B Lauer, Ray Borrow, Thomas J Blanchard","doi":"10.1128/CVI.00298-16","DOIUrl":"10.1128/CVI.00298-16","url":null,"abstract":"<p><p>The presentation and delivery of antigens are crucial for inducing immunity and, desirably, lifelong protection. Recombinant viral vectors-proven safe and successful in veterinary vaccine applications-are ideal shuttles to deliver foreign proteins to induce an immune response with protective antibody levels by mimicking natural infection. Some examples of viral vectors are adenoviruses, measles virus, or poxviruses. The required attributes to qualify as a vaccine vector are as follows: stable insertion of coding sequences into the genome, induction of a protective immune response, a proven safety record, and the potential for large-scale production. The need to develop new vaccines for infectious diseases, increase vaccine accessibility, reduce health costs, and simplify overloaded immunization schedules has driven the idea to combine antigens from the same or various pathogens. To protect effectively, some vaccines require multiple antigens of one pathogen or different pathogen serotypes/serogroups in combination (multivalent or polyvalent vaccines). Future multivalent vaccine candidates are likely to be required for complex diseases like malaria and HIV. Other novel strategies propose an antigen combination of different pathogens to protect against several diseases at once (multidisease or multipathogen vaccines).</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216423/pdf/e00298-16.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34317401","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":"Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries.","authors":"Katayi Mwila, Roma Chilengi, Michelo Simuyandi, Sallie R Permar, Sylvia Becker-Dreps","doi":"10.1128/CVI.00405-16","DOIUrl":"10.1128/CVI.00405-16","url":null,"abstract":"<p><p>The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low- and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74932832","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":"Articles of Significant Interest Selected from This Issue by the Editors","authors":"","doi":"10.1128/CVI.00535-16","DOIUrl":"https://doi.org/10.1128/CVI.00535-16","url":null,"abstract":"considerable interest in farming cyanobacteria for the production of commercial goods (e.g., biofuels), but scaled cultivation of these microbes is stymied by economic barriers to processing large liquid volumes containing small, tough cells. In a study by Jordan et al. (e00053-17), division machinery of cyanobacteria was tunably controlled to disentangle processes of growth from cell division. The authors show that cyanobacteria can be triggered to increase in size by (cid:2) 3 orders of magnitude, creating cells more amenable to harvest and lysis. As such, they show that genetic approaches can be used to engineer cyanobacteria that are more compatible with bioprocessing equipment, rather than vice versa. They found that was a key predictor of anti- B. dendrobatidis bacterial richness and prevalence. indicate that harbor diverse antifungal bacteria that vary across the and likely serve a protective","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73900248","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":"Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population","authors":"L. Trotz-Williams, N. Mercer, K. Paphitis, J. Walters, D. Wallace, E. Kristjanson, J. Gubbay, T. Mazzulli","doi":"10.1128/CVI.00542-16","DOIUrl":"https://doi.org/10.1128/CVI.00542-16","url":null,"abstract":"ABSTRACT In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74163748","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":"Serological Analysis of Tuberculosis in Goats by Use of the Enferplex Caprine TB Multiplex Test","authors":"Amanda O’Brien, Clare Whelan, J. Clarke, A. Hayton, N. Watt, G. Harkiss","doi":"10.1128/CVI.00518-16","DOIUrl":"https://doi.org/10.1128/CVI.00518-16","url":null,"abstract":"ABSTRACT Tuberculosis in goats is usually diagnosed clinically, at postmortem, or by a positive skin test. However, none of these approaches detects all infected animals. Serology offers an additional tool to identify infected animals missed by current tests. We describe the use of the Enferplex Caprine TB serology test to aid the management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in both serum and milk from 100% of skin test-positive animals and in serum and milk from 77.8 and 95.4% of skin test-negative animals, respectively. A good correlation was observed between serum and milk antibody levels. The herd had been vaccinated against Mycobacterium avium subsp. paratuberculosis, but no direct serological cross-reactions were found. Subsequent skin testing revealed 13.7% positive animals, 64.9% of which were antibody positive, while 42.1% of skin test-negative animals were seropositive. Antibody responses remained high 1 month later (57.1% positive), and the herd was slaughtered. Postmortem analysis of 20 skin test-negative goats revealed visible lesions in 6 animals, all of which had antibodies to six Mycobacterium bovis antigens. The results provide indirect evidence that serology testing with serum or milk could be a useful tool in the diagnosis and management of tuberculosis in goats.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88650358","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":"Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax.","authors":"Wilbur H Chen, Marcela F Pasetti, Rajan P Adhikari, Holly Baughman, Robin Douglas, Jill El-Khorazaty, Nancy Greenberg, Frederick W Holtsberg, Grant C Liao, Mardi K Reymann, Xiaolin Wang, Kelly L Warfield, M Javad Aman","doi":"10.1128/CVI.00399-16","DOIUrl":"10.1128/CVI.00399-16","url":null,"abstract":"<p><p>Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB) containing 3 distinct mutations in the major histocompatibility complex class II binding site was combined with an alum adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax. Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a first-in-human open-label dose escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg. Safety was assessed by determination of the frequency of adverse events and reactogenicity. Immune responses to the vaccination were determined by measurement of anti-staphylococcal enterotoxin B (anti-SEB) IgG by enzyme-linked immunosorbent assay and a toxin neutralization assay (TNA). Twenty-eight participants were enrolled in 7 dosing cohorts. All doses were well tolerated. The participants exhibited heterogeneous baseline antibody titers. More seroconversions and a faster onset of serum anti-SEB IgG toxin-neutralizing antibodies were observed by TNA with increasing doses of STEBVax. There was a trend for a plateau in antibody responses with doses of STEBVax of between 2.5 and 20 μg. Among the participants vaccinated with 2.5 μg to 20 μg of STEBVax, ∼93% seroconverted for SEB toxin-neutralizing antibody. A strong correlation between individual SEB-specific serum IgG antibody titers and the neutralization of gamma interferon production was found in vitro STEBvax appeared to be safe and immunogenic, inducing functional toxin-neutralizing antibodies. These data support its continued clinical development. (This study has been registered at ClinicalTrials.gov under registration no. NCT00974935.).</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5139602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78179859","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}