Nicholas H Carbonetti, Carl Heinz Wirsing von König, Ruiting Lan, Francoise Jacob-Dubuisson, Peggy A Cotter, Rajendar Deora, Tod J Merkel, Cécile A van Els, Camille Locht, Daniela Hozbor, Maria E Rodriguez
{"title":"Erratum for Carbonetti et al., \"Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development\".","authors":"Nicholas H Carbonetti, Carl Heinz Wirsing von König, Ruiting Lan, Francoise Jacob-Dubuisson, Peggy A Cotter, Rajendar Deora, Tod J Merkel, Cécile A van Els, Camille Locht, Daniela Hozbor, Maria E Rodriguez","doi":"10.1128/CVI.00071-17","DOIUrl":"https://doi.org/10.1128/CVI.00071-17","url":null,"abstract":"Nicholas H. Carbonetti, Carl Heinz Wirsing von König, Ruiting Lan, Francoise Jacob-Dubuisson, Peggy A. Cotter, Rajendar Deora, Tod J. Merkel, Cécile A. van Els, Camille Locht, Daniela Hozbor, Maria E. Rodriguez University of Maryland School of Medicine, Baltimore, Maryland, USA; Labor:Medizin Krefeld MVZ GmbH, Krefeld, Germany; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia; Institut Pasteur de Lille, Inserm U1019, CNRS UMR8204, University of Lille, Center for Infection and Immunity of Lille, Lille, France; University of North Carolina—Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA; Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, the Netherlands; IBBM, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina; CINDEFI (CONICET-UNLP), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00071-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34972104","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":"Exploring Human Antimicrobial Antibody Responses on a Single B Cell Level.","authors":"Daniel Hofmann, Jonathan R Lai","doi":"10.1128/CVI.00544-16","DOIUrl":"https://doi.org/10.1128/CVI.00544-16","url":null,"abstract":"<p><p>Analysis of monoclonal antibodies (MAbs) derived from single B cell cloning has been highly beneficial for antimicrobial immunotherapy, vaccine design, and advancing our understanding of pathogen-triggered effects on the human immunoglobulin repertoire. Sequencing of variable domains of single B cells, and characterization of binding and functional activities of MAbs derived from those sequences, provides in-depth insight not only into sites of susceptibility for antibody-mediated neutralization or opsonization of the pathogen but also into the dynamics of protective antibody evolution during infection. This information can be utilized to rapidly develop novel immunotherapies of completely human origin and provides a roadmap for structure-based vaccine design that aims to elicit similar protective antibody responses. Here, we summarize recent aspects of the single B cell cloning approach.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00544-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34868665","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}
Paula M Ladwig, David R Barnidge, Maria A V Willrich
{"title":"Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory.","authors":"Paula M Ladwig, David R Barnidge, Maria A V Willrich","doi":"10.1128/CVI.00545-16","DOIUrl":"https://doi.org/10.1128/CVI.00545-16","url":null,"abstract":"<p><p>Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00545-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34796095","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}
Qihua Fan, Cody S Nelson, Kristy M Bialas, Flavia Chiuppesi, Joshua Amos, Thaddeus C Gurley, Dawn Jones Marshall, Joshua Eudailey, Holly Heimsath, Jonathon Himes, Ashlesha Deshpande, Mark R Walter, Felix Wussow, Don J Diamond, Peter A Barry, M Anthony Moody, Amitinder Kaur, Sallie R Permar
{"title":"Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.","authors":"Qihua Fan, Cody S Nelson, Kristy M Bialas, Flavia Chiuppesi, Joshua Amos, Thaddeus C Gurley, Dawn Jones Marshall, Joshua Eudailey, Holly Heimsath, Jonathon Himes, Ashlesha Deshpande, Mark R Walter, Felix Wussow, Don J Diamond, Peter A Barry, M Anthony Moody, Amitinder Kaur, Sallie R Permar","doi":"10.1128/CVI.00510-16","DOIUrl":"https://doi.org/10.1128/CVI.00510-16","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4<sup>+</sup> T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4<sup>+</sup> T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMV-reactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00510-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34815898","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}
Sasirekha Ramani, Frederick H Neill, Jennifer Ferreira, John J Treanor, Sharon E Frey, David J Topham, Robert R Goodwin, Astrid Borkowski, Frank Baehner, Paul M Mendelman, Mary K Estes, Robert L Atmar
{"title":"B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine.","authors":"Sasirekha Ramani, Frederick H Neill, Jennifer Ferreira, John J Treanor, Sharon E Frey, David J Topham, Robert R Goodwin, Astrid Borkowski, Frank Baehner, Paul M Mendelman, Mary K Estes, Robert L Atmar","doi":"10.1128/CVI.00571-16","DOIUrl":"https://doi.org/10.1128/CVI.00571-16","url":null,"abstract":"ABSTRACT Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the first identified correlate of protection from HuNoV gastroenteritis. Recently, virus-specific IgG memory B cells were identified to be another potential correlate of protection against HuNoV gastroenteritis. We assessed B-cell responses following intramuscular administration of a bivalent (genogroup I, genotype 1 [GI.1]/genogroup II, genotype 4 [GII.4]) VLP vaccine using protocols identical to those used to evaluate cellular immunity following experimental GI.1 HuNoV infection. The kinetics and magnitude of cellular immunity to G1.1 infection were compared to those after VLP vaccination. Intramuscular immunization with the bivalent VLP vaccine induced the production of antibody-secreting cells (ASCs) and memory B cells. ASC responses peaked at day 7 after the first dose of vaccine and returned to nearly baseline levels by day 28. Minimal increases in ASCs were seen after a second vaccine dose at day 28. Antigen-specific IgG memory B cells persisted at day 180 postvaccination for both GI.1 and GII.4 VLPs. The overall trends in B-cell responses to vaccination were similar to the trends in the responses to infection, where there was a greater bias of an ASC response toward IgA and a memory B-cell response to IgG. The magnitude of the ASC and memory B-cell responses to the GI.1 VLP component of the vaccine was also comparable to that of the responses following GI.1 infection. The production of IgG memory B cells and persistence at day 180 is a key finding and underscores the need for future studies to determine if IgG memory B cells are a correlate of protection following vaccination. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168401.)","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00571-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34774768","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}
Gareth J Jones, Mick Coad, Bhagwati Khatri, Javier Bezos, Natalie A Parlane, Bryce M Buddle, Bernardo Villarreal-Ramos, R Glyn Hewinson, H Martin Vordermeier
{"title":"Tuberculin Skin Testing Boosts Interferon Gamma Responses to DIVA Reagents in Mycobacterium bovis-Infected Cattle.","authors":"Gareth J Jones, Mick Coad, Bhagwati Khatri, Javier Bezos, Natalie A Parlane, Bryce M Buddle, Bernardo Villarreal-Ramos, R Glyn Hewinson, H Martin Vordermeier","doi":"10.1128/CVI.00551-16","DOIUrl":"https://doi.org/10.1128/CVI.00551-16","url":null,"abstract":"<p><p><i>Mycobacterium bovis</i> BCG vaccination sensitizes cattle to bovine tuberculin, which compromises the use of the current bovine tuberculosis (TB) surveillance tests. Although the performance of a blood test (that utilizes antigens expressed by <i>Mycobacterium bovis</i> but not by BCG) capable of discriminating infected from vaccinated animals (DIVA interferon gamma test [DIT]) has been evaluated in naturally infected TB field reactors, there is a need to perform similar analysis in a BCG-vaccinated <i>M. bovis</i>-infected population. Furthermore, we explored different scenarios under which a DIT may be implemented alongside BCG vaccination: (i) serial testing to resolve potential false-positive skin test results or (ii) a standalone test to replace the single intradermal comparative cervical tuberculin (SICCT) skin test. Our results demonstrated significantly better relative test sensitivity when the DIT was evaluated in a serial test scenario. Direct comparison of pre- and post-skin test blood samples revealed that the SICCT test induced significant boosting of the gamma interferon response in <i>M. bovis</i>-infected animals to both the ESAT-6-CFP-10 and Rv3615c peptide cocktails that comprise the DIT, which persisted for the ESAT-6-CFP-10 reagent for at least 14 days. Importantly, no similar boosting effects were observed in noninfected BCG vaccinates, suggesting that DIVA blood testing after a recent skin test would have minimal impact on test specificity.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00551-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34845297","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}
Leidy Lagos, Julia I Tandberg, Urska Repnik, Preben Boysen, Erik Ropstad, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen
{"title":"Characterization and Vaccine Potential of Membrane Vesicles Produced by Francisella noatunensis subsp. orientalis in an Adult Zebrafish Model.","authors":"Leidy Lagos, Julia I Tandberg, Urska Repnik, Preben Boysen, Erik Ropstad, Deepa Varkey, Ian T Paulsen, Hanne C Winther-Larsen","doi":"10.1128/CVI.00557-16","DOIUrl":"https://doi.org/10.1128/CVI.00557-16","url":null,"abstract":"<p><p>Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. <i>Francisella noatunensis</i> subsp. <i>orientalis</i> is a Gram-negative, facultative intracellular bacterium that causes the disease francisellosis in fish. Francisellosis is commonly characterized as a chronic granulomatous disease with high morbidity and can result in high mortality depending on the host. In this study, we explored the potential of bacterial membrane vesicles (MVs) as a vaccine agent against <i>F. noatunensis</i> subsp. <i>orientalis</i> Bacterial MVs are spherical structures naturally released from the membrane of bacteria and are often enriched with selected bacterial components such as toxins and signaling molecules. MVs were isolated from broth-cultured <i>F. noatunensis</i> subsp. <i>orientalis</i> in the present work, and proteomic analysis by mass spectrometry revealed that MVs contained a variety of immunogenic factors, including the intracellular growth proteins IglC and IglB, known to be part of a <i>Francisella</i> pathogenicity island (FPI), as well as outer membrane protein OmpA, chaperonin GroEL, and chaperone ClpB. By using flow cytometry and electron microscopy, we observed that <i>F. noatunensis</i> subsp. <i>orientalis</i> mainly infects myelomonocytic cells, both <i>in vivo</i> and <i>in vitro</i> Immunization with MVs isolated from <i>F. noatunensis</i> subsp. <i>orientalis</i> protects zebrafish from subsequent challenge with a lethal dose of <i>F. noatunensis</i> subsp. <i>orientalis</i> To determine if MVs induce a typical acute inflammatory response, mRNA expression levels were assessed by quantitative real-time PCR. Expression of <i>tnfa</i>, <i>il1b</i>, and <i>ifng</i>, as well as <i>mhcii</i>, <i>mpeg1.1</i>, and <i>ighm</i>, was upregulated, thus confirming the immunogenic properties of <i>F. noatunensis</i> subsp. <i>orientalis</i>-derived MVs.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00557-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34845298","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}
Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea
{"title":"Correction for Bekkering et al., \"<i>In Vitro</i> Experimental Model of Trained Innate Immunity in Human Primary Monocytes\".","authors":"Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea","doi":"10.1128/CVI.00096-17","DOIUrl":"https://doi.org/10.1128/CVI.00096-17","url":null,"abstract":"• You may download this work for personal use only. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying this open access version If you believe that this document breaches copyright please contact us providing details and we will investigate your claim. Please direct all enquiries to puresupport@bib.sdu.dk","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00096-17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34972105","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":"Recent Progress in the Prevention of Serogroup B Meningococcal Disease.","authors":"Ian M Feavers, Martin C J Maiden","doi":"10.1128/CVI.00566-16","DOIUrl":"https://doi.org/10.1128/CVI.00566-16","url":null,"abstract":"<p><p>The widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subcapsular protein antigens, first with outer membrane vesicle (OMV) vaccines against epidemic outbreaks, and more recently on new multicomponent vaccines designed to offer better cross-protection against the antigenically diverse strains responsible for endemic disease. Because of the low incidence of meningococcal disease, the protective efficacy of these vaccines has not been determined in clinical studies, and their licensure has been based on serological data; however, the serological assays used to predict protective coverage have limitations. As a result, evidence of the effectiveness of these vaccines against different strains and the contribution of specific antigens to protection can only be provided by epidemiological analyses following their implementation in sufficiently large populations. The recent inclusion of the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero, in the infant immunization program in the UK has provided preliminary evidence that the vaccine is effective. Ongoing surveillance will provide valuable data on its longer-term impact and antigenic coverage. Further development of protein-based vaccines against meningococcal disease is anticipated to improve antigenic coverage and adjust to changes in circulating strains. At the same time, alternative immunization strategies may be explored to improve overall vaccine effectiveness by, for example, protecting the youngest infants or providing herd protection.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00566-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34868664","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}
Aneesh Vijayan, Ernesto Mejías-Pérez, Diego A Espinosa, Suresh C Raman, Carlos Oscar S Sorzano, Fidel Zavala, Mariano Esteban
{"title":"A Prime/Boost PfCS14K<sup>M</sup>/MVA-sPfCS<sup>M</sup> Vaccination Protocol Generates Robust CD8<sup>+</sup> T Cell and Antibody Responses to Plasmodium falciparum Circumsporozoite Protein and Protects Mice against Malaria.","authors":"Aneesh Vijayan, Ernesto Mejías-Pérez, Diego A Espinosa, Suresh C Raman, Carlos Oscar S Sorzano, Fidel Zavala, Mariano Esteban","doi":"10.1128/CVI.00494-16","DOIUrl":"https://doi.org/10.1128/CVI.00494-16","url":null,"abstract":"<p><p>Vaccines against the preerythrocytic stages of malaria are appealing because the parasite can be eliminated before disease onset and because they offer the unique possibility of targeting the parasite with both antibodies and T cells. Although the role of CD8<sup>+</sup> T cells in preerythrocytic malaria stages is well documented, a highly effective T cell-inducing vaccine remains to be advanced. Here we report the development of a prime-boost immunization regimen with the <i>Plasmodium falciparum</i> circumsporozoite protein (PfCS) fused to the oligomer-forming vaccinia virus A27 protein and a modified vaccinia virus Ankara (MVA) vector expressing PfCS. This protocol induced polyfunctional CD8<sup>+</sup> T cells with an effector memory phenotype and high PfCS antibody levels. These immune responses correlated with inhibition of liver-stage parasitemia in 80% and sterile protection in 40% of mice challenged with a transgenic <i>P. berghei</i> parasite line that expressed PfCS. Our findings underscore the potential of T and B cell immunization strategies for improving protective effectiveness against malaria.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00494-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34815897","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}