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Clinical and Vaccine Immunology: CVI

Sophie J Rhodes, Charlotte Sarfas, Gwenan M Knight, Andrew White, Ansar A Pathan, Helen McShane, Thomas G Evans, Helen Fletcher, Sally Sharpe, Richard G White
INTRODUCTION: Macaques play a central role in human tuberculosis(TB) vaccine development. Immune and challenge responses differ across macaque and human subpopulations. We determined which macaque subpopulations best predicted immune responses in different human subpopulations, using novel immunostimulation/immunodynamic modelling methods in a proof of concept study. METHODS: Data on IFN-γ secreting CD4+ T cells over time after recent BCG vaccination were available for 55 humans and 81 macaques...
January 11, 2017: Clinical and Vaccine Immunology: CVI
Katharina Richard, Barbara J Mann, Aiping Qin, Eileen M Barry, Robert K Ernst, Stefanie N Vogel
Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the USA. 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...
January 11, 2017: Clinical and Vaccine Immunology: CVI
Lea-Ann S Kirkham, Selma P Wiertsema, Karli J Corscadden, Tulia Mateus, Gemma L Mullaney, Guicheng Zhang, Peter C Richmond, Ruth B Thornton
BACKGROUND: The pneumococcus is a major otitis media (OM) pathogen but data are conflicting on whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titres to pneumococcal proteins and polysaccharides (vaccine and non-vaccine type), however the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titre, is considered to better correlate with protection from pneumococcal disease...
December 28, 2016: Clinical and Vaccine Immunology: CVI
L A Trotz-Williams, N J Mercer, K Paphitis, J M Walters, D Wallace, E Kristjanson, J Gubbay, T Mazzulli
BACKGROUND: In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes among vaccinated populations. This article describes an outbreak in a highly-vaccinated population in south-western Ontario, Canada and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. METHODS: During the outbreak, cases were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines...
December 21, 2016: Clinical and Vaccine Immunology: CVI
Amanda O'Brien, Clare Whelan, John B Clarke, Alastair Hayton, Neil J Watt, Gordon D Harkiss
Tuberculosis in goats is usually diagnosed clinically, at post-mortem, 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 management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in 100% of skin test positive animals in both serum and milk, and in 77...
December 14, 2016: Clinical and Vaccine Immunology: CVI
André G Loxton, Julia K Knaul, Leander Grode, Andrea Gutschmidt, Christiane Meller, Bernd Eisele, Hilary Johnstone, Gian van der Spuy, Jeroen Maertzdorf, Stefan H E Kaufmann, Anneke C Hesseling, Gerhard Walzl, Mark F Cotton
BACKGROUND: Tuberculosis is a global threat to which infants are especially vulnerable. Effective vaccines are required to protect infants from this devastating disease. VPM1002, a novel recombinant Bacille Calmette-Guérin (BCG) vaccine, previously shown to be safe and immunogenic in adults, was evaluated for safety in its intended target population, namely newborn infants in a region with high prevalence of tuberculosis. METHODS: A total of forty-eight newborns were vaccinated intradermally with VPM1002 (n=36) or BCG Danish strain (n=12) in a Phase II open-labelled, randomized trial with a 6 month follow-up period...
December 14, 2016: Clinical and Vaccine Immunology: CVI
R L Burton, J Antonello, D Cooper, D Goldblatt, K H Kim, B D Plikaytis, L Roalfe, D Wauters, F Williams, G L Xie, M H Nahm, M Akkoyunlu
Opsonophagocytic assays (OPAs) are routinely used for assessing the immunogenicity of pneumococcal vaccines, with OPA data often utilized for licensure of new vaccine formulations. However, no reference serum for pneumococcal OPAs is available, making evaluation of data among different laboratories difficult. This international collaboration was initiated to: 1) assign consensus opsonic indexes (OIs) to Pneumococcal Reference Serum Lot 007sp ("007sp") and a panel of calibration sera; and 2) determine if normalization with 007sp decreases the OPA variability among laboratories...
December 14, 2016: Clinical and Vaccine Immunology: CVI
Avital A Shimanovich, Amanda D Buskirk, Shannon J Heine, William C Blackwelder, Rezwanul Wahid, Karen L Kotloff, Marcela F Pasetti
Shigella is an important cause of diarrheal disease in young children living in developing countries. No approved vaccines are available, and the development of vaccine candidates has been hindered, among other reasons, by the lack of firm immunological correlates of protection. To address this gap in knowledge, we established quantitative assays to measure Shigella-specific serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity and investigated their potential association with protection against disease in humans...
December 7, 2016: Clinical and Vaccine Immunology: CVI
Susanne P Stoof, Mariëtte B van Ravenhorst, Debbie M van Rooijen, Richarda M de Voer, Fiona R M van der Klis, Greet J Boland, Elisabeth A M Sanders, Guy A M Berbers, Peter F Teunis
BACKGROUND: Adolescent vaccination is now considered the key factor to offer direct protection against meningococcal disease but also to reduce carriage and transmission and in this way establish herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. METHODS: Serum samples (n=1676) were drawn between 2006-2011 from individuals aged 9-18 years at time of primary MenCC vaccination in 2002...
November 23, 2016: Clinical and Vaccine Immunology: CVI
Ryan W J Steel, Brandon K Sack, Moriya Tsuji, Stefan H I Kappe
Plasmodium falciparum malaria remains the deadliest parasitic disease worldwide. Vaccines targeting the pre-erythrocytic sporozoite and liver stages have the potential to entirely prevent blood stage infection and disease, as well as onward transmission. Sporozoite surface and secreted proteins are leading candidates for inclusion in a pre-erythrocytic, antibody-based vaccine. Preclinical functional assays to identify humoral correlates of protection in vitro, and to validate novel sporozoite protein targets for inclusion in multi-subunit vaccines currently do not consider the interaction of sporozoite-targeting antibodies with other components of the immune system...
November 23, 2016: Clinical and Vaccine Immunology: CVI
Todd F Hatchette, Heidi Scholz, Shelly Bolotin, Natasha S Crowcroft, Colleen Jackson, Elizabeth McLachlan, Alberto Severini
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 have validated the test (off-label) to allow reporting of quantitative results. To do this, we used the 3(rd) anti-measles WHO standard to generate a calibration curve that allowed relative fluorescence intensity to be translated into quantitative antibody titer (Antibody Units/mL (AU/mL))...
November 16, 2016: Clinical and Vaccine Immunology: CVI
Steven C Derrick
In this issue of Clinical and Vaccine Immunology, Jensen et al. describe a dual purpose SIV/Mycobacterium tuberculosis vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures with SIV to become infected relative to non-immunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4(+) T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses and increased susceptibility to HIV...
November 9, 2016: Clinical and Vaccine Immunology: CVI
Leslie M Mayo-Smith, Jakub K Simon, Wilbur H Chen, Douglas Haney, Michael Lock, Caroline E Lyon, Stephen B Calderwood, Beth D Kirkpatrick, Mitchell Cohen, Myron M Levine, Marc Gurwith, Jason B Harris
One potential advantage of live attenuated bacterial vaccines is the ability to stimulate responses to antigens which are only expressed during the course of infection. To determine whether the live attenuated cholera vaccine CVD 103-HgR (Vaxchora™) results in antibody responses to the in vivo induced toxin-coregulated pilus antigen TcpA, we measured IgA and IgG responses to V. cholerae O1 El Tor TcpA in a subset of participants in a recently reported experimental challenge study. Participants were challenged with V...
November 9, 2016: Clinical and Vaccine Immunology: CVI
Serena Giuntini, Eduardo Lujan, Malick M Gibani, Christina Dold, Christine S Rollier, Andrew J Pollard, Dan M Granoff
BACKGROUND: MenB-4C is a meningococcal vaccine for prevention of serogroup B disease. The vaccine contains Factor H binding protein (FHbp) and three other antigens that can elicit serum bactericidal activity (SBA). For vaccine licensure, efficacy was inferred from SBA responses against three indicator strains. The relation between the results and broad protection against circulating genetically diverse strains is not known. METHODS: 20 adults were immunized with two doses of MenB-4C given 1 to 2 months apart...
November 9, 2016: Clinical and Vaccine Immunology: CVI
Katayi Mwila, Roma Chilengi, Michelo Simuyandi, Sallie R Permar, Sylvia Becker-Dreps
The role of maternal immunity received by infants either transplacentally or orally from breast milk on rotavirus vaccine (RV) performance is evaluated. Breast feeding withholding has no effect on vaccine response, 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...
November 9, 2016: Clinical and Vaccine Immunology: CVI
Daniel C Shippy, Justin J Lemke, Aubrey Berry, Kathryn Nelson, Murray E Hines, Adel M Talaat
Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the etiological agent of Johne's disease in ruminants. Johne's disease is an important enteric infection causing large economic losses associated with infected herds. In an attempt to fight this infection, we created two novel live-attenuated vaccine candidates with mutations in sigH and lipN (pgsH and pgsN, respectively). Earlier reports in mice suggested these vaccines are promising candidates to fight Johne's disease in ruminants. In this study, we tested the performance of the two constructs as vaccine candidates using the goat model of Johne's disease...
November 2, 2016: Clinical and Vaccine Immunology: CVI
David I Bernstein
Despite the clear need, progress towards a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest and several vaccine candidates are either in clinical trials or the trials are close. In this issue of the journal, Dr. Schleiss and colleagues show that a non -replicating lymphocytic choriomeningitis virus (rLCMV) vectored vaccine expressing CMV gB and/or pp65 induced B and T cells and improved pup survival in the guinea pig model of congenital CMV. The combination vaccine appeared to be the most effective...
October 26, 2016: Clinical and Vaccine Immunology: CVI
Elizabeth Diago-Navarro, Isabel Calatayud-Baselga, Donglei Sun, Camille Khairallah, Inderjit Mann, Amaia Ulacia-Hernando, Brian Sheridan, Meiqing Shi, Bettina C Fries
Hypervirulent Klebsiella pneumoniae (hvKp) strains are predicted to become a major threat in Asia if antibiotic resistance continues to spread. Anticapsular antibodies (Abs) were developed because disseminated infections caused by hvKp are associated with significant morbidity and mortality even with antibiotic sensitive strains. K1-serotype polysaccharide capsules (K1-CPS) are expressed by the majority of hvKp strains. In this study K1-CPS specific IgG Abs were generated by conjugation of K1-CPS to immunogenic Anthrax Protective Antigen (PA) protein...
October 26, 2016: Clinical and Vaccine Immunology: CVI
James R Deringer, Elkin G Forero-Becerra, Massaro W Ueti, Joshua E Turse, James E Futse, Susan M Noh, Guy H Palmer, Wendy C Brown
Within the protective outer membrane (OM) fraction of Anaplasma marginale, several vaccine candidates have emerged, including a family of OM proteins (OMPs) 7-9, which share sequence identity with each other and with the single protein OMP7 in the vaccine strain A. marginale subsp. centrale. A. marginale OMPs 7-9 are logical vaccine candidates because they are surface exposed, present in the OM immunogen and protective cross-linked OM proteins, recognized by immune serum IgG2 and T-cells in cattle immunized with OM, and recognized by immune serum IgG2 from cattle immunized with the A...
October 26, 2016: Clinical and Vaccine Immunology: CVI
Mark R Schleiss, Ursula Berka, Elizabeth Watson, Mario Aistleithner, Bettina Kiefmann, Bastien Mangeat, Elizabeth C Swanson, Peter A Gillis, Nelmary Hernandez-Alvarado, Claudia Fernández-Alarcón, Jason C Zabeli, Daniel D Pinschewer, Anders Lilja, Michael Schwendinger, Farshad Guirakhoo, Thomas P Monath, Klaus Orlinger
Subunit vaccines for prevention of congenital cytomegalovirus (CMV) infection based on glycoprotein B (gB) and pp65 are in clinical trials, but it is unclear whether simultaneous vaccination with both antigens enhances protection. We undertook evaluation of a novel bivalent vaccine based on non-replicating lymphocytic choriomeningitis virus (rLCMV) vectors expressing a cytoplasmic tail-deleted gB (gB(dCt)), and full-length pp65 from human CMV in mice. Immunization with the gB(dCt) vector alone elicited a comparable gB-binding antibody response, and a superior neutralizing response, to that elicited by adjuvanted subunit gB...
October 26, 2016: Clinical and Vaccine Immunology: CVI
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