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immunogenicity vaccine

Li Yu, Mark T Esser, Judith Falloon, Tonya Villafana, Harry Yang
Immunogenicity data from phase 1 vaccine studies can be difficult to interpret, especially in seropositive populations and when multiple assays are used. We developed 3 statistical methods (Youden index [YI] threshold, receiver-operating characteristic relative to baseline [ROC-B], and ROC of postdose levels [ROC-P]) to characterize complex immunogenicity data by assessing the proportion of a study population that achieved values above thresholds. The YI method calculates a single threshold per assay. Both ROC methods construct ROC curves for individual assays and surfaces for assay combinations to assess degree of separation of postdose values from a reference distribution; the ROC-B method uses overall predose values as the reference distribution and the ROC-P method uses pooled postdose values...
June 18, 2018: Human Vaccines & Immunotherapeutics
Wayne Paes, Adam Dowle, Jamie Coldwell, Andrew Leech, Tim Ganderton, Andrzej Brzozowski
Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterial pathogen, and the leading cause of infectious blindness worldwide. We have recently shown that immunization with the highly conserved antigenic passenger domain of recombinant Ct polymorphic membrane protein D (rPmpD) is protective in the mouse model of Ct genital tract infection, and previously, that ocular anti-rPmpD antibodies are elicited following vaccination. However, the mechanisms governing the assembly and structure-function relationship of PmpD are unknown...
2018: PloS One
Vera Kadlecek, Charissa Fay Borja-Tabora, Susanne Eder-Lingelbach, Salvacion Gatchalian, Sigrid Kiermayr, Benjamin Sablan, Michael Kundi, Christian Taucher, Katrin L Dubischar
BACKGROUND: An inactivated Vero cell culture derived Japanese encephalitis virus vaccine (IXIARO) requires a booster dose 1 year after primary schedule for long-term antibody persistence in adults. OBJECTIVES: To evaluate immunogenicity and safety of a booster dose in children aged 2 months to <18 years. METHODS: A randomized, controlled open-label study in the Philippines. Three hundred children vaccinated with IXIARO in a previous trial were randomized 1:1 to receive either no booster or a booster 12 months after initiation of the primary series...
June 15, 2018: Pediatric Infectious Disease Journal
Emmanuel Amlabu, Henrietta Mensah-Brown, Prince B Nyarko, Ojo-Ajogu Akuh, Grace Opoku, Philip Ilani, Richard Oyagbenro, Kwame Asiedu, Yaw Aniweh, Gordon A Awandare
Plasmodium falciparum erythrocyte invasion is a multi-step process that involves a spectrum of interactions that are not well characterized. We have characterized a 113 kDa immunogenic protein PF3D7_1431400 (PF14_0293) that possesses coiled-coil structures. The protein is localized on the surfaces of both merozoites and gametocytes, hence the name PlasmodiumfalciparumSurface Related Antigen (PfSRA). The processed 32 kDa fragment of PfSRA binds normal human erythrocytes with different sensitivities to enzyme treatments...
April 18, 2018: Journal of Infectious Diseases
Xia Li, Xiupeng Wang, Atsuo Ito
Vaccines, one of the most effective and powerful public health measures, have saved countless lives over the past century and still have a tremendous global impact. As an indispensable component of modern vaccines, adjuvants play a critical role in strengthening and/or shaping a specific immune response against infectious diseases as well as malignancies. The application of nanotechnology provides the possibility of precisely tailoring the building blocks of nanoadjuvants towards modern vaccines with the desired immune response...
June 18, 2018: Chemical Society Reviews
F Ghaffarifar
DNA vaccines are considered as third-generation vaccines. The recombinant DNA technology plays an important role in the production of DNA vaccines. These vaccines are intended to increase DNA insertion and translation in the cell, activate CD4+ T cells, and enhance cytotoxic T-lymphocyte induction and antibody production. DNA vaccines are safe with few side effects in humans and animals. Their immunogenicity can be improved by the use of suitable adjuvants and proper delivery systems. In recent years, strategies have been developed to increase the efficacy of DNA vaccines through electroporation, as well as the use of cytokines, genetically engineered vectors, liposomes, and micro- or nanoparticles...
May 2018: Drugs of Today
Samira Ebrahimi, Hassan Mohabatkar
Streptococcal bacteria are among dangerous human pathogens with major prevalence worldwide. A good vaccine against streptococcal bacteria should have epitopes that confer protection from infection by different streptococcal bacteria types. we aimed was to recognize the most immunogenic and conserved epitopes of streptococcal bacteria, which could be a potential candidate for vaccine development. Nineteen different M proteins of different streptococcal bacteria were chosen and analyzed. Nine-mer epitopes able to simulate both cells mediate and humoral immunity were predicted...
March 2018: Molecular Biology Research Communications
Qinying Yan, Zhigang Cheng, Houming Liu, Wanshui Shan, Zhide Cheng, Xuyong Dai, Yun Xue, Fan Chen
Tuberculosis (TB) remains a major global public health problem. New immunization methods against TB are urgently needed. Plasmid DNA with a microneedle patch is a potentially attractive strategy to improve the immune effect. A DNA vaccine encoding the secreted protein Ag85B of Mycobacterium tuberculosis was immunized in the skin using microneedles, which can improve protective immunity compared to conventional intramuscular (IM) injection. There is no significant difference between microneedle patch (MNP) and IM immunization when the immunizing dose is low (4...
June 14, 2018: Vaccine
Kamila Hladíková, Simona Partlová, Vladimír Koucký, Jan Bouček, Jean-Francois Fonteneau, Michal Zábrodský, Ruth Tachezy, Marek Grega, Radek Špíšek, Anna Fialová
BACKGROUND: Human papillomavirus (HPV) type 16 infection is one of the most important etiological agents of oropharyngeal squamous cell carcinoma. Patients with HPV-associated carcinomas of the head and neck were reported to have a better clinical outcome than patients with HPV-negative tumors. Because HPV16 E6 and E7 oncoproteins are highly immunogenic and constitutively expressed, HPV-specific T cell immunity may play the key role in improving the prognosis of these patients. METHODS: Tumor-derived T cells were expanded in high levels of IL-2 and stimulated with HPV16 E6/E7 peptides in the presence or absence of anti-PD-1 monoclonal antibody nivolumab and soluble Tim-3...
July 2018: Oral Oncology
Bai Xuejuan, Wang Dongfang, Yinping Liu, Xiao Li, Yan Liang, Yourong Yang, Junxian Zhang, Minggui Lin, Wu Xueqiong
There is an urgent need for a more effective vaccine against tuberculosis (TB). Cytotoxic T lymphocytes (CTLs) play a critical role in combating Mycobacterium tuberculosis (M.tb). The identification of novel CTL epitopes is essential for the design of peptide-based vaccines. In this study, we predicted CTL epitope peptides of M.tb antigen Rv2629 restricted by HLA-A2, using bioinformatics methods. The affinity and stability of binding of these peptides with HLA-A2 molecules were detected by flow cytometry. Their ability to induce CTLs generation was determined in peripheral blood mononuclear cells (PBMCs) from healthy uninfected subjects, Latent tuberculosis infection (LTBI) subjects, and TB patients ex vivo...
June 14, 2018: Immunology Letters
Daniel S Dias, Patrícia A F Ribeiro, Vívian T Martins, Daniela P Lage, Lourena E Costa, Miguel A Chávez-Fumagalli, Fernanda F Ramos, Thaís T O Santos, Fernanda Ludolf, Jamil S Oliveira, Tiago A O Mendes, Eduardo S Silva, Alexsandro S Galdino, Mariana C Duarte, Bruno M Roatt, Daniel Menezes-Souza, Antonio L Teixeira, Eduardo A F Coelho
Vaccination seems to be the best approach to control visceral leishmaniasis (VL). Resistance against infection is based on the development of a Th1 immune response characterized by the production of interferons-γ (IFN-γ), interleukin-12 (IL-12), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α), among others. A number of antigens have been tested as potential targets against the disease; few of them are able to stimulate human immune cells. In the present study, 1 prediction of MHC class I and II molecules-specific epitopes in the amino acid sequences of 3 Leishmania proteins: 1 hypothetical, prohibitin, and small glutamine-rich tetratricopeptide repeat-containing proteins, was performed using bioinformatics tools, and a T-cell epitopes-based recombinant chimeric protein was constructed, synthetized and purified to be evaluated in invitro and in vivo experiments...
May 22, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
Julie M Diamond, Claire Vanpouille-Box, Sheila Spada, Nils-Petter Rudqvist, Jessica Chapman, Beatrix Ueberheide, Karsten A Pilones, Yasmeen Sarfraz, Silvia C Formenti, Sandra Demaria
Radiotherapy (RT) used at immunogenic doses leads to accumulation of cytosolic double-stranded DNA (dsDNA) in cancer cells, which activates type I IFN (IFN-I) via the cGAS/STING pathway. Cancer cell-derived IFN-I is required to recruit BATF3-dependent dendritic cells (DCs) to poorly immunogenic tumors and trigger antitumor T-cell responses in combination with immune checkpoint blockade. We have previously demonstrated that the exonuclease TREX1 regulates radiation immunogenicity by degrading cytosolic dsDNA...
June 15, 2018: Cancer Immunology Research
Lizhu Yi, Zhendong Qin, Hanzuo Lin, Yang Zhou, Jiabo Li, Zhen Xu, Sarath Babu V, Li Lin
Red-spotted grouper nervous necrosis virus (RGNNV) is one of the most important viruses which mainly infects the larva of marine and freshwater fish with high mortality and affects the fishery industry worldwide. Currently, there are no effective vaccines available for the fish larva infected with NNV. Immunoglobulin yolk (IgY) origin of oviparous animals is passed from the blood serum and concentrated in the egg yolk. With the advantages of high yield, cost-effectiveness, and high stability, IgY can be widely used in passive immunization, especially in young animals in which adaptive immunity is not fully developed...
June 12, 2018: Fish & Shellfish Immunology
Mei-Le Keck, Florian Wrensch, Brian G Pierce, Thomas F Baumert, Steven K H Foung
Hepatitis C virus (HCV) continues to spread worldwide with an annual increase of 1.75 million new infections. The number of HCV cases in the U.S. is now greater than the number of HIV cases and is increasing in young adults because of the opioid epidemic sweeping the country. HCV-related liver disease is the leading indication of liver transplantation. An effective vaccine is of paramount importance to control and prevent HCV infection. While this vaccine will need to induce both cellular and humoral immunity, this review is focused on the required antibody responses...
2018: Frontiers in Immunology
Céline Maréchal, Himal Lal, Airi Poder, Murdo Ferguson, Igwebuike Enweonye, Thomas C Heineman, Caroline Hervé, Paul Rheault, Jaak Talli, Dominique Wauters, Lidia Oostvogels
BACKGROUND: This study evaluated immunogenicity and safety of the adjuvanted recombinant zoster vaccine (RZV) when the first dose was co-administered with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults aged ≥50 years. METHODS: In this open label, multi-center study (NCT02045836), participants were randomized 1:1 to receive either the first dose of RZV and PPSV23, co-administered at Day 0 and the second dose of RZV at Month 2 (Co-Ad group), or PPSV23 at Day 0, the first dose of RZV at Month 2 and second dose of RZV at Month 4 (Control group)...
June 11, 2018: Vaccine
Shuyi Wang, Juan Xue, Ping Lu, Chunshan Ni, Hao Cheng, Rui Han, Stijn van der Veen
OBJECTIVES: The rise in multidrug resistant Neisseria gonorrhoeae poses a threat to healthcare, while the development of an effective vaccine has remained elusive due to antigenic and phase variability of surface-expressed proteins. In the current study, we identified a fully conserved surface expressed protein and characterized its suitability as a vaccine antigen. METHODS: An in silico approach was used to predict surface-expressed proteins and analyze sequence conservation and phase variability...
June 11, 2018: Journal of Infection
Peng Zhang, Jason Gorman, Hui Geng, Qingbo Liu, Yin Lin, Yaroslav Tsybovsky, Eden P Go, Barna Dey, Tsion Andine, Alice Kwon, Mit Patel, Deepali Gururani, Ferzan Uddin, Christina Guzzo, Raffaello Cimbro, Huiyi Miao, Krisha McKee, Gwo-Yu Chuang, Loïc Martin, Francesca Sironi, Mauro S Malnati, Heather Desaire, Edward A Berger, John R Mascola, Michael A Dolan, Peter D Kwong, Paolo Lusso
The HIV-1 envelope (Env) spike is a trimer of gp120/gp41 heterodimers that mediates viral entry. Binding to CD4 on the host cell membrane is the first essential step for infection but disrupts the native antigenic state of Env, posing a key obstacle to vaccine development. We locked the HIV-1 Env trimer in a pre-fusion configuration, resulting in impaired CD4 binding and enhanced binding to broadly neutralizing antibodies. This design was achieved via structure-guided introduction of neo-disulfide bonds bridging the gp120 inner and outer domains and was successfully applied to soluble trimers and native gp160 from different HIV-1 clades...
June 13, 2018: Cell Host & Microbe
James B Munro
No immunogen has been found that elicits a broadly neutralizing antibody (bNAb) response sufficient for development into an HIV vaccine. In this issue of Cell Host and Microbe, Zhang et al. (2018) rationally design an HIV envelope glycoprotein variant that provides new hope that such an immunogen may be attainable.
June 13, 2018: Cell Host & Microbe
Remon Abu-Elyazeed, William Jennings, Randall Severance, Michael Noss, Adrian Caplanusi, Michael Povey, Ouzama Henry
The introduction of vaccination programs against measles, mumps, and rubella (MMR) led to significant global reduction in morbidity and mortality from these diseases. The currently recommended MMR vaccination schedule in the United States of America comprises 2 vaccine doses typically administered at 12-15 months and 4-6 years, respectively. Considering recent outbreaks in the USA, catch-up vaccination with an additional dose of MMR vaccine could contribute to outbreak control and community protection. This phase III, observer-blind, randomized controlled trial (NCT02058563) assessed the immunogenicity and safety of a dose of the MMR-RIT vaccine (Priorix, GSK) compared to MMR II vaccine (control; M-M-R II, Merck&Co Inc...
June 14, 2018: Human Vaccines & Immunotherapeutics
Rajan Kumar Pandey, Rupal Ojha, Amit Mishra, Vijay Kumar Prajapati
The Zika virus is a rapidly spreading Aedes mosquito-borne sickness, which creates an unanticipated linkage birth deformity and neurological turmoil. This study represents the use of the combinatorial immunoinformatics approach to develop a multiepitope subunit vaccine using the structural and nonstructural proteins of the Zika virus. The designed subunit vaccine consists of cytotoxic T-lymphocyte and helper T-lymphocyte epitopes accompanied by suitable adjuvant and linkers. The presence of humoral immune response specific B-cell epitopes was also confirmed by B-cell epitope mapping among vaccine protein...
June 14, 2018: Journal of Cellular Biochemistry
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