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vlp formulation

Ariane C Gomes, Anna Flace, Philippe Saudan, Franziska Zabel, Gustavo Cabral-Miranda, Aadil El Turabi, Vania Manolova, Martin F Bachmann
Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant...
2017: Frontiers in Immunology
Mona O Mohsen, Ariane C Gomes, Gustavo Cabral-Miranda, Caroline C Krueger, Fabiana Ms Leoratti, Jens V Stein, Martin F Bachmann
DNA rich in unmethylated CG motifs (CpGs) engage Toll-Like Receptor 9 (TLR-9) in endosomes and are well described stimulators of the innate and adaptive immune system. CpGs therefore can efficiently improve vaccines' immunogenicity. Packaging CpGs into nanoparticles, in particular into virus-like particles (VLPs), improves the pharmacological characteristics of CpGs as the protein shell protects them from DNAse activity and delivers the oligomers to the endosomal compartments of professional antigen presenting cells (APCs)...
February 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Diego Grando Módolo, Rodrigo Pinheiro Araldi, Jacqueline Mazzuchelli-de-Souza, Alexandre Pereira, Daniel Carvalho Pimenta, Letícia Maria Zanphorlin, Willy Beçak, Marcelo Menossi, Rita de Cassia Stocco, Rodrigo Franco de Carvalho
Bovine papillomatosis is an infectious disease that is caused by bovine papillomavirus (BPV), which results in important economic losses. However, no BPV vaccines or effective treatment methods are commercially available to date. Moreover, the absence of papillomavirus replication in vitro makes the use of recombinant protein a promising candidate for vaccine formulations. Hence, we developed an integrated study on the L1 capsid protein of BPV-1, obtained from a bacterial expression system, regarding its purification, biosafety, thermostability and immunogenicity...
February 17, 2017: Vaccine
Luis A Hernandez, Cathy L Miller, Eric M Vaughn
The increasing diversity of influenza strains circulating in swine herds escalates the potential for the emergence of novel pandemic viruses and highlights the need for swift development of new vaccines. Baculovirus has proven to be a flexible platform for the generation of recombinant forms of hemagglutinin (HA) including subunit, VLP-displayed, and baculovirus-displayed antigens. These presentations have been shown to be efficacious in mouse, chicken, and ferret models but little is known about their immunogenicity in pigs...
August 15, 2016: Veterinary Microbiology
Robert L Atmar, Frank Baehner, Jakob P Cramer, Eric Song, Astrid Borkowski, Paul M Mendelman
BACKGROUND: Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18-49 years. METHODS: Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 µg or 50 µg of GI.1 VLP and 50 µg GII...
September 15, 2016: Journal of Infectious Diseases
Chaoyun Shen, Zhiqiang Ku, Yu Zhou, Dapeng Li, Lili Wang, Ke Lan, Qingwei Liu, Zhong Huang
Coxsackievirus A6 (CA6) is emerging as one of the major causative agents of hand, foot, and mouth disease (HFMD) worldwide. However, no vaccine is currently available for preventing CA6 infection. Here, we report the development of a virus-like particle (VLP)-based recombinant vaccine for CA6. We produced CA6 VLPs in insect cells by infecting the cells with a baculovirus coexpressing the genes encoding CA6 P1 and 3CD. Biochemical analyses showed that the produced VLPs consisted of VP0, VP1, and VP3 capsid subunit proteins generated by the cleavage of P1 by 3CD...
July 25, 2016: Vaccine
Mathieu Boxus, Michel Fochesato, Agnès Miseur, Emmanuel Mertens, Najoua Dendouga, Sarah Brendle, Karla K Balogh, Neil D Christensen, Sandra L Giannini
UNLABELLED: At least 15 high-risk human papillomaviruses (HPVs) are linked to anogenital preneoplastic lesions and cancer. Currently, there are three licensed prophylactic HPV vaccines based on virus-like particles (VLPs) of the L1 major capsid protein from HPV-2, -4, or -9, including the AS04-adjuvanted HPV-16/18 L1 vaccine. The L2 minor capsid protein contains HPV-neutralizing epitopes that are well conserved across numerous high-risk HPVs. Therefore, the objective of our study was to assess the capacity to broaden vaccine-mediated protection using AS04-adjuvanted vaccines based on VLP chimeras of L1 with one or two L2 epitopes...
July 15, 2016: Journal of Virology
Newton Wahome, John M Hickey, David B Volkin, C Russell Middaugh
A critical element of vaccine formulation studies is the identification of chemical and physical degradation pathways that compromise structural integrity, and which may in turn affect the clinical safety and efficacy, of macromolecular antigens. Formulation development helps optimize and maintain the long-term storage stability and viability of vaccine antigens in pharmaceutically relevant dosage forms. The protocols presented in this manuscript highlight the use of accelerated stability studies for the formulation of influenza vaccine candidates including virus-like particles (VLP) and particle forming hemagglutinin (HA) antigens...
2016: Methods in Molecular Biology
Velasco Cimica, Hélène Boigard, Bipin Bhatia, John T Fallon, Alexandra Alimova, Paul Gottlieb, Jose M Galarza
Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants and children and represents an important global health burden for the elderly and the immunocompromised. Despite decades of research efforts, no licensed vaccine for RSV is available. We have developed virus-like particle (VLP)-based RSV vaccines assembled with the human metapneumovirus (hMPV) matrix protein (M) as the structural scaffold and the RSV fusion glycoprotein (F) in either the postfusion or prefusion conformation as its prime surface immunogen...
June 2016: Clinical and Vaccine Immunology: CVI
Sugandha Saboo, Ebenezer Tumban, Julianne Peabody, Denis Wafula, David S Peabody, Bryce Chackerian, Pavan Muttil
Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP)-based vaccine for HPV infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multicomponent excipient system and by optimizing the spray-drying parameters using a half-factorial design approach. Dry-powder VLPs were stable after spray drying and after long-term storage at elevated temperatures...
May 2, 2016: Molecular Pharmaceutics
Sen-Miao Tong, Ying Chen, Sheng-Hua Ying, Ming-Guang Feng
Many annotated fungal genomes harbour high proportions of hypothetical proteins with or without domains of unknown function (DUF). Here, three novel proteins (342-497 amino acids), each containing only a single large DUF1996 (231-250 residues) region with highly conserved head (DPIXXP) and tail (HXDXXXGW) signatures, were expressed as eGFP-tagged fusion proteins and shown to specifically localize in the vacuoles of Beauveria bassiana, a filamentous fungal entomopathogen; therefore, these proteins were named vacuole-localized proteins (VLPs)...
February 3, 2016: Scientific Reports
Farhat Khan, Mike Porter, Robert Schwenk, Margot DeBot, Philippe Saudan, Sheetij Dutta
Circumsporozoite protein (CSP) of Plasmodium falciparum is a promising malaria vaccine target. RTS,S, the most advanced malaria vaccine candidate consists of the central NANP repeat and carboxy-terminal region of CSP displayed on a hepatitis B virus-like particle (VLP). To build upon the success of RTS,S, we produced a near full-length Plasmodium falciparum CSP that also includes the conserved amino-terminal region of CSP. We recently showed that this soluble CSP, combined with a synthetic Toll-like-receptor-4 (TLR4) agonist in stable oil-in-water emulsion (GLA/SE), induces a potent and protective immune response in mice against transgenic parasite challenge...
2015: PloS One
Simon J Draper, Evelina Angov, Toshihiro Horii, Louis H Miller, Prakash Srinivasan, Michael Theisen, Sumi Biswas
Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms...
December 22, 2015: Vaccine
Xiaoli Wang, Zhiqiang Ku, Wenlong Dai, Tan Chen, Xiaohua Ye, Chao Zhang, Yingyi Zhang, Qingwei Liu, Xia Jin, Zhong Huang
Noroviruses are the main cause of severe viral gastroenteritis, which results in estimated 200,000 deaths each year, primarily in children in the developing world. Genogroup II.4 (GII.4) strains are responsible for the majority of norovirus outbreaks. Enterovirus 71 (EV71), the leading causative agent of hand, foot and mouth disease, has recently been prevalent in Asia-Pacific regions, resulting in significant morbidity and mortality in young children. However, no vaccine is commercially available for either norovirus GII...
October 26, 2015: Vaccine
Michael J McCluskie, Jennifer Thorn, David P Gervais, David R Stead, Ningli Zhang, Michelle Benoit, Janna Cartier, In-Jeong Kim, Keshab Bhattacharya, Jari I Finneman, James R Merson, Heather L Davis
Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~16, no aggregation (~100% monomer) and minimal adducts...
December 2015: International Immunopharmacology
Subhashini Jagu, Balusubramanyam Karanam, Joshua W Wang, Hatem Zayed, Margit Weghofer, Sarah A Brendle, Karla K Balogh, Kerstin Pino Tossi, Richard B S Roden, Neil D Christensen
Vaccination with the minor capsid protein L2, notably the 17-36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17-36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]...
October 13, 2015: Vaccine
Wai-Hong Wu, Tanwee Alkutkar, Balasubramanyan Karanam, Richard B S Roden, Gary Ketner, Okechukwu A Ibeanu
BACKGROUND: Infection by any one of 15 high risk human papillomavirus (hrHPV) types causes most invasive cervical cancers. Their oncogenic genome is encapsidated by L1 (major) and L2 (minor) coat proteins. Current HPV prophylactic vaccines are composed of L1 virus-like particles (VLP) that elicit type restricted immunity. An N-terminal region of L2 protein identified by neutralizing monoclonal antibodies comprises a protective epitope conserved among HPV types, but it is weakly immunogenic compared to L1 VLP...
September 11, 2015: Virology Journal
Alessandra Angelucci, Marcello G P Rosa
As highlighted by several contributions to this special issue, there is still ongoing debate about the number, exact location, and boundaries of the visual areas located in cortex immediately rostral to the second visual area (V2), i.e., the "third tier" visual cortex, in primates. In this review, we provide a historical overview of the main ideas that have led to four models of third tier cortex organization, which are at the center of today's debate. We formulate specific predictions of these models, and compare these predictions with experimental evidence obtained primarily in New World primates...
January 2015: Visual Neuroscience
Hanna Seitz, Lis Ribeiro-Müller, Elena Canali, Angelo Bolchi, Massimo Tommasino, Simone Ottonello, Martin Müller
Current prophylactic virus-like particle (VLP) human papillomavirus (HPV) vaccines are based on the L1 major capsid protein and provide robust but virus type-restricted protection. Moreover, VLP vaccines have a high production cost, require cold-chain storage, and are thus not readily implementable in developing countries, which endure 85% of the cervical cancer-related death burden worldwide. In contrast with L1, immunization with minor capsid protein L2 elicits broad cross-neutralization, and we previously showed that insertion of a peptide spanning amino acids 20-38 of L2 into bacterial thioredoxin (Trx) greatly enhances its immunogenicity...
October 2015: Cancer Prevention Research
Ebenezer Tumban, Pavan Muttil, Carolina Andrea A Escobar, Julianne Peabody, Denis Wafula, David S Peabody, Bryce Chackerian
An ideal prophylactic human papillomavirus (HPV) vaccine would provide broadly protective and long-lasting immune responses against all high-risk HPV types, would be effective after a single dose, and would be formulated in such a manner to allow for long-term storage without the necessity for refrigeration. We have developed candidate HPV vaccines consisting of bacteriophage virus-like particles (VLPs) that display a broadly neutralizing epitope derived from the HPV16 minor capsid protein, L2. Immunization with 16L2 VLPs elicited high titer and broadly cross-reactive and cross-neutralizing antibodies against diverse HPV types...
June 26, 2015: Vaccine
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