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https://www.readbyqxmd.com/read/27374905/particle-and-subunit-based-hemagglutinin-vaccines-provide-protective-efficacy-against-h1n1-influenza-in-pigs
#1
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
https://www.readbyqxmd.com/read/27354368/rapid-responses-to-2-virus-like-particle-norovirus-vaccine-candidate-formulations-in-healthy-adults-a-randomized-controlled-trial
#2
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
https://www.readbyqxmd.com/read/27340093/virus-like-particle-based-vaccine-against-coxsackievirus-a6-protects-mice-against-lethal-infections
#3
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
https://www.readbyqxmd.com/read/27147749/broad-cross-protection-is-induced-in-preclinical-models-by-a-human-papillomavirus-vaccine-composed-of-l1-l2-chimeric-virus-like-particles
#4
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
https://www.readbyqxmd.com/read/27076313/formulation-studies-during-preclinical-development-of-influenza-hemagglutinin-and-virus-like-particle-vaccine-candidates
#5
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
https://www.readbyqxmd.com/read/27030590/novel-respiratory-syncytial-virus-like-particle-vaccine-composed-of-the-postfusion-and-prefusion-conformations-of-the-f-glycoprotein
#6
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
https://www.readbyqxmd.com/read/27019231/optimized-formulation-of-a-thermostable-spray-dried-virus-like-particle-vaccine-against-human-papillomavirus
#7
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
https://www.readbyqxmd.com/read/26839279/three-duf1996-proteins-localize-in-vacuoles-and-function-in-fungal-responses-to-multiple-stresses-and-metal-ions
#8
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)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26571021/head-to-head-comparison-of-soluble-vs-q%C3%AE-vlp-circumsporozoite-protein-vaccines-reveals-selective-enhancement-of-nanp-repeat-responses
#9
COMPARATIVE STUDY
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
https://www.readbyqxmd.com/read/26458807/recent-advances-in-recombinant-protein-based-malaria-vaccines
#10
REVIEW
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
https://www.readbyqxmd.com/read/26424606/a-bivalent-virus-like-particle-based-vaccine-induces-a-balanced-antibody-response-against-both-enterovirus-71-and-norovirus-in-mice
#11
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
https://www.readbyqxmd.com/read/26404190/anti-nicotine-vaccines-comparison-of-adjuvanted-crm197-and-qb-vlp-conjugate-formulations-for-immunogenicity-and-function-in-non-human-primates
#12
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
https://www.readbyqxmd.com/read/26382603/durable-immunity-to-oncogenic-human-papillomaviruses-elicited-by-adjuvanted-recombinant-adeno-associated-virus-like-particle-immunogen-displaying-l2-17-36-epitopes
#13
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
https://www.readbyqxmd.com/read/26362430/capsid-display-of-a-conserved-human-papillomavirus-l2-peptide-in-the-adenovirus-5-hexon-protein-a-candidate-prophylactic-hpv-vaccine-approach
#14
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
https://www.readbyqxmd.com/read/26241792/resolving-the-organization-of-the-third-tier-visual-cortex-in-primates-a-hypothesis-based-approach
#15
REVIEW
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
https://www.readbyqxmd.com/read/26170394/robust-in-vitro-and-in-vivo-neutralization-against-multiple-high-risk-hpv-types-induced-by-a-thermostable-thioredoxin-l2-vaccine
#16
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
https://www.readbyqxmd.com/read/26003490/preclinical-refinements-of-a-broadly-protective-vlp-based-hpv-vaccine-targeting-the-minor-capsid-protein-l2
#17
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
https://www.readbyqxmd.com/read/25912208/phase-ii-studies-to-select-the-formulation-of-a-multivalent-hpv-l1-virus-like-particle-vlp-vaccine
#18
Alain Luxembourg, Darron Brown, Celine Bouchard, Anna R Giuliano, Ole-Erik Iversen, Elmar A Joura, Mary E Penny, Jaime A Restrepo, Josefina Romaguera, Roger Maansson, Erin Moeller, Michael Ritter, Joshua Chen
Our objective was to develop a multivalent prophylactic HPV vaccine that protects against infection and disease caused by HPV16/18 (oncogenic types in existing prophylactic vaccines) plus additional oncogenic types by conducting 3 Phase II studies comparing the immunogenicity (i.e., anti-HPV6/11/16/18 geometric mean titers [GMT]) and safety of 7 vaccine candidates with the licensed quadrivalent HPV6/11/16/18 vaccine (qHPV vaccine) in young women ages 16-26. In the first study (Study 1), subjects received one of 3 dose formulations of an 8-valent HPV6/11/16/18/31/45/52/58 vaccine or qHPV vaccine (control)...
2015: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/25903355/genotype-considerations-for-virus-like-particle-based-bivalent-norovirus-vaccine-composition
#19
Maria Malm, Kirsi Tamminen, Suvi Lappalainen, Hanni Uusi-Kerttula, Timo Vesikari, Vesna Blazevic
Norovirus (NoV) genogroup I (GI) and GII are responsible for most human infections with NoV. Because of the high genetic variability of NoV, natural infection does not induce sufficient protective immunity to different genotypes or to variants of the same genotype and there is little or no cross-protection against different genogroups. NoV-derived virus-like particles (VLPs) are promising vaccine candidates that induce high levels of NoV-specific humoral and cellular immune responses. It is believed that a bivalent NoV vaccine consisting of a representative VLP from GI and GII is a minimum requirement for an effective vaccine...
June 2015: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/25751641/lessons-learned-from-successful-human-vaccines-delineating-key-epitopes-by-dissecting-the-capsid-proteins
#20
REVIEW
Xiao Zhang, Lu Xin, Shaowei Li, Mujin Fang, Jun Zhang, Ningshao Xia, Qinjian Zhao
Recombinant VLP-based vaccines have been successfully used against 3 diseases caused by viral infections: Hepatitis B, cervical cancer and hepatitis E. The VLP approach is attracting increasing attention in vaccine design and development for human and veterinary use. This review summarizes the clinically relevant epitopes on the VLP antigens in successful human vaccines. These virion-like epitopes, which can be delineated with molecular biology, cryo-electron microscopy and x-ray crystallographic methods, are the prerequisites for these efficacious vaccines to elicit functional antibodies...
2015: Human Vaccines & Immunotherapeutics
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