Abstract:
:This work describes the formulation design and development of a novel protein based adjuvant, a double mutant of heat labile toxin (dmLT), based on knowledge of the protein's structural integrity and physicochemical degradation pathways. Various classes of pharmaceutical excipients were screened for their stabilizing effect on dmLT during exposure to thermal and agitation stresses as monitored by high throughput analytical assays for dmLT degradation. Sucrose, phosphate, sodium chloride, methionine and polysorbate-80 were identified as potential stabilizers that protected dmLT against either conformational destabilization, aggregation/particle formation or chemical degradation (e.g., Met oxidation and Lys glycation). Different combinations and concentrations of the selected stabilizers were then evaluated to further optimize dmLT stability while maintaining pharmaceutically acceptable ranges of solution pH and osmolality. The effect of multiple freeze-thaw (FT) cycles on the physical stability of candidate bulk formulations was also examined. Increasing the polysorbate-80 concentration to 0.1% in the lead candidate bulk formulation mitigated the loss of protein mass during FT. This formulation development study enabled the design of a new bulk formulation of the dmLT adjuvant and provides flexibility for future use in combination with a variety of different vaccine dosage forms with different antigens.
journal_name
Vaccinejournal_title
Vaccineauthors
Toprani VM,Sahni N,Hickey JM,Robertson GA,Middaugh CR,Joshi SB,Volkin DBdoi
10.1016/j.vaccine.2017.03.101subject
Has Abstractpub_date
2017-10-04 00:00:00pages
5471-5480issue
41eissn
0264-410Xissn
1873-2518pii
S0264-410X(17)30475-9journal_volume
35pub_type
杂志文章相关文献
VACCINE文献大全abstract::Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2017.10.036
更新日期:2017-12-04 00:00:00
abstract::T-lymphocyte responses to influenza vaccination were measured in healthy young and older adult volunteers. All participants were vaccinated with the 1995-96 trivalent influenza vaccine. Cytokine and granzyme B levels were measured in peripheral blood mononuclear cells (PBMC) cultures after virus stimulation, prior to ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(98)00133-9
更新日期:1998-11-01 00:00:00
abstract::Flagellin of Pseudomonas aeruginosa is an important vaccine candidate. N-terminal domains are highly conserved in both type a and type b flagellins. The efficacy of gold nanoparticles (AuNPs) conjugated to N-terminal domains of P. aeruginosa flagellin (flagellin(1-161)), as an immunogen in mice, has been assessed. The...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2016.01.041
更新日期:2016-03-14 00:00:00
abstract::We examined the immunogenicity and protective efficacy of a combined DNA vaccine that included six genes encoding immunodominant antigens from Mycobacterium tuberculosis and Brucella abortus. The IL-12 adjuvant system was used for immunization in combination with the combined DNA vaccine (DNA-IL-12(+)). Mice immunized...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2007.06.061
更新日期:2007-09-17 00:00:00
abstract::Vaccination is an effective strategy to prevent pneumococcal diseases. Currently, licensed vaccines include the pneumococcal polysaccharide vaccine (PPSV) and the pneumococcal conjugate vaccine (PCV), which target some of the most common of the 94 serotypes of S. pneumoniae based on their capsular composition. However...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2018.11.015
更新日期:2019-01-03 00:00:00
abstract::We aim to develop a method that confers rapid protection against foot-and-mouth disease (FMD) by passive immunization with recombinant llama single-domain antibody fragments (VHHs). Previously constructed genetic fusions of two VHHs (VHH2s) that either neutralizes FMDV or binds to porcine immunoglobulin to increase th...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2009.01.110
更新日期:2009-03-18 00:00:00
abstract::In this study we describe our attempts to improve the immunogenicity of a synthetic epitope-based vaccine. The vaccine consists of an epitope (P25) that is recognised by CD4+ helper T cells and the target epitope luteinising hormone releasing hormone (LHRH). We show that replacement of the single cysteine residue with...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2005.04.015
更新日期:2005-08-15 00:00:00
abstract:BACKGROUND AND PURPOSE:Varicella disease is a risk factor for pediatric Arterial Ischemic Stroke (AIS). Isolated case reports have emerged suggesting that varicella vaccination may also pose a risk for AIS. METHODS:This retrospective population-based cohort study assessed the risk of AIS in children who received a var...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2018.04.012
更新日期:2018-05-11 00:00:00
abstract::Formalin-killed Streptococcus difficile strains used as vaccines delivered intraperitoneally were able to protect tilapia against a challenge of 100 LD50. The protection obtained was not strain specific. A vaccine based on an S. difficile extract containing 50% protein conjugated to alum also protected tilapia challen...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/0264-410x(94)00067-w
更新日期:1995-06-01 00:00:00
abstract::Mycobacterium w (Mw), is a cultivable, non-pathogenic mycobacterium and has been tried extensively as an immunomodulator in leprosy. This has been found to be safe and has shown beneficial immunoprophylactic effect in population based, double blind placebo controlled trials in North India. These effects were also obse...
journal_title:Vaccine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vaccine.2007.12.025
更新日期:2008-02-26 00:00:00
abstract::Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immuni...
journal_title:Vaccine
pub_type: 杂志文章,评审
doi:10.1016/j.vaccine.2013.06.107
更新日期:2013-11-22 00:00:00
abstract::Sporozoite vaccination of both humans and rodents elicits potent anti-malarial immunity, but the dose of sporozoites and the number of immunizations required varies with vaccination approach. Here we examine the immunological basis for superior protection afforded from single-dose vaccination with virulent sporozoites...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2013.11.058
更新日期:2014-01-16 00:00:00
abstract::The protection elicited by the intramuscular injection of two plasmid DNAs encoding Leishmania major cysteine proteinase type I (CPb) and type II (CPa) was evaluated in a murine model of experimental cutaneous leishmaniasis. BALB/c mice were immunized either separately or with a cocktail of the two plasmids expressing...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(01)00081-0
更新日期:2001-05-14 00:00:00
abstract::The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deam...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2013.03.002
更新日期:2013-04-26 00:00:00
abstract::Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-d...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2009.12.045
更新日期:2010-03-02 00:00:00
abstract::Two modified live attenuated vaccines against the disease Rift Valley fever (RVF) have been tested for safety and efficacy in young calves. The RVF Smithburn vaccine produced in South Africa and used successfully to prevent and control the disease in endemic sub-Saharan countries was compared to the candidate vaccine ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2011.05.055
更新日期:2011-08-05 00:00:00
abstract::Measles, mumps, rubella and varicella are viral infections which can implicate seriously long-term sequelae of infected individuals or even the unborn child. Vaccines against the individual diseases have long been available. Global measles vaccination is estimated to have prevented more than 20million deaths during 20...
journal_title:Vaccine
pub_type: 杂志文章,评审
doi:10.1016/j.vaccine.2017.07.051
更新日期:2018-08-28 00:00:00
abstract::In a previous study, children 18 to 36 months of age and seropositive for respiratory syncytial virus (RSV) were vaccinated with an RSV subunit vaccine (PFP-1) consisting of the viral fusion protein. Vaccines developed substantial increases in anti-fusion and neutralizing antibody and exhibited protection against RSV ...
journal_title:Vaccine
pub_type: 临床试验,杂志文章
doi:10.1016/0264-410x(94)90316-6
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:Patients with inflammatory rheumatic diseases are at higher risk for influenza and current guidelines recommend vaccination for this group of patients. The aim of this study was to evaluate the vaccination coverage and predictors for influenza vaccination among patients with inflammatory rheumatic diseases. ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2018.06.065
更新日期:2018-08-06 00:00:00
abstract::We have covalently conjugated an N-terminus Plasmodium vivax apical membrane antigen-1 (AMA-1) peptide to functionalized carbon nanotubes (f-CNT). Immunological characterization of this molecular conjugate revealed that the immunogen-AMA-1 peptide was appropriately presented after being conjugated to CNTs as well as b...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2008.08.014
更新日期:2008-10-29 00:00:00
abstract::We describe here two very potent adjuvant systems which are thought to work directly on antigen specific lymphocytes, thus by-passing the normal route for adjuvants, which is to activate antigen presenting cells (APCs) inducing release of inflammatory cytokines with resultant side effects of local and systemic reactog...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2005.01.105
更新日期:2006-04-12 00:00:00
abstract:BACKGROUND:This study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults....
journal_title:Vaccine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vaccine.2018.04.034
更新日期:2018-07-25 00:00:00
abstract::We assessed the tetanus immunity of the general Dutch population and of religious groups refusing vaccination by means of population-based study to evaluate the effect of tetanus vaccination. More than 95% of those born after the introduction of routine vaccination had tetanus antitoxin levels above the minimum protec...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(99)00186-3
更新日期:1999-08-20 00:00:00
abstract::Recombinant hepatitis B vaccine has been used widely in the world since 1991. The side effects of hepatitis B vaccine are seen rarely. In this paper, we present clinical and laboratory progress of an infant who gets severe thrombocytopenia after the second dosage hepatitis B vaccine. Our case is different from other c...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2008.09.062
更新日期:2008-12-02 00:00:00
abstract::Gram-negative bacterial outer membrane proteins (Omps) have an important role in pathogenesis and signal reception. We previously reported that Acinetobacter OmpA (AbOmpA) induced maturation of bone marrow-derived dendritic cells (BMDCs) and that AbOmpA-primed DCs produced IL-12 which generated Th1 CD4(+) T-cells. We ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2011.01.036
更新日期:2011-03-16 00:00:00
abstract::Modified vaccinia Ankara (MVA) recombinants expressing single or multiple RSV surface proteins (F or G) are promising potential vaccines. We studied humoral and cellular responses induced by MVA-F and MVA-G in mice, comparing them to a formalin inactivated RSV preparation (FI-RSV) known to increase disease severity. M...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2004.05.015
更新日期:2004-11-25 00:00:00
abstract::Glycoconjugate vaccines have been proven safe and effective against various diseases in children. Although these vaccines have a history of effectiveness, there are still many unanswered questions to be addressed, including conjugate interference when multiple vaccines are administered at one time, expansion of seroty...
journal_title:Vaccine
pub_type: 杂志文章,评审
doi:10.1016/j.vaccine.2010.04.072
更新日期:2010-06-17 00:00:00
abstract::The first 4 years of the 21st century have been an exciting time for tuberculosis (TB) research. After more than a half-century, the first new vaccines for TB are beginning to enter human clinical trials. Based on advances in proteomics and genomics, new vaccine candidates are filling the preclinical pipeline and our ...
journal_title:Vaccine
pub_type: 杂志文章,评审
doi:10.1016/j.vaccine.2005.01.060
更新日期:2005-03-18 00:00:00
abstract::We previously demonstrated that recombinant raccoonpox (RCN) virus could serve as a vector for an influenza vaccine. RCN constructs expressing the hemagglutinin (HA) from H5N1 viruses were immunogenic in chickens. In the current study, we generated several recombinant RCN constructs expressing influenza (H5N1) antigen...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2012.08.018
更新日期:2012-10-05 00:00:00
abstract:BACKGROUND:Seasonal influenza infections among young children in China lead to substantial numbers of hospitalizations and financial burden. This study assessed the seasonal influenza vaccine effectiveness (VE) against laboratory confirmed medically attended influenza illness among children in Suzhou, China, from Octob...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2016.03.056
更新日期:2016-05-05 00:00:00