Abstract:
:One of the greatest challenges to HCV vaccine development is the induction of effective immune responses using recombinant proteins or vectors. In order to better understand which vaccine-induced antibodies contribute to neutralization of HCV the quality of polyclonal anti-E1E2 antibody responses in immunized mice and chimpanzees was assessed at the level of epitope recognition using peptide scanning and neutralization of chimeric 1a/2a, 1b/2a and 2a HCVcc after blocking or affinity elution of specific antibodies. Mice and chimpanzees were immunized with genotype 1a (H77) HCV gpE1E2; all samples contained cross-neutralizing antibody against HCVcc. By functionally dissecting the polyclonal immune responses we identified three new regions important for neutralization within E1 (aa264-318) and E2 (aa448-483 and aa496-515) of the HCV glycoproteins, the third of which (aa496-515) is highly conserved (85-95%) amongst genotypes. Antibodies to aa496-515 were isolated by affinity binding and elution from the serum of a vaccinated chimpanzee and found to specifically neutralize chimeric 1a/2a, 1b/2a and 2a HCVcc. IC50 titres (IgG ng/mL) for the aa496-515 eluate were calculated as 142.1, 239.37 and 487.62 against 1a/2a, 1b/2a and 2a HCVcc, respectively. Further analysis demonstrated that although antibody to this new, conserved neutralization epitope is efficiently induced with recombinant proteins in mice and chimpanzees; it is poorly induced during natural infection in patients and chimpanzees (7 out of 68 samples positive) suggesting the epitope is poorly presented to the immune system in the context of the viral particle. These findings have important implications for the development of HCV vaccines and strategies designed to protect against heterologous viruses. The data also suggest that recombinant or synthetic antigens may be more efficient at inducing neutralizing antibodies to certain epitopes and that screening virally infected patients may not be the best approach for finding new cross-reactive epitopes.
journal_name
Vaccinejournal_title
Vaccineauthors
Kachko A,Kochneva G,Sivolobova G,Grazhdantseva A,Lupan T,Zubkova I,Wells F,Merchlinsky M,Williams O,Watanabe H,Ivanova A,Shvalov A,Loktev V,Netesov S,Major MEdoi
10.1016/j.vaccine.2011.10.045subject
Has Abstractpub_date
2011-12-09 00:00:00pages
69-77issue
1eissn
0264-410Xissn
1873-2518pii
S0264-410X(11)01665-3journal_volume
30pub_type
杂志文章相关文献
VACCINE文献大全abstract::EG95 is a recombinant vaccine protein that elicits protection against hydatid disease in sheep. Previous studies have shown that the host-protective epitopes on EG95 depend on correct conformation and cannot be represented by simple "linear" peptides. By screening random peptide phage display libraries with polyclonal...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2008.11.096
更新日期:2009-02-11 00:00:00
abstract::To assess the efficacy of the intradermal route of administration of hepatitis A vaccine we conducted a study in hospital laboratory workers. Forty-three volunteers were given three different combinations of intradermal and intramuscular hepatitis A vaccine and compared with 18 controls given intramuscular vaccine onl...
journal_title:Vaccine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0264-410x(94)90303-4
更新日期:1994-05-01 00:00:00
abstract::A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportuni...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2011.10.013
更新日期:2011-11-28 00:00:00
abstract::Two double-blind randomised controlled studies (phase I and I/II) were performed to assess for the first time the safety and immunogenicity of a recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine in 148 healthy adult volunteers. All candidate vaccine formulations had a good safety profile and were well tolerat...
journal_title:Vaccine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vaccine.2007.04.008
更新日期:2007-06-11 00:00:00
abstract::In Balb/c mice, the sterile protective immunity induced by immunization with radiation-attenuated Plasmodium yoelii sporozoites is eliminated by in vivo depletion of CD8+ T lymphocytes, suggesting that cytotoxic T lymphocytes (CTL) against malaria antigens expressed on infected hepatocytes are required for mediating t...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/0264-410x(92)90436-n
更新日期:1992-01-01 00:00:00
abstract:INTRODUCTION:Self-reported measles vaccination coverage is frequently used to inform vaccination strategies in resource-poor settings. However, little is known to what extent this is a reliable indicator of underlying seroprotection, information that could provide guidance ensuring the success of measles control and el...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2015.07.007
更新日期:2015-08-26 00:00:00
abstract::Plague is a zoonotic disease caused by Yersinia pestis, an etiological agent of pneumonic and bubonic plague. There is a need for an improved plague vaccine that may overcome the limitation of presently available whole cell vaccine. An alternative approach described here, is the use of protective epitopes from immunod...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2006.01.031
更新日期:2006-04-12 00:00:00
abstract::The immunogenicity of two vector-based vaccines, either given alone or in a prime-boost regimen, was investigated. Cynomolgus macaques were immunised with modified vaccinia virus Ankara (MVA) expressing simian immunodeficiency virus (SIV)macJ5 env, gag-pol, nef, rev, and tat genes (MVA-SIVmac) or primed with a Semliki...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(01)00034-2
更新日期:2001-05-14 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::Domestic ducks remain a major source of zoonotic Salmonella enterica infections for man worldwide and approaches to protection should include vaccine-mediated immunity. With this in mind we developed several genetically defined mutants in a virulent duck Salmonella typhimurium isolate TT-1. From initial tests for viru...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2015.09.004
更新日期:2015-10-13 00:00:00
abstract::The development of potent adjuvants, conditioning innate and adaptative immunity, particularly CTL responses, has become currently a hot point in the rational design of vaccines for cancer immunotherapy. We have described a new approach, in which gangliosides are incorporated into vesicles from Neisseria meningitidis ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2005.08.111
更新日期:2006-03-24 00:00:00
abstract::Comparative analyses of murine dendritic cells (DC) isolated from the skin and from the intestinal mucosa after exposure to cholera toxin and its non-toxic B subunit disclose striking differences regarding the migratory and functional behaviour of these cells. The nature of the epithelial microenvironment, especially ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2005.01.124
更新日期:2006-04-12 00:00:00
abstract::The virulence and immunogenicity of a wild-type respiratory syncytial (RS) virus together with four temperature sensitive (ts) mutants derived from this isolate were tested by intranasal inoculation into adult volunteers. Resistance to challenge correlated with neutralizing antibody titres in nasal secretions and to a...
journal_title:Vaccine
pub_type: 临床试验,杂志文章
doi:10.1016/0264-410x(90)90051-m
更新日期:1990-06-01 00:00:00
abstract::Newcastle disease virus (NDV), an avian virus, is being evaluated for the development of vectored human vaccines against emerging pathogens. Previous studies of NDV-vectored vaccines in a mouse model suggested their potency after delivery by injection or by the intranasal route. We compared the efficacy of various rou...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2009.01.009
更新日期:2009-03-04 00:00:00
abstract::Due to ongoing recombination and mutations, HIV permanently escapes from neutralizing antibody (nAb) responses of the host. By the masking of epitopes or shedding of gp120, HIV-1 further impedes an efficient neutralization by Abs. Therefore, nAbs responses of the host are chasing behind a rapidly evolving virus and ma...
journal_title:Vaccine
pub_type: 杂志文章,评审
doi:10.1016/j.vaccine.2008.11.050
更新日期:2008-12-30 00:00:00
abstract::Infectious bronchitis virus (IBV) as an avian coronavirus is still posing a persistent and imminent threat to the poultry industry worldwide. Here we report that transfection of Sf9 cells with a single recombinant baculovirus encoding M and S proteins resulted in the assembly of IBV VLPs; this is the first report that...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2013.09.024
更新日期:2013-11-12 00:00:00
abstract::Intranasal live attenuated influenza vaccine (LAIV) has potential for self-administration (SA) by adults and adolescents, which could save time and cost in mass vaccination settings. Participants in a study of LAIV in adults (n=4561) selected either SA or health care provider (HCP) administration and were followed for...
journal_title:Vaccine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vaccine.2012.12.028
更新日期:2013-01-30 00:00:00
abstract::Pertussis has re-emerged as a public health problem in Canada in recent years, emphasizing concerns about the effectiveness of the currently licensed whole-cell vaccine. Following a 1994 outbreak in Nova Scotia, we conducted a case-control study of 483 children aged < 10 years to assess vaccine effectiveness. Ninety-t...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(96)00176-4
更新日期:1997-02-01 00:00:00
abstract::There is currently much interest in generating cytotoxic T lymphocyte (CTL) responses against tumor antigens as a therapy for cancer. In this study mouse fibroblasts (H-2(b)) were genetically modified to express a costimulatory B7.1 and a mature interleukin (IL)-18, and then loaded with an ovalbumin (OVA) epitope (SII...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2003.12.015
更新日期:2004-06-30 00:00:00
abstract::The literature on natural infections with Japanese encephalitis virus in Japan and subclinical:clinical infection rates was summarized. To detect natural infections, conventional serologic methods were used in the past, while nonstructural 1 protein-based methods have been used recently. Annual infection rates in huma...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2009.09.052
更新日期:2009-11-23 00:00:00
abstract::Passive immunization of mice with 131 micrograms of the non-neutralizing monoclonal antibody (mAb) 18A2B2, directed against the A subgroup epitope of the G glycoprotein of respiratory syncytial virus Long strain (RSV), confers protection against viral i.n. challenge. The role of the Fc fragment of this antibody as wel...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/0264-410x(95)00222-m
更新日期:1996-04-01 00:00:00
abstract::Effective immunoprophylaxis directed against the pre-erythrocytic stages of the malaria parasite requires a vaccine that can elicit humoral and cell mediated immunity in individuals of diverse genetic background. In order for a synthetic peptide malaria vaccine to meet these requirements, problems associated with gene...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/s0264-410x(97)00238-7
更新日期:1998-04-01 00:00:00
abstract:BACKGROUND:Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the searc...
journal_title:Vaccine
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vaccine.2012.04.007
更新日期:2012-06-08 00:00:00
abstract::The efficacy of antibody immunity against Streptococcus pneumoniae stems from the ability of opsonic, serotype (ST)-specific antibodies to pneumococcal capsular polysaccharide (PPS) to facilitate killing of the homologous ST by host phagocytes. However, PPS-specific antibodies have been identified that are protective ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2010.08.061
更新日期:2010-11-03 00:00:00
abstract:INTRODUCTION:Observational studies of influenza vaccine effectiveness often study persons seeking medical care for acute respiratory infection (ARI). We conducted a pilot study to determine if vaccine effectiveness could be estimated in the general population with a novel rolling cross-sectional survey sampling design ...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2014.09.051
更新日期:2014-11-12 00:00:00
abstract::Dengue fever is a growing public health concern around the world and despite vaccine development efforts, there are currently no effective dengue vaccines. In the present study we report the induction of protective antibodies against dengue virus by DNA immunization with domain III (DIII) region of the envelope protei...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2004.12.028
更新日期:2005-05-16 00:00:00
abstract::'Children represent the most vulnerable segment of every society--and they are our present and future. Good health, especially of children, promotes personal and national development. Scientific progress, matched with improved capacities of all countries to immunize their children, provides an unparalleled opportunity...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/0264-410x(92)90323-c
更新日期:1992-01-01 00:00:00
abstract::With declining influenza vaccine coverage in the elderly in recent years in France, we aimed at assessing the benefits of seasonal influenza vaccination, based on available data for observed mortality, vaccine coverage and vaccine effectiveness. To estimate the annual number of deaths avoided by vaccination in the peo...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2015.01.023
更新日期:2015-02-25 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::EBA-175 protein is used as ligand in Plasmodium falciparum binding to erythrocytes. Evidence shows that conserved peptide 1815 from this protein having high red blood cell binding ability plays an important role in the invasion process. This peptide is neither immunogenic nor protective. Residues were substituted by a...
journal_title:Vaccine
pub_type: 杂志文章
doi:10.1016/j.vaccine.2004.08.052
更新日期:2005-02-18 00:00:00