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At least 613 records · Page 34Linked to original sources
PubMed2005

Identification of novel tick salivary gland proteins for vaccine development.

Methods currently used to control Ixodes scapularis ticks rely principally on acaricidal applications which suffer from a number of limitations. Recently, host vaccination against ticks has been shown to be a promising alternative tick control method. In tick salivary glands, numerous genes are induced during the feeding process. Many of these newly expressed proteins are secreted in tick saliva and may play a role in modulating host immune responses and pathogen transmission. We have performed suppression subtraction hybridization to identify unique I. scapularis salary gland proteins specifically expressed during engorgement. We have cloned and sequenced ten unique salivary gland-associated cDNAs that are up-regulated during feeding. The protein products of these genes represent potential vaccine candidates for use in the control of ticks and to prevent transmission of tick-borne diseases.

Amino Acid Sequence↗
PubMed1999

Lyme disease: pathogenesis and vaccine development.

Research of recent years on Lyme disease has greatly increased our understanding on antigenic structures and genotypic variability of the aetiological agent, Borrelia (B.) burgdorferi sensu lato, as well as on mechanisms underlying host-parasite interactions and induction/mode of action of protective immune responses. A vaccine formula on the basis of the outer surface lipoprotein A (OspA), previously developed in our laboratory, has successfully been tested in a clinical trial involving nearly 10,000 subjects in the USA. The OspA vaccine is unique in that it protects the mammalian host from infection by eliminating spirochaetes from the vector, but does not cure an established disease. This is because spirochaetes express OspA exclusively in the tick, but not when transmitted into the vertebrate host. For Europe, a more complex vaccine formula is required in order to achieve full protection. This is due to the higher degree of heterogeneity of OspA molecules among isolates of B. burgdorferi in Europe and the inability of the monovalent vaccine to convey complete cross-protection.

Animals↗
PubMed1985

Vaccine development for the control of cholera and related toxin-induced diarrhoeal diseases.

The toxin-induced diarrhoeal diseases in greatest need of effective vaccines for use in control programmes are cholera and diarrhoea due to enterotoxigenic Escherichia coli. Such vaccines, whether consisting of inactivated immunogens or live attenuated organisms, should be administered by the oral route to stimulate the gut mucosal immune system to a maximal extent. For optimal efficacy they should probably contain or produce immunogens evoking both antibacterial and antitoxic immunity that can interfere in a synergistically cooperative manner with colonization as well as toxin action (binding) events in the pathogenesis. The actual or predicted advantages and limitations of oral vaccines based on protective antigen cocktails and different approaches to live, attenuated organisms are discussed. A conclusion is that effective vaccines could play an important role in the control of diarrhoeal disease by reducing mortality and morbidity, and ideally also the transmission of disease.

Cholera↗
PubMed2006

Strategies for development of vaccines for control of ixodid tick species.

Ticks are distributed worldwide and impact human and animal health, as well as food animal production. Control of ticks has been primarily by application of acaricides, which has resulted in selection of resistant ticks and environmental pollution. Vaccines have been shown to be a feasible tick control method that offers a cost-effective, environmentally friendly alternative to chemical control. However, identification of tick-protective antigens remains the limiting step in vaccine development. Tick antigens exposed naturally to the host during tick feeding and those concealed have both shown promise as candidate vaccine antigens. Development of vaccines against multiple tick species may be possible using highly conserved tick-protective antigens or by antigens showing immune cross-reaction to different tick species. Vaccines made from a combination of key protective antigens may greatly enhance vaccine efficacy. Preliminary studies have suggested the possibility of vaccine strategies directed toward both tick control and the blocking of pathogen transmission. Characterization of the tick genomes will have a great impact on the discovery of new protective antigens. The future of research directed toward tick vaccine development is exciting because of new and emerging technologies for gene discovery, and vaccine formulation and delivery.

Animals↗
PubMed2002

Hepatitis C virus envelope glycoproteins and potential for vaccine development.

HCV envelope glycoproteins play an important role in the initiation of viral infection. The functional dichotomy of the individual HCV glycoproteins was investigated using VSV/HCV pseudotype virus. Surprisingly, VSV/HCV pseudotype virus generated from either E1 or E2 displayed infectivity of a number of mammalian cells. The use of pseudotyped virus has allowed us to better understand the similar and divergent properties of E1 and E2 glycoproteins decorating the envelope of HCV. The serum pseudotype virus neutralizing activity in patient sera did not exhibit a correlation with the infecting HCV genotype or virus load. HCV E2 glycoprotein induces a weak neutralizing antibody response, however the neutralization function was augmented by complement. Taken together, these observations suggest a role for both the glycoproteins in HCV attachment and entry into susceptible host cells. An understanding of HCV entry and strategies appropriate for mimicking cell surface molecules may help in the development of new therapeutic modalities against HCV infection. Furthermore, incorporation of the HCV glycoproteins in a candidate vaccine may offer protection, although additional work is necessary to enhance their immunogenicity.

Animals↗
PubMed1986

New findings in live, attenuated hepatitis A vaccine development.

Strain CR326F of hepatitis A virus, derived from a fecal specimen of Costa Rican patient 033-03, was passed 15 times in fetal rhesus monkey kidney (FRhK6) cell cultures plus eight times in human diploid lung (MRC5) cell cultures to yield variant F and 16 times in MRC5 cell cultures to yield variant F'. Both variants were purified by limit dilution passages. Virulence for marmosets was assessed at six different passage levels, including variants F and F'. There was a gradual loss of virulence with in vitro passage. Variant F retained slight virulence for marmosets; variant F' showed no evidence of virulence. Both variants induced hepatitis A antibody in most marmosets that received them, and the animals were immune to infection when challenged. Variants F and F' were also assessed in chimpanzees. As in marmosets, F retained slight virulence but F' did not. Experimental vaccines made from variants F and F' were then inoculated parenterally into adult human volunteers. A portion of recipients of variant F showed brief, low-order enzyme elevations; none was seen in recipients of F', although their occurrence could not be totally ruled out. As in the animal models, F' appeared more attenuated than F. Most persons developed hepatitis A antibody, indicating the feasibility of developing a live, attenuated hepatitis A vaccine for human beings.

Animals↗