The Experts below are selected from a list of 31518 Experts worldwide ranked by ideXlab platform

Michele D Spring - One of the best experts on this subject based on the ideXlab platform.

Cindy Tamminga - One of the best experts on this subject based on the ideXlab platform.

Martha Sedegah - One of the best experts on this subject based on the ideXlab platform.

  • sterile immunity to malaria after dna prime Adenovirus boost immunization is associated with effector memory cd8 t cells targeting ama1 class i epitopes
    PLOS ONE, 2014
    Co-Authors: Martha Sedegah, Michael R Hollingdale, Fouzia Farooq, Harini Ganeshan, Maria Belmonte, Bjoern Peters, Alessandro Sette, Jun Huang, Shannon Mcgrath, Esteban Abot
    Abstract:

    Background Fifteen volunteers were immunized with three doses of plasmid DNA encoding P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) and boosted with Human Adenovirus-5 (Ad) expressing the same antigens (DNA/Ad). Four volunteers (27%) demonstrated sterile immunity to controlled Human malaria infection and, overall, protection was statistically significantly associated with ELISpot and CD8+ T cell IFN-γ activities to AMA1 but not CSP. DNA priming was required for protection, as 18 additional subjects immunized with Ad alone (AdCA) did not develop sterile protection. Methodology/Principal Findings We sought to identify correlates of protection, recognizing that DNA-priming may induce different responses than AdCA alone. Among protected volunteers, two and three had higher ELISpot and CD8+ T cell IFN-γ responses to CSP and AMA1, respectively, than non-protected volunteers. Unexpectedly, non-protected volunteers in the AdCA trial showed ELISpot and CD8+ T cell IFN-γ responses to AMA1 equal to or higher than the protected volunteers. T cell functionality assessed by intracellular cytokine staining for IFN-γ, TNF-α and IL-2 likewise did not distinguish protected from non-protected volunteers across both trials. However, three of the four protected volunteers showed higher effector to central memory CD8+ T cell ratios to AMA1, and one of these to CSP, than non-protected volunteers for both antigens. These responses were focused on discrete regions of CSP and AMA1. Class I epitopes restricted by A*03 or B*58 supertypes within these regions of AMA1 strongly recalled responses in three of four protected volunteers. We hypothesize that vaccine-induced effector memory CD8+ T cells recognizing a single class I epitope can confer sterile immunity to P. falciparum in Humans. Conclusions/Significance We suggest that better understanding of which epitopes within malaria antigens can confer sterile immunity and design of vaccine approaches that elicit responses to these epitopes will increase the potency of next generation gene-based vaccines.

  • Human Adenovirus 5 vectored plasmodium falciparum nmrc m3v ad pfca vaccine encoding csp and ama1 is safe well tolerated and immunogenic but does not protect against controlled Human malaria infection
    Human Vaccines & Immunotherapeutics, 2013
    Co-Authors: Cindy Tamminga, Martha Sedegah, Santina Maiolatesi, Charlotte Fedders, Sharina Reyes, Anatalio Reyes, Carlos Vasquez, Yolanda Alcorta, Ilin Chuang, Michele D Spring
    Abstract:

    Background: In a prior study, a DNA prime / Adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccine) induced 27% protection against controlled Human malaria infection (CHMI). To investigate the contribution of DNA priming, we tested the efficacy of Adenovirus vaccine alone (NMRC-M3V-Ad-PfCA ) in a Phase 1 clinical trial.Methodology/Principal Findings: The regimen was a single intramuscular injection with two non-replicating Human serotype 5 adenovectors encoding CSP and AMA1, respectively. One x 1010 particle units of each construct were combined prior to administration. The regimen was safe and well-tolerated. Four weeks later, 18 study subjects received P. falciparum CHMI administered by mosquito bite. None were fully protected although one showed delayed onset of parasitemia. Antibody responses were low, with geometric mean CSP ELISA titer of 381 (range < 50–1626) and AMA1 ELISA of 4.95 µg/mL (range 0....

  • Human Adenovirus 5 vectored plasmodium falciparum nmrc m3v ad pfca vaccine encoding csp and ama1 is safe well tolerated and immunogenic but does not protect against controlled Human malaria infection
    Human Vaccines & Immunotherapeutics, 2013
    Co-Authors: Cindy Tamminga, Martha Sedegah, Santina Maiolatesi, Charlotte Fedders, Sharina Reyes, Anatalio Reyes, Carlos Vasquez, Yolanda Alcorta, Ilin Chuang, Michele D Spring
    Abstract:

    Background: In a prior study, a DNA prime / Adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccin...

Sarah C Gilbert - One of the best experts on this subject based on the ideXlab platform.

  • Immunity, safety and protection of an Adenovirus 5 prime - Modified Vaccinia virus Ankara boost subunit vaccine against Mycobacterium avium subspecies paratuberculosis infection in calves
    Veterinary Research, 2014
    Co-Authors: Tim J Bull, Sarah C Gilbert, Christina Vrettou, Richard Linedale, Catherine Mcguinnes, Sam Strain, Jim Mcnair, Jayne C Hope
    Abstract:

    Vaccination is the most cost effective control measure for Johne¿s disease caused by Mycobacterium avium subspecies paratuberculosis (MAP) but currently available whole cell killed formulations have limited efficacy and are incompatible with the diagnosis of bovine tuberculosis by tuberculin skin test. We have evaluated the utility of a viral delivery regimen of non-replicative Human Adenovirus 5 and Modified Vaccinia virus Ankara recombinant for early entry MAP specific antigens (HAV) to show protection against challenge in a calf model and extensively screened for differential immunological markers associated with protection. We have shown that HAV vaccination was well tolerated, could be detected using a differentiation of infected and vaccinated animals (DIVA) test, showed no cross-reactivity with tuberculin and provided a degree of protection against challenge evidenced by a lack of faecal shedding in vaccinated animals that persisted throughout the 7 month infection period. Calves given HAV vaccination had significant priming and boosting of MAP derived antigen (PPD-J) specific CD4+, CD8+ IFN-? producing T-cell populations and, upon challenge, developed early specific Th17 related immune responses, enhanced IFN-? responses and retained a high MAP killing capacity in blood. During later phases post MAP challenge, PPD-J antigen specific IFN-? and Th17 responses in HAV vaccinated animals corresponded with improvements in peripheral bacteraemia. By contrast a lack of IFN-?, induction of FoxP3+ T cells and increased IL-1? and IL-10 secretion were indicative of progressive infection in Sham vaccinated animals. We conclude that HAV vaccination shows excellent promise as a new tool for improving control of MAP infection in cattle.

  • modified vaccinia virus ankara based vaccine vectors induce apoptosis in dendritic cells draining from the skin via both the extrinsic and intrinsic caspase pathways preventing efficient antigen presentation
    Journal of Virology, 2012
    Co-Authors: Efrain Guzman, Sarah C Gilbert, Carolina Cubilloszapata, Bryan Charleston, Matthew G Cottingham, Helen Prentice, Jayne Hope
    Abstract:

    Dendritic cells (DC) are potent antigen-presenting cells and central to the induction of immune responses following infection or vaccination. The collection of DC migrating from peripheral tissues by cannulation of the afferent lymphatic vessels provides DC which can be used directly ex vivo without extensive in vitro manipulations. We have previously used bovine migrating DC to show that recombinant Human Adenovirus 5 vectors efficiently transduce afferent lymph migrating DEC-205CD11cCD8 DC (ALDC). We have also shown that recombinant modified vaccinia virus Ankara (MVA) infects ALDC in vitro, causing downregulation of costimulatory molecules, apoptosis, and cell death. We now show that in the bovine system, modified vaccinia virus Ankara-induced apoptosis in DC draining from the skin occurs soon after virus binding via the caspase 8 pathway and is not associated with viral gene expression. We also show that after virus entry, the caspase 9 pathway cascade is initiated. The magnitude of T cell responses to mycobacterial antigen 85A (Ag85A) expressed by recombinant MVA-infected ALDC is increased by blocking caspase-induced apoptosis. Apoptotic bodies generated by recombinant MVA (rMVA)-Ag85A-infected ALDC and containing Ag85A were phagocytosed by noninfected migrating ALDC expressing SIRPvia actin-dependent phagocytosis, and these ALDC in turn presented antigen. However, the addition of fresh ALDC to MVA-infected cultures did not improve on the magnitude of the T cell responses; in contrast, these noninfected DC showed downregulation of major histocompatibility complex class II (MHC-II), CD40, CD80, and CD86. We also observed that MVA-infected ALDC promoted migration of DEC-205 SIRP CD21 DC as well as CD4 and CD8 T cells independently of caspase activation. These in vitro studies show that induction of apoptosis in DC by MVA vectors is detrimental to the subsequent induction of T cell responses.

  • prevalence of serum neutralizing antibodies against chimpanzee Adenovirus 63 and Human Adenovirus 5 in kenyan children in the context of vaccine vector efficacy
    Vaccine, 2009
    Co-Authors: Maria Dudareva, Laura Andrews, Sarah C Gilbert, Philip Bejon, Kevin Marsh, Jedidah Mwacharo, Oscar Kai, Alfredo Nicosia, Adrian V S Hill
    Abstract:

    Vaccination against Plasmodium falciparum malaria could reduce the worldwide burden of this disease, and decrease its high mortality in children. Replication-defective recombinant Adenovirus vectors carrying P. falciparum epitopes may be useful as part of a vaccine that raises cellular immunity to the pre-erythrocytic stage of malaria infection. However, existing immunity to the Adenovirus vector results in antibody-mediated neutralization of the vaccine vector, and reduced vaccine immunogenicity. Our aim was to examine a population of children who are at risk from P. falciparum malaria for neutralizing immunity to replication-deficient recombinant chimpanzee Adenovirus 63 vector (AdC63), compared to Human Adenovirus 5 vector (AdHu5). We measured 50% and 90% vector neutralization titers in 200 individual sera, taken from a cohort of children from Kenya, using a secreted alkaline phosphatase neutralization assay. We found that 23% of the children (aged 1-6 years) had high-titer neutralizing antibodies to AdHu5, and 4% had high-titer neutralizing antibodies to AdC63. Immunity to both vectors was age-dependent. Low-level neutralization of AdC63 was significantly less frequent than AdHu5 neutralization at the 90% neutralization level. We conclude that AdC63 may be a useful vector as part of a prime-boost malaria vaccine in children.

Kelly M Lager - One of the best experts on this subject based on the ideXlab platform.

  • overcoming maternal antibody interference by vaccination with Human Adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of swine influenza virus
    Veterinary Microbiology, 2006
    Co-Authors: Ronald D Wesley, Kelly M Lager
    Abstract:

    Sows and gilts lack immunity to Human Adenovirus 5 (Ad-5) vectored vaccines so immunogens of swine pathogens can be expressed with these vaccines in order to immunize suckling piglets that have interfering, maternally derived antibodies. In this study 7-day-old piglets, that had suckled H3N2 infected gilts, were sham-inoculated with a non-expressing Ad-5 vector or given a primary vaccination with replication-defective Ad-5 viruses expressed the H3 hemagglutinin and the nucleoprotein of swine influenza virus (SIV) subtype H3N2. The hemagglutination inhibition (HI) titer of the sham-inoculated group (n = 12) showed continued antibody decay whereas piglets vaccinated with Ad-5 SIV (n = 23) developed an active immune response by the second week post-vaccination. At 4 weeks-of-age when the HI titer of the sham-inoculated group had decayed to 45, the sham-inoculated group and half of the Ad-5 SIV vaccinated pigs were boosted with a commercial inactivated SIV vaccine. The boosted pigs that had been primed in the presence of maternal interfering antibodies had a strong anamnestic response while sham-inoculated pigs did not respond to the commercial vaccine. Two weeks after the booster vaccination the pigs were challenged with a non-homologous H3N2 virulent SIV. The efficacy of the vaccination protocol was demonstrated by abrogation of clinical signs, by clearance of challenge virus from pulmonary lavage fluids, by markedly reduced virus shedding in nasal secretions, and by the absence of moderate or severe SIV-induced lung lesions. These recombinant Ad-5 SIV vaccines are useful for priming the immune system to override the effects of maternally derived antibodies which interfere with conventional SIV vaccines.

  • evaluation of a recombinant Human Adenovirus 5 vaccine administered via needle free device and intramuscular injection for vaccination of pigs against swine influenza virus
    American Journal of Veterinary Research, 2005
    Co-Authors: Ronald D Wesley, Kelly M Lager
    Abstract:

    Objective—To evaluate the safety and efficacy of a Human Adenovirus-5 vaccine for protecting weaned pigs against swine influenza virus subtype H3N2 infection when administered via 2 injection methods. Animals—76 pigs. Procedure—6 groups of weaned pigs received a 10- fold serial dilution of recombinant Adenovirus expressing H3 hemagglutinin and a constant amount of recombinant Adenovirus expressing nucleoprotein, either via a needle-free injection device or by traditional IM injection. In each group of 10 pigs, 1 served as a nonvaccinated contact pig to monitor whether there was spread of vaccinial virus from pig to pig. Vaccinated pigs and nonvaccinated controls were challenged or sham-inoculated 5 weeks later. After challenge, pigs were observed for clinical signs and nasal secretions were tested for virus. On day 5 after challenge, pigs were euthanatized; lungs were examined for gross lesions, and bronchoalveolar lavage specimens were tested for virus replication. Results—A hemagglutination inhibition (...

  • protection of weaned pigs by vaccination with Human Adenovirus 5 recombinant viruses expressing the hemagglutinin and the nucleoprotein of h3n2 swine influenza virus
    Vaccine, 2004
    Co-Authors: Ronald D Wesley, Min Tang, Kelly M Lager
    Abstract:

    Swine influenza virus (SIV), subtype H3N2, is a recent reassortant virus that emerged in 1998 in North American swine causing severe respiratory and reproductive disease. In this study, two replication-defective Adenovirus recombinants were developed as potential vaccines against H3N2 influenza viruses. Three groups of 3-week-old pigs (10 pigs per group) were vaccinated intramuscularly (IM) with the recombinants; one group was vaccinated with the recombinant Adenovirus expressing the influenza virus H3 hemagglutinin (HA) protein, one group was vaccinated with the recombinant Adenovirus expressing the nucleoprotein (NP), and one group was vaccinated with both recombinants in a mixture. Two additional control groups (10 pigs per group) were included in the animal trial. One control group was challenged with a virulent H3N2 field strain and one control group remained unchallenged. The results showed that pigs in the groups given the recombinant Adenovirus expressing HA alone and HA plus NP developed high levels of virus-specific hemagglutination-inhibition (HI) antibody by 4 weeks post vaccination. Pigs in the group vaccinated with both recombinant viruses in a mixture were completely protected. Complete protection was shown by the lack of nasal shedding of virus following challenge and by the lack of lung lesions at 1 week following the challenge infection. Thus, replication-incompetent Adenovirus vaccines given simultaneously to pigs are efficacious for SIV and have the additional advantage over commercial vaccines that suckling piglets have no pre-existing maternally-derived antibody to block early life vaccination.