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Sarah Muncy

ScienceDirect.com - Vaccine - Intranasal and intramuscular immunization with Baculoviru... - 0 views

www.sciencedirect.com/...S0264410X10009412

shared by Sarah Muncy on 27 Sep 12 - No Cached
  • An anti-malarial transmission-blocking vaccine (TBV) that prevents fertilization and/or ookinete/oocyst development within the mosquito is an attractive strategy to limit the transmission of malaria
  • The present study used this system to generate a Plasmodium vivax transmission-blocking immunogen (AcNPV-Dual-Pvs25).
  • Plasmodium vivax
  • ...10 more annotations...
  • A variety of expression vectors (e.g., Escherichia coli, Pichia pastoris and DNA) have been used to express Pvs25 protein which has been administered alone or in combination with adjuvants
  • To date these studies suggest that the recombinant protein currently requires both not only linear, but conformation dependent epitopes, and a strong adjuvant to induce transmission-blocking antibodies.
  • Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks Plasmodium vivax transmission
  • Recently, we have developed a new vaccine vector system based on the baculovirus Autographa californica nucleopolyhedrosis virus (AcNPV) termed the “Baculovirus Dual Expression System”, which drives expression of vaccine candidate antigens by a dual promoter that consists of tandemly arranged baculovirus-derived polyhedrin and mammalian-derived CMV promoters. It has been shown that AcNPV, an enveloped double-stranded DNA virus that naturally infects insects, possesses strong adjuvant properties that can activate dendritic cell-mediated innate immunity
  • Mucosal vaccines have several attractive features compared with parenteral vaccines (e.g., safety, cost-effectiveness and ease of administration), but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. We provide evidence that i.n. immunization is a feasible alternative for preventing malaria, which is transmitted through non-mucosal routes
  • These results are consistent with our previous work showing that intranasal immunization with the baculovirus-based vaccine induced strong systemic humoral immune responses with high titres of antigen-specific antibodies and conferred complete protection against malaria blood-stage challenge
  • which can induce immunological memory against heterologous antigens in a rodent model; however, it is precluded from clinical use due to its enterotoxicity and potential hazardous effects on olfactory nerves [22]. In contrast, a baculovirus-based delivery system may offer an attractive immunization method, as AcNPV exhibits low cytotoxicity and is incapable of replication in mammalian cells
  • The data described here adds to previously presented data showing the significant potential of the baculovirus dual expression system against the blood stages of the parasite
  • but also demonstrates clearly its ability to induce antibodies against the ookinete surface protein Pvs25, and to elicit a transmission-blocking immune response against the P. vivax isolates from endemic areas, and a transgenic rodent malaria parasite model in preliminary studies.
  • One was SMFA on peripheral blood from P. vivax infected patients.
  • Sarah Muncy on 27 Sep 12
     
    Reference paper #2. Gave me information on malaria and baculoviruses.
Sarah Muncy

ScienceDirect.com - Vaccine - Hemagglutinin Displayed Baculovirus Protects Against High... - 0 views

www.sciencedirect.com/...S0264410X10011850

shared by Sarah Muncy on 26 Sep 12 - No Cached
    • Sarah Muncy
      Sarah Muncy on 26 Sep 12
       
      So, the baculovirus on TOP of having the H5HA on it, can also get the immune system to kick in better?
  • It is remarkable that low doses (103pfu/mouse) of BVs act as an effective adjuvant [41]. Therefore, reducing BV concentration and elongating vaccination intervals may prevent memory responses to BV administration
  • scanning densitometry
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  • Foreign immunogens or peptides can be displayed on the envelope of AcMNPV by fusion with the baculovirus major envelope protein gp64
  • Baculoviruses have strong adjuvant activity to promote humoral and cellular immune responses against coadministered antigens, activate dendritic cells maturation, induce the production of cytokines, chemokines, and type I IFNs
  • There are two influenza vaccine approaches licensed in the US; the inactivated, split vaccine and the live-attenuated virus vaccine. Inactivated vaccines can efficiently induce humoral immune responses but generally only poor cellular immune responses.
  • Therefore, influenza HA can be displayed on the surface of baculovirus
  • virus-like particle (VLP)
  • Even though cellular immune responses cannot confer sterilizing immunity, they are able to reduce the severity of infection and lower morbidity and mortality rates [47], and antigen-specific memory T cells are able to rapidly respond to a secondary virus infection [45]. Furthermore, cellular immune responses to the conserved epitopes contained in vaccines may provide cross-protective immunity against different subtypes of influenza virus infection
  • To confirm that each HA was incorporated on the envelope of baculoviruses, supernatants from infected Sf9 cells were used to perform hemagglutination assay
  • Most BV display strategies rely on gp64 protein which is the major envelope protein of baculovirus.
  • Sarah Muncy on 26 Sep 12
     
    This paper gave me a better understanding of some aspects of my focal paper that were unclear. How to test for HA, and how baculoviruses may be adjuvants in addition to expression vectors.
Casey Finnerty

Flu Deaths Reach Epidemic Level, but May Be at Peak - NYTimes.com - 0 views

www.nytimes.com/...levels-but-may-be-peaking.html

virology influenza microbiology

shared by Casey Finnerty on 13 Jan 13 - Cached
  • Although the report supported getting flu shots, it said that new vaccines offering lifelong protection against all flu strains, instead of annual partial protection against a mix-and-match set, must be created.
  • “Vaccine effectiveness” is a very different metric from vaccine-virus match, which is done in a lab. Vaccine efficacy is measured by interviewing hundreds of sick or recovering patients who had positive flu tests and asking whether and when they had received shots.
  • During the 2009 swine flu pandemic, many elderly Americans had natural protection, presumably from flus they caught in the 1930s or ’40s.
  • ...12 more annotations...
  • “Think about that,” Dr. Osterholm said. “Even though they were old, they were still protected. We’ve got to figure out how to capture that kind of immunity — which current vaccines do not.”
  • Dr. Bresee acknowledged the difficulties, saying: “If I had the perfect answer as to how to make a better flu vaccine, I’d probably get a Nobel Prize.”
  • a preliminary study rated this year’s vaccine as 62 percent effective, even though it is a good match for the most worrisome virus circulating.
  • urged Americans to keep getting flu shots.
  • Even though deaths stepped — barely — into epidemic territory for the first time last Saturday, the C.D.C. officials expressed no alarm, and said it was possible that new flu infections were peaking in some parts of the country.
  • Epidemiologists count how many death certificates are filed in a flu year, compare the number with normal years, and estimate what percentage were probably flu-related.
  • The C.D.C.’s vaccine effectiveness study bore out the point of view of a report released last year by the University of Minnesota’s Center for Infectious Disease Research and Policy. It said that the shot’s effectiveness had been “overpromoted and overhyped,” said Michael T. Osterholm, the center’s director.
  • At the same time, he praised the C.D.C. for measuring vaccine effectiveness in midseason. “We’re the only ones in the world who have data like that,” he said.
  • “To get a vaccine across the ‘Valley of Death’ is likely to cost $1 billion,”
  • the metric means the shot “reduces by 62 percent your chance of getting a flu so bad that you have to go to a doctor or hospital.”
  • “far from perfect, but by far the best tool we have to prevent influenza.”
  • Most vaccinations given in childhood for threats like measles and diphtheria are 90 percent effective or better. But flu viruses mutate so fast that they must be remade annually.
Sarah Muncy

A Breakthrough Against Leukemia Using Altered T-Cells - NYTimes.com - 1 views

www.nytimes.com/...mia-using-altered-t-cells.html

virology cancer immunology microbiology

shared by Sarah Muncy on 10 Dec 12 - No Cached
  • To perform the treatment, doctors remove millions of the patient’s T-cells — a type of white blood cell — and insert new genes that enable the T-cells to kill cancer cells. The technique employs a disabled form of H.I.V. because it is very good at carrying genetic material into T-cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turn malignant in leukemia.
  • The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells
  • cytokine-release syndrome, or cytokine storm
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  • Dr. June knew that a drug could lower IL-6
  • tocilizumab
  • the altered T-cells persist in the bloodstream
  • The researchers are not entirely sure why the treatment works, or why it sometimes fails.
  • It is not clear whether a patient’s body needs the altered T-cells forever. The cells do have a drawback: they destroy healthy B-cells as well as cancerous ones, leaving patients vulnerable to certain types of infections, so Emma and the other patients need regular treatments with immune globulins to prevent illness.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      I was wondering when they'd get to the consequences of killing off the B cells- that's huge.
  • Sarah Muncy on 12 Dec 12
     
    That's so funny- I just saw the update email and Dr. Finnerty also saw this topic (a different article) and posted it, too!)
Casey Finnerty

Dr. Donald A. Henderson, Who Helped End Smallpox, Dies at 87 - The New York Times - 1 views

www.nytimes.com/...d-end-smallpox-dies-at-87.html

smallpox vaccine

shared by Casey Finnerty on 22 Aug 16 - No Cached
  • Dr. Donald A. Henderson, a leader of one of mankind’s greatest public health triumphs, the eradication of smallpox, died on Friday in Towson, Md. He was 87.
  • died in a hospice of complications of a hip fracture, including infection with antibiotic-resistant staphylococcus, a dangerous pathogen he had himself researched and raised alarms about
  • The last known case was found in a hospital cook in Somalia in 1977.
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  • The only other disease to have been banished from the earth is rinderpest, a little-known relative of measles that kills hoofed animals and once caused widespread starvation in Africa; it was eradicated in 2011.
  • Smallpox, caused by the variola virus, was long one of mankind’s most terrifying scourges.
  • it killed almost a third of its victims, often through pneumonia or brain inflammation.
  • Many others were left blind from corneal ulcerations or severely disfigured by pockmarks.
  • Because it killed 80 percent of the American Indians who caught it, it was a major factor in the European conquest of the New World.
  • In 1796, Dr. Edward Jenner, an English physician, infected a young boy with cowpox taken from a blister on a milkmaid’s hand. Cowpox, a mild disease, protected those who had it from smallpox, and the modern vaccine era began.
  • Dr. Henderson quickly realized that trying to vaccinate vast populations was futile and switched to “ring vaccination.”
  • Dr. Foege, who is considered the father of this tactic, said it was “invented by accident” during a 1967 Nigerian outbreak when he had very little vaccine on hand.
  • “The first night, we asked ourselves what we would do if we were a virus bent on immortality,”
  • In 1977, success in hand, Dr. Henderson became dean of the Johns Hopkins University School of Hygiene and Public Health.“He was an imposing guy — physically big and very confident,” said Dr. Michael J. Klag, the school’s current dean, who was a student in that era. “He did not suffer fools gladly, and you were never sure if you were a fool or not.”
  • He gloomily foresaw failure for most other disease-elimination campaigns. The “siren song of eradication,” he once wrote, had led to goals that were more “evangelical” than attainable.
  • The problem, he would explain, was that each viral foe was so different. Smallpox had many weaknesses to exploit; it had no animal host. Every case can be found because victims have pox on their faces, and one vaccination provides lifetime immunity.
  • In 2011, when Bill Gates threw the full weight of his foundation into fighting polio, he struggled to explain how he would overcome such obstacles and, at the end of an interview, turned to an aide and said aloud, “I’ve got to get my D. A. Henderson response down better.”
  • The campaign, many experts have noted, succeeded just in time. A few years later, the virus that causes AIDS spread across Africa. Because the live smallpox vaccine can grow in an immune-compromised person into a huge, rotting, ultimately fatal lesion, it would have been impossible to deploy it.
Sarah Muncy

Herd immunity: cow virus successfully targeted for extinction | Ars Technica - 1 views

arstechnica.com/...sfully-targeted-for-extinction

shared by Sarah Muncy on 14 Sep 12 - No Cached
    • Sarah Muncy
      Sarah Muncy on 17 Sep 12
       
      I have a hard time feeling glad that an organism (fine, a nucleic acid in a protein capsid that replicates inside hosts and uses their cell machinery to make new component parts) of any kind is gone in the wild. As humans we want to eliminate some parts of nature but not others. Sure there's still these viruses in a lab somewhere, but they are a part of the ecosphere, no? Since we know so little about them, is it wise to think we can eliminate some with no consequences?
Casey Finnerty

Research - A Neuro-Oncology Laboratory at Northwestern University in Chicago - 1 views

www.lesniaklab.com/research.html

virotherapy

shared by Casey Finnerty on 12 Oct 16 - No Cached
  • Most adenoviruses that have been historically used for gene therapy have been based on serotype 5 (AdWT). Unfortunately, expression of the primary receptor for Ad5 (the coxsackie-adenovirus receptor, CAR) is highly variable on cancer cells. In fact, several studies have demonstrated a resistance of malignant glioma to adenoviral vectors, a finding that was subsequently attributed to the quantitative deficiency of CAR on brain tumor cells.
  • First, we tested a variety of tumor specific promoters and identified survivin (S) as an excellent tumor specific promoter for transcriptional control of E1a, a gene essential for CRAd replication (J Neurosurg 104:583, 2006; Cancer Biol Ther 6:679, 2007).
  • Based on the above date data, we then created a novel oncolytic adenoviral vector which utilizes the survivin promoter and binds to heparan sulfate proteoglycans expressed on malignant brain tumors and named this new vector CRAd-S-pk7 (Hum Gene Ther 18:589, 2007).
    • Casey Finnerty
      Casey Finnerty on 12 Oct 16
       
      How specific is the binding/tropism? HS is fairly widespread throughout the body.
  • ...6 more annotations...
  • Second, we have identified several receptors that are over-expressed on brain tumor cells and created a series of pseudotyped Ad5 vectors that recognize these receptors
  • Our studies with CRAd-S-pk7 indicate that the virus provides the highest level of viral replication and tumor oncolysis in glioma cell lines. At the same time, we observed minimal viral replication and toxicity in normal human brain. Injection of CRAd-S-pk7 inhibited xenograft brain tumor growth by more than 300%.
  • We were the first group in the country to show that human mesenchymal stem cells can be effectively loaded with a replication competent virus and effectively deliver it to an experimental glioma model
  • When oncolytic vectors are loaded onto stem cells, the virus effectively "hides" from the immune system for an extended period of time. The ability of stem cells to suppress the anti-viral immune response in a permissive and tumor-bearing animal model is the subject of one of our latest manuscript
  • Finally, to further enhance the therapeutic efficacy of stem cells, we have optimized them to specifically traffic to intracranial tumors via genetic modification with single-chain antibodies against antigens expressed on gliomas
  • Our latest work in this area supports the development of neural stem cell based cell carriers for oncolytic virotherapy
Haram LEE

BMC Cancer | Full text | Oncolytic Targeting of Androgen-sensitive Prostate Tumor by th... - 4 views

www.biomedcentral.com/...43

vriology Oncolytic virotherapy RSV

shared by Haram LEE on 27 Sep 12 - No Cached
Trevor F liked it
  • Haram LEE on 27 Sep 12
     
    Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells.
  • ...2 more comments...
  • Haram LEE on 27 Sep 12
     
    Is there any other virus can using for Oncolytic virotherapy? - Oncolytic viruses identified to date are: adenovirus, reovirus, herpes simplex virus (HSV), Newcastle disease virus (NDV), vaccinia virus, myxoma virus, influenza virus, measles virus, coxsackievirus and vesicular stomatitis virus (VSV) (Anticancer oncolytic activity of respiratory syncytial virus., http://www.ncbi.nlm.nih.gov/pubmed?term=Anti-cancer%20oncolytic%20activity%20of%20respiratory%20syncytial%20virus)
  • Haram LEE on 27 Sep 12
     
    Why also using xenograft, not only for cell-culture method? - A human prostate tumor xenograft model (30) was used to examine the oncolytic function of RSV in vivo (Figure 2). -We also investigated the efficacy of intraperitoneally (I.P) delivered RSV for causing tumor regression and determined that intraperitoneally injected RSV also rendered significant reduction in the tumor growth compared to the growth of control, medium-treated tumors (Figure 2c). The significant tumor regression by intraperitoneally delivered RSV is shown in Figure 2d. Similar results were obtained with tumors grown in the dorsal flank (Supplementary Figure S2). Therefore, the RSV-responsive restriction of tumor growth at two sites (ear and flank) demonstrates the versatility of RSV in conferring oncolysis in vivo at different anatomical regions. (Anticancer oncolytic activity of respiratory syncytial virus., http://www.ncbi.nlm.nih.gov/pubmed?term=Anti-cancer%20oncolytic%20activity%20of%20respiratory%20syncytial%20virus)
  • Haram LEE on 27 Sep 12
     
    How Oncolytic virus control the inflammation? - Oncolytic virus treatment induced at least a twofold increase or decrease in the expression of 50 genes relative to expression in the PBS-treated tumors (Supplementary Table 1, available online). Of these 50 genes, 48 displayed an increase in expression in the oncolytic virus - treated tumors compared with the controltreated tumors, suggesting that oncolytic virus treatment induced an inflammatory response - To confirm the role of the immune response in oncolytic virus - induced vascular hyperpermeability, we evaluated changes in oncolytic virus - induced vascular leakage in tumor-bearing rats that had been treated with cyclophosphamide before oncolytic virus injection. In addition to its immunosuppressive effects, cyclophosphamide blocks infl ammation and reduces viral clearance, both of which increase the propagation of oncolytic viruses, thereby enhancing therapeutic effi cacy of oncolytic viruses. (Effect of Tumor Microenvironment Modulation on the Efficacy of Oncolytic Virus Therapy, http://www.ncbi.nlm.nih.gov/pubmed?term=Effect%20of%20Tumor%20Microenvironment%20Modulation%20on%20the%20Efficacy%20of%20Oncolytic%20Virus%20Therapy)
  • Haram LEE on 27 Sep 12
Sarah Muncy

Koala pandemic genetics: Viruses have inserted themselves into the human genome 31 time... - 1 views

www.slate.com/...themselves_into_the_human.html

shared by Sarah Muncy on 07 Dec 12 - No Cached
  • And in future generations, those genes will gradually mutate and lose their ability to make new viruses. Eventually, the koala retrovirus will become extinct. All that will remain will be its imprisoned DNA.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Wow- they seem pretty confident in what will happen, what mutations will take place and what their effects will be. Hmm.
  • In many koalas, the virus’ genes aren’t present just in the immune cells. The koalas carry the virus genes in every cell of their bodies, from their vestigial tails to their snub noses and in every organ in between
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Wait, so if the virus can infect EVERY kind of cell, it must either have lots of receptors or a wide range of receptor specificity, right? If it's THAT much of a generalist, then surely it must be infectious to other organisms- or at least capable of entry. Does that mean it's at risk for spread in other mammals?
  • Koalas had long been known to have terrible health
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      I've never heard of a wild animal population having "terrible health." That's something you hear about in pure-bred populations, such as with pure bred dogs. If they have notoriously poor health, why do they exist?
Sarah Muncy

The HIV Virus: A Possible Cure for Leukemia? | Yahoo! Health - 0 views

health.yahoo.net/...v-virus-possible-cure-leukemia

shared by Sarah Muncy on 12 Dec 12 - No Cached
  • It's important to note that the T-cells are removed from the patient before being bioengineered with the HIV virus
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Why is it important to note that the disabled virus isn't injected into the patient? It's function isn't like chemotherapy at all- why even make the comparison?
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Is there some reason they use T cells only? Are they trying to target T cells, but not dendritic cells or macrophages?
  • therapies that involve the reprogramming of a patient’s immune system, may also eventually be used to fight cancerous breast and prostate tumors.
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      What about lupus, or even allergies for that matter?
  • ...1 more annotation...
  • Within hours
    • Sarah Muncy
      Sarah Muncy on 12 Dec 12
       
      Within hours?!
  • Sarah Muncy on 12 Dec 12
     
    Whoa. If someone is doing HIV- this may be helpful. The virus is being used as a delivery device for genetics to reprogram lymphocytes. They're like biological nanorobots.
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