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Virus and bioinformatics articles with some microbiology and immunology thrown in for good measure
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Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses

Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses | Virology and Bioinformatics from Virology.ca | Scoop.it

Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent clinical phenotype seen in human LAIV inoculation.

 

Ed Rybicki's insight:

Well, of course they do: they engage ALL the levers making the immune system work!

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Plant-produced virus-like particle vaccines

Virus-like particles (VLPs) are possibly the best candidates for safe, immunogenic, efficacious and inexpensive vaccines, for both animals and humans. Well-characterized human and animal viruses such as hepatitis B and C, HIV and papillomaviruses, rotaviruses, norovirus, foot-and-mouth disease viruses and even influenza A virus proteins have all been successfully investigated for VLP formation. Proteins have been produced in transgenic plants and via transient expression techniques; simple structures and structures depending on more than one protein, naked and enveloped particles, and peptides displayed on other viruses have all been made. There have been multiple proofs of concept, and more than a few proofs of efficacy. This chapter covers the history of VLP production in plants, and explores a few examples in detail to illustrate the potential of such a mode of production for human and animal medicine.


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Ed Rybicki's curator insight, February 4, 2:12 AM

For those of you with brass in pocket...B-)

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Solution to Vaccine Mystery Starts to Crystallize

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More than 80 years ago, manufacturers started spiking vaccines with alum, an additive, termed an adjuvant, that spurs a stronger reaction from the immune system. Yet scientists have struggled to explain exactly how alum, a catch-all term for several types of aluminum-containing adjuvants, does this. Recently, researchers have floated at least three possible mechanisms, including one that involves DNA spilled from dying cells. The reason alum works so well, several studies suggest, is that it trips an alarm that alerts the immune system when cells are in trouble. Insights into how alum works might allow researchers to design replacements that retain alum's advantages but lose some of its shortcomings.

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ABC's The View: Just Say No to adding Jenny McCarthy to The View. Petition that supports vaccination.

ABC's The View: Just Say No to adding Jenny McCarthy to The View

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Japanese health ministry withdraws recommendation for HPV vaccine

Japanese health ministry withdraws recommendation for HPV vaccine | Virology and Bioinformatics from Virology.ca | Scoop.it
It’s not been a great year for the HPV vaccine. First we learned that the completion rates in the US remain alarmingly low, and now the Japanese health ministry
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Rising measles outbreaks threaten vaccine-averse

Rising measles outbreaks threaten vaccine-averse | Virology and Bioinformatics from Virology.ca | Scoop.it

Seven confirmed cases of measles in Toronto, Ontario, so far this year, for a total of 12 in Canada to date, are prompting public health officials to remind doctors that the once-common childhood illness risks establishing a foothold again.

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Ed Rybicki's curator insight, May 6, 2013 1:23 PM

And why?  Because risk-averse parents aren't vaccinating their children against the things THEY were vaccinated against, which means we're back in the 1950s again as far as morbidity / mortality figures are concerned.

 

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Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000 (®) compared with Dryvax (®).

Background: Routine vaccination against smallpox (variola) ceased in the US in 1976. However, in 2002 limited coverage for military personnel and some healthcare workers was reinstituted. In March 2008, ACAM2000® replaced Dryvax® as the vaccine used in the United States against smallpox. Unintentional transfer of vaccinia virus from a vaccination site by autoinoculation or contact transmission, can have significant public health implications. We summarize unintentional virus transfer AEs associated with ACAM2000® since March 2008 and compare with Dryvax®.

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Virus-like particles produced in plants as potential vaccines

Virus-like particles produced in plants as potential vaccines | Virology and Bioinformatics from Virology.ca | Scoop.it

Virus-like particles (VLPs) have been produced as candidate vaccines in plants virtually since the introduction of biofarming. Even today, VLPs remain the best candidates for safe, immunogenic, efficacious and inexpensive vaccines. Well-characterized human animal viruses such as HBV, HCV, HIV and HPV, rotaviruses, norovirus, foot and mouth disease viruses and even influenza virus proteins have all been successfully investigated for VLP formation. Proteins have been produced in transgenic plants and via transient expression techniques; simple structures, structures depending on more than one protein, naked and enveloped particles have all been made. There have been multiple proofs of concept, more than a few proofs of efficacy, and several products moved into human trials. This review will cover the history of VLP production in plants, and will explore a few examples in detail to illustrate the potential of such a mode of production for human and animal medicine.

 Image of HIV-1 Pr55Gag VLPs produced in plants, courtesy of Ann Jaffray, UCT.  Bar = 100 nm


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Ed Rybicki's curator insight, April 2, 2013 12:44 AM

OK, yes, blowing my own trumpet...but it will put the recent news of FMDV VLPs in perspective, AND point up the fact that these can be (and probably have been) produced in plants - as well as other even more complicated particles, like human rotavirus and bluetongue virus.

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The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating

The Enterovirus 71 A-particle Forms a Gateway to Allow Genome Release: A CryoEM Study of Picornavirus Uncoating | Virology and Bioinformatics from Virology.ca | Scoop.it

In a picornavirus capsid structural integrity must not be compromised until a key mechanism triggers genome release into a permissive cell. It has long been established that the majority of members of the picornavirus family solve this dilemma with a two-step uncoating process initiated by receptor recognition. For human enteroviruses, binding of an entry receptor triggers a series of conformational changes, resulting in an “A-particle” that is primed for genome release. After endocytosis, an unknown trigger causes the A-particle to expel the viral genome, leaving behind an emptied capsid. This process can be mimicked in solution by heating mature virus. Though the capsid species for both of these steps have been isolated, the fine details of the uncoating process have yet to be elucidated. Cryo-electron microscopy reconstructions of the enterovirus 71 A-particle and empty capsid provide compelling structural evidence to suggest that the icosahedral two-fold axis opens a channel that acts as a gateway in the viral capsid, regulating the release of genomic material from the altered particle.

 

Ed Rybicki's insight:

I do SO love good structural virology.

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rabies vaccine

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

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In J Virol.

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JENNIFER LOPEZ FIGHTING PERTUSSIS. GET THE VACCINE FOR YOU AND YOUR BABY. Important, see the video - click HERE.

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Powerful ad for vaccines.

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Oh, Go Get a Fucking Flu Shot Already!

Oh, Go Get a Fucking Flu Shot Already! | Virology and Bioinformatics from Virology.ca | Scoop.it
Hey, dum-dums! It's flu time again! Epidemic o'clock! Let's all get shots and not die and not kill the elderly and infect delicate babies with our germs, shall we?
Chris Upton + helpers's insight:

Sometimes, you've just got to say it....

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Ed Rybicki's comment, January 17, 2013 1:50 PM
Amen! Says he, who is in flu-infested North America without having been vaccinated. Idiot...!
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Lessons from vaccine history : Nature Medicine : Nature Publishing Group

In spite of years of effort, we still lack highly efficacious vaccines against HIV, tuberculosis, malaria and numerous other widespread pathogens.
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Constructing Vaccines [HD Animation] - YouTube

See an organised list of all the animations: http://doctorprodigious.wordpress.com/hd-animations/
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The Unbelievable Impact of Vaccines

The Unbelievable Impact of Vaccines | Virology and Bioinformatics from Virology.ca | Scoop.it
“With the exception of safe water, no other modality, not even antibiotics, has had such a major effect on mortality reduction,” declared the WHO and UNICEF

Via Ed Rybicki
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Not unbelievable...   actually BELIEVABLE!!

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Ed Rybicki's curator insight, August 29, 2013 3:24 AM

SUPERB infographic!!  Share it!  Send it to denialist relatives and friends!!

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PLOS Pathogens: Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines

PLOS Pathogens: Mutated and Bacteriophage T4 Nanoparticle Arrayed F1-V Immunogens from Yersinia pestis as Next Generation Plague Vaccines | Virology and Bioinformatics from Virology.ca | Scoop.it
Abstract

Pneumonic plague is a highly virulent infectious disease with 100% mortality rate, and its causative organism Yersinia pestis poses a serious threat for deliberate use as a bioterror agent. Currently, there is no FDA approved vaccine against plague. The polymeric bacterial capsular protein F1, a key component of the currently tested bivalent subunit vaccine consisting, in addition, of low calcium response V antigen, has high propensity to aggregate, thus affecting its purification and vaccine efficacy. We used two basic approaches, structure-based immunogen design and phage T4 nanoparticle delivery, to construct new plague vaccines that provided complete protection against pneumonic plague...

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Medicago successfully produces plant-based Rotavirus VLP vaccine candidate

Medicago successfully produces plant-based Rotavirus VLP vaccine candidate | Virology and Bioinformatics from Virology.ca | Scoop.it

Medicago Inc., a biopharmaceutical company focused on developing highly effective and competitive vaccines based on proprietary manufacturing technologies and Virus-Like Particles (VLPs), today announced the successful production of a Rotavirus VLP vaccine candidate comprising all four structural antigens of rotavirus (VP2, VP4, VP6 and VP7) using Medicago's plant-based manufacturing platform.

Medicago also announced today that an international patent application under the Patent Cooperation Treaty (PCT) that broadly covers plant-produced Rotavirus VLPs has been filed.

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Ed Rybicki's curator insight, June 25, 2013 7:38 AM

Going green: how very sensible!

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Evolutionary Dynamics of West Nile Virus in the United States, 1999–2011

Evolutionary Dynamics of West Nile Virus in the United States, 1999–2011 | Virology and Bioinformatics from Virology.ca | Scoop.it

West Nile Virus (WNV) is a mosquito-borne virus of African origin that is widespread around the world. The WNV life-cycle involves mosquitoes and birds, but humans and other animals can be infected, although they are not considered to be important players in the transmission cycle. Clinically, most WNV infections are unapparent, but the virus can disseminate to the central nervous system causing a potentially fatal neurological disease, especially in susceptible populations including elderly and immunocompromised individuals. West Nile virus can also be transmitted by organ transplant and by transfusion of blood and blood components. Like other arboviruses, WNV has the extraordinary capacity of growing in the different microenvironments represented by the invertebrate vector and the vertebrate hosts. From an evolutionary standpoint, the arrival of WNV in the US in 1999 represents a unique opportunity to explore the processes involved in the adaptation and dissemination of an arbovirus in a naïve environment. From the study of WNV sequences, we can not only learn about the evolutionary mechanisms that govern arboviruses, but also update diagnostic tests that rely on the detection of the viral genome upon the occurrence of mutations and study the existence of genetic markers that may be responsible for increases in clinical cases and their severity.

 

 West Nile virus graphic from Russell Kightley Media

Ed Rybicki's insight:

The introduction of WNV into the USA was an inadvertent happening, but analysis of how it has spread and changed since 1999 is a very valuable addition to knowledge.

Now for a vaccine!

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Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly-protective stalk-specific antibodies... J Virol. 2013

We report structural characterization of the first antibody identified to cross-neutralize multiple subtypes of influenza A viruses. The crystal structure of mouse antibody C179 bound to the pandemic 1957 H2N2 hemagglutinin (HA) reveals that it targets a similar epitope on the HA stem as the recently identified human broadly neutralizing antibodies (bnAbs). C179 also inhibits the low-pH conformational change of the HA, but uses a different angle of approach and both heavy and light chains.

  
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An open letter to my dad on the occasion of his recent anti-vax Facebook postings

An open letter to my dad on the occasion of his recent anti-vax Facebook postings | Virology and Bioinformatics from Virology.ca | Scoop.it
Dear Pa, I know you care deeply about many issues, especially social justice.
Chris Upton + helpers's insight:

From  @aetiology   Tara Smith's Blog

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Pedro Fernandes's curator insight, April 4, 2013 12:31 AM

A very didactical letter about a serious problem: the propagation of "noise" in science, worsened by popularised news sharing causes a panic over false (falsified) results. This is a socuial problem that pushed o lot of people to stop vaccinating their children, a mistake that is causing child death, new surges of disease, etc.

 

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Nigeria to Begin Vaccine Production?

Nigeria to Begin Vaccine Production? | Virology and Bioinformatics from Virology.ca | Scoop.it

The Director General of National Agency for Food and Drug Administration and Control, NAFDAC, Dr. Paul Orhii, yesterday, said the country was set to begin local production of routine immunisation vaccines for tuberculosis, hepatitis B, diphtheria, tetanus and pertussis/whooping cough (DPT), polio, measles and yellow fever.

At present, Nigeria depends 100 per cent on United Nation Children's Fund, UNICEF, for vaccine supplies, which according to the Federal Ministry of Health, stands at over N648 billion ($4 billion) annually.

 
Ed Rybicki's insight:

And South Africa produces...how many vaccines, right now?  Down from 14 or so, some 25 years ago?

 

None.  Nil.  Nada.  Zero.  This is a matter for shame.

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The Evolving Field of Human Papillomavirus Receptor Research: A Review of Binding and Entry

The Evolving Field of Human Papillomavirus Receptor Research: A Review of Binding and Entry | Virology and Bioinformatics from Virology.ca | Scoop.it

Human papillomaviruses (HPVs) infect epithelia and can lead to the development of lesions, some of which have malignant potential. HPV type 16 is the most oncogenic genotype and causes various types of cancer, including cervical, anal, and head and neck cancers. However, despite significant research, our understanding of the mechanism by which HPV16 binds to and enters host cells remains fragmented. Over several decades, many HPV receptors and entry pathways have been described. This review puts those studies in context and offers a model of HPV16 binding and entry as a framework for future research. Our model suggests that HPV16 binds to heparin-sulfate proteoglycans (HSPGs) either on the epithelial cell surface or basement membrane through interactions with the L1 major capsid protein. Growth factor receptors may also become activated through HSPGs/growth factor/HPV16 complexes that initiate signaling cascades during early virion-host cell interactions. After binding to HSPGs, the virion undergoes conformational changes leading to isomerization by cyclophilin B and proprotein convertase-mediated L2 minor capsid protein cleavage that increases L2 N-terminus exposure. Along with binding to HSPGs, HPV16 binds to α6 integrins, which initiate further intracellular signaling events. Following these primary binding events, HPV16 binds to a newly identified L2-specific receptor, the annexin A2 heterotetramer. Subsequently, clathrin-, caveolin-, lipid raft-, flotillin-, cholesterol-, dynamin-independent endocytosis of HPV16 occurs.

 Papillomavirus graphic from Russell Kightley Media
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Designing Tomorrow's Vaccines — NEJM

Designing Tomorrow's Vaccines — NEJM | Virology and Bioinformatics from Virology.ca | Scoop.it
Review Article from The New England Journal of Medicine — Designing Tomorrow's Vaccines
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Stop Making Excuses: Why Flu Spike Still Points to Vaccine Benefits

Stop Making Excuses: Why Flu Spike Still Points to Vaccine Benefits | Virology and Bioinformatics from Virology.ca | Scoop.it
For more than a week now, media headlines have warned of a flu epidemic. There have been numerous reports of symptomatic patients flooding emergency rooms and taxing vaccine supplies. Boston and New York State have declared states of emergency.
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Connecting the Dots: Chicken Pox, Varicella Vaccine and Shingles | Vaccinews Blog

Connecting the Dots: Chicken Pox, Varicella Vaccine and Shingles | Vaccinews Blog | Virology and Bioinformatics from Virology.ca | Scoop.it
“How likely is it that my older 2 kids (who got wild pox and weren’t vaccinated) will get shingles later?”

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anarchic_teapot's curator insight, January 13, 2013 11:38 AM

Important stuff. Needs to be read and passed on.