Posts Tagged ‘Vaccines’

Further delay before the end of smallpox virus?

Friday, May 2nd, 2014

Smallpox vaccine Variola, the virus that causes smallpox, is on the agenda of the upcoming meeting of the World Health Assembly (WHA), the governing body of the World Health Organization. The decision to be made is whether the last known remaining live strains of the virus should be destroyed. An international group of scientists argue in an opinion piece published on May 1st in PLOS Pathogens that the WHA should not choose destruction, because crucial scientific questions remain unanswered and important public health goals unmet.

Smallpox was declared eradicated in 1980, the only human pathogen for which successful eradication has been achieved to date. Since then, limited research focusing on diagnostic, antiviral and vaccine development, under close direction and oversight, has continued in two high-security laboratories – one in Russia and one in the US – the only places that are known still to have live variola strains. The justification for this research is that smallpox might re-appear via intentional release. Indeed, recent advances in synthetic biology make the possibility of re-creating the live virus from scratch more plausible.

Summarizing the focus and the achievements of the research on live variola over the past several decades, the authors of the PLOS Pathogens article mention several new smallpox vaccines (the ones widely used prior to eradication would not meet today’s stricter safety standards for routine use) and two new drug candidates that, based on research so far, appear to be promising antivirals against the virus that causes smallpox. However, both of these drug candidates have not yet been licensed for use against the disease. “Despite these considerable advances, they argue that “the research agenda with live variola virus is not yet finished”.

Are We There Yet? The Smallpox Research Agenda Using Variola Virus. (2014) PLoS Pathog 10(5): e1004108. doi:10.1371/journal.ppat.1004108

Should Remaining Stockpiles of Smallpox Virus Be Destroyed?


Making sense of microbiology

Wednesday, October 30th, 2013

In a discussion on Twitter earlier this week I made an off the cuff remark which turned out to be unexpectedly telling. Discussing online science writing, I said:

We need sense-making, not more coverage.

Later that day I came across this post by Nathalia Holt - The Goldilocks Approach to Vaccines. I was already considering featuring this story in MicrobiologyBytes this week. Now, I feel I don’t need to (as long as you promise to go and read the full story on her blog):

“On Tuesday, Louis Picker began his talk to a packed room at the AIDS Vaccine meeting in Barcelona, Spain with the line, “The trick to making a vaccine is to be humble and accept the fact that viruses are smarter than we are.” He wasn’t referring just to HIV. Instead he was talking about CMV, or cytomegalovirus. CMV is very clever. A member of the herpes virus family, it’s over 200 million years old. This long evolution means that the virus has become adept in surviving within mammals. While the virus is found in roughly 45% of people, it rarely causes disease. Given its benign nature, Picker calls it “a parasite not a pathogen.” With these characteristics, perhaps it’s surprising that no one has attempted to use CMV in vaccines before now. What makes Picker’s approach unique is not how it manipulates HIV. In fact, the parts of HIV used in his vaccine are far from exceptionable. The vaccine uses pieces of an HIV protein called gag, a group of proteins that make up the basic structure of the virus. The gag protein has been a component of many failed vaccine attempts. What makes this vaccine different is not the innards of HIV it contains but instead how these pieces are delivered.”

This is exactly the sort of approach to science writing I had in mind when I mentioned sense-making on Twitter. Nathalia is not an average blogger. She is a talented and very experienced author for who her blog is merely a sideline. I have plenty of academic colleagues who would cringe and quibble at some of the terms Nathalia uses in this post, and the way in which she puts across some of the ideas. In spite of that, this is exactly the sort of approach I was thinking of when I tweeted. And it is exactly what I am trying to do when I write MicrobiologyBytes.

I honour of Nathalia, and all the other great science writers online, you’ll notice that I have changed the tagline at the top of MicrobiologyBytes. No longer does it say “The latest news about microbiology”, although that’s what you’ll get if you follow MicrobiologyBytes on Twitter, Facebook or Google+. The new tagline on the site better reflects what MicrobiologyBytes is about.


Vaccines & Correlates of Immune Protection - AIDS Vaccine 2013

Vaccines & Correlates of Immune Protection – AIDS Vaccine 2013


Dengue Vaccines: Not A Reality Just Yet

Monday, October 7th, 2013

Dengue virus (DV) infections cause undisputedly the most important arthropod-borne viral disease in terms of worldwide prevalence, human suffering, and cost. Worldwide DV infection prevalence in 2010 was between 284 to 528 million cases. Approximately 84% of these cases come from Asia and the Americas, where the cost for emerging economies can be as high as 580 million dollars per year. The need for an efficient vaccine against DV is extreme.

Vaccination has been the most desired strategy for controlling the spread of DV. Neutralizing antibodies directed against mosquito-borne flavivirus envelopes can prevent the development of infectious disease. This has been beautifully illustrated by the development of successful vaccines against other related mosquito-borne flaviviruses with similar structure, specifically the attenuated strain 17D vaccine against yellow fever virus (YFV) and the attenuated strain 14-14-2 against Japanese encephalitis virus (JEV), both obtained by serial passage in cell culture.

Why then has the development of a DV vaccine proven so challenging? Natural DV infection triggers a robust, neutralizing immunity that provides an apparently life-long protection against the infecting DV serotype and a short-lived (months) cross-protection against heterologous DV serotypes. Interestingly, the humoral response to DV not only mediates protection though viral neutralization, but also seems to play a major role in the development of more severe forms of dengue disease. Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) cases are often associated with secondary DV infections with a heterologous DV serotype.

Dengue Vaccines

There are two main windows of opportunity to build upon toward realizing efficient vaccination for DV. First, a clinically relevant animal model for dengue infection and vaccine development is lacking. Rhesus monkeys do not show clinical signs of infection after a wild-type DV challenge; instead the intensity and length of viremia serves as a proxy to infer protection. Second, rigorous correlates of protection have not been established for DV. The best available indicator of immunogenicity is the titration of neutralizing antibodies, however titration of plaque reduction neutralization antibodies has not been promoted to a bona fide correlate of protection because of ambiguous results pertaining to the protective titer. Testing the protection efficiency of tetravalent vaccine candidates in volunteers may answer both questions. Results from the first human DV challenge experiments have been recently published and demonstrate the viability of this approach.

Dengue Vaccines: Strongly Sought but Not a Reality Just Yet. (2013) PLoS Pathog 9(10): e1003551. doi:10.1371/journal.ppat.1003551


What do you think a virus is?

Monday, September 23rd, 2013

Viruses Humans are exposed to viruses everywhere they live, play, and work. Yet people’s beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information.

This study used semi-structured interviews to examine people’s beliefs about viruses, vaccines, and the causes of infectious disease. The authors compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why.

Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers described viral replication in terms of cell division, independent of a host. Interestingly, most students held a mental model for vaccination in which the vaccine directly attacks a virus that is present in the body. The findings have immediate implications for how to communicate about infectious disease to young people.


Expert–novice differences in mental models of viruses, vaccines, and the causes of infectious disease.” Public Understanding of Science (2013) Public Understanding of Science 19 2013 doi: 0963662513496954

HIV thirty years on

Thursday, August 29th, 2013

HIV It has been thirty years since human immunodeficiency virus (HIV) was first identified as the cause of acquired immunodeficiency syndrome (AIDS), a landmark discovery that has led to tremendous progress in understanding and combating infection by this life-threatening retrovirus. The most notable achievement during this time has been the development of antiretroviral therapies that substantially improve the quality and length of life in infected individuals. Nevertheless, to date neither a complete cure nor a protective vaccine have been found, and new infections continue to occur at a rate of 6,850 people per day.

This collection of articles takes stock of where we are now, with a collection of articles that discuss different aspects of HIV infection, the progress made towards eradicating the virus, and the challenges of fundamental science and clinical management that remain.

BioMed Central: HIV thirty years on (2013)

Will we ever have a universal flu vaccine?

Wednesday, June 26th, 2013

Will we ever have a universal flu vaccine

“It takes just two shots of the MMR vaccine to protect a child against measles, mumps and rubella for life. The same is true for polio and hepatitis B, a few injections grant life-long immunity against these viral diseases. By showing samples of the viruses to our immune system, we teach it to store a permanent memory of these enemies and guard against them in perpetuity.

Influenza is a different matter. There is a vaccine, but we have to take it every year. That’s because flu viruses evolve at tremendous speed. They copy themselves with surprising sloppiness, producing thousands of slightly different daughter viruses. If different strains infect the same cell, they can carry out the viral version of sex by mingling their genetic material to make hybrid daughters. And occasionally, entirely new strains that we’ve never encountered before can spill over into humans from animals.”

Read more:

Will we ever have a universal flu vaccine? – Ed Yong

How do you study the pathogenesis of Lassa fever virus? (hint – very, very carefully)

Wednesday, May 29th, 2013

Arenavirus How do you study a virus which is so pathogenic, you are (rightly) not allowed to work with it under normal laboratory conditions? Ideally, you need to see how the whole virus works during infection, but in some cases, and Lasse fever is a good example, that’s not such a good idea…

Lassa virus (LASV), the agent of a severe and often fatal hemorrhagic illness known as Lassa fever (LF), is endemic in West Africa and estimated to infect more than 300,000 individuals yearly, hospitalizing 100,000 and causing 20,000 or more deaths. LASV has entered Europe and America via travelers incubating the virus. As a Category A Select Agent, LASV is also a potential bioterrorism threat. We know that early host immune response to LASV is crucial for survival – infected individuals with high virus titres fail to mount an effective innate/adaptive immune response and invariably die, whereas those with less virus in their blood respond immunologically with a T cell response and survive.

By making recombinants between the highly pathogenic Lassa fever virus and the non-pathogenic (for humans, although mice or not so fortunate) closely related Arenavirus lymphocytic choriomeningitis virus (LCMV), Michael Oldstone and colleagues show how potentially life-saving immune responses to the LASV glycoprotein are generated. In addition, the vigorous antiviral immune response to LASV Gp in the recombinant LCMV/LASV hybrid suggests that this construct might be evaluated as a potential vaccine candidate against LASV infection. Even without that, this recombinant virus will serve as a useful tool for uncovering mechanisms of cell binding, entry, infection and immune subversion initiated by the glycoprotein of LASV in a BSL-2 environment rather than the highly restrictive BSL-4 environment required by work with the wild-type LASV.


Pathogenesis of Lassa fever virus infection: I. Susceptibility of mice to recombinant Lassa Gp/LCMV chimeric virus. Virology. 2013 May 15. pii: S0042-6822(13)00219-5. doi: 10.1016/j.virol.2013.04.010
Lassa virus (LASV) is a BSL-4 restricted agent. To allow study of infection by LASV under BSL-2 conditions, we generated a recombinant virus in which the LASV glycoprotein (Gp) was placed on the backbone of lymphocytic choriomeningitis virus (LCMV) Cl13 nucleoprotein, Z and polymerase genes (rLCMV Cl13/LASV Gp). The recombinant virus displayed high tropism for dendritic cells following in vitro or in vivo infection. Inoculation of immunocompetent adults resulted in an acute infection, generation of virus-specific CD8+ T cells and clearance of the infection. Inoculation of newborn mice with rLCMV Cl13/LASV Gp resulted in a life-long persistent infection. Interestingly, adoptive transfer of rLCMV Cl13/LASV Gp immune memory cells into such persistently infected mice failed to purge virus but, in contrast, cleared virus from mice persistently infected with wt LCMV Cl13.

See also: The Pathogenesis of Lassa Fever



Thursday, May 23rd, 2013

BTV VLPs Bluetongue is a severe disease of ruminants, notably sheep and cattle. The causal agent, the dsRNA Bluetongue virus, is spread by an insect vector and occurs in its vector’s habitat in temperate climates throughout much of the world. BTV is the type member of genus Orbivirus in the family Reoviridae, with 26 known serotypes. When bluetongue first broke out in the United Kingdom in autumn of 2007, the disease was already rapidly spreading throughout continental Europe, causing high mortality rates in sheep and having a detrimental effect on the livestock trade through trade restrictions and loss of stock. The only effective weapon against the disease is control of the spread of BTV through rigorous vaccination programmes. Currently available commercial vaccines are based on both inactivated virus and live, attenuated strains and protect against a single serotype or multiple serotypes when provided as a cocktail. However, the possibility of recombination between the live vaccine strain(s) and wild-type virus in infected animals, leading to the emergence of new infectious strains has motivated efforts to develop safer vaccines.

One approach in the development of an inherently safe vaccine has been the production of Bluetongue virus-like particles (VLPs). BTV has a nonenveloped icosahedral structure, with four main structural proteins (VP3, VP7, VP5 and VP2) arranged in concentric shells around the segmented double-stranded RNA genome and minor structural and nonstructural proteins involved in virus replication. French et al. have shown that these four structural proteins, expressed in insect cells using a baculovirus expression system, assemble into virus-like particles devoid of nucleic acid.

This paper describes plant-based high-level expression of assembled subcore-, core- and virus-like particles of BTV serotype 8. Purified preparations of the VLPs, consisting of all four structural proteins, elicited an immune response in sheep and provided protective immunity against challenge with a South African BTV-8 field isolate. This demonstrates that plant expression provides an economically viable method for producing complex VLPs, such as those of BTV, with the desired biological properties. It represents a significant advance in the use of plant-based systems for the production of complex biopharmaceuticals. The methods employed could also be applied to other situations where the expression of multiple proteins is required, such as the reconstruction of metabolic pathways.


A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. Plant Biotechnol J. 06 May 2013 doi: 10.1111/pbi.12076
Plant expression systems based on nonreplicating virus-based vectors can be used for the simultaneous expression of multiple genes within the same cell. They therefore have great potential for the production of heteromultimeric protein complexes. This work describes the efficient plant-based production and assembly of Bluetongue virus-like particles (VLPs), requiring the simultaneous expression of four distinct proteins in varying amounts. Such particles have the potential to serve as a safe and effective vaccine against Bluetongue virus (BTV), which causes high mortality rates in ruminants and thus has a severe effect on the livestock trade. Here, VLPs produced and assembled in Nicotiana benthamiana using the cowpea mosaic virus-based HyperTrans (CPMV-HT) and associated pEAQ plant transient expression vector system were shown to elicit a strong antibody response in sheep. Furthermore, they provided protective immunity against a challenge with a South African BTV-8 field isolate. The results show that transient expression can be used to produce immunologically relevant complex heteromultimeric structures in plants in a matter of days. The results have implications beyond the realm of veterinary vaccines and could be applied to the production of VLPs for human use or the coexpression of multiple enzymes for the manipulation of metabolic pathways.


10 things you should know about novel coronavirus (MERS-CoV)

Wednesday, May 22nd, 2013


Latest News | W.H.O. Global Alert and Response


1. Coronaviruses are a family of viruses that includes viruses that may cause a range of illnesses in humans, from common cold-type respiratory infections to SARS. Viruses of this family also cause a number of animal diseases.

2. What’s it called again?
Currently being referred to as MERS-CoV or nCoV-2012, this virus has also been called Human Coronavirus-Erasmus Medical Center (hCoV-EMC), and even “Saudi SARS” (it’s not – SARS is a related but different Coronavirus).

3. The first known case of MERS-CoV infection was in a Saudi Arabian man who died in early 2012. This particular strain of coronavirus had not been previously identified in humans. The second confirmed case appeared in early September 2012, involving a 49-year old man in Doha, Qatar who had traveled to Saudi Arabia around the same time that the first case was identified. Currently, at least 40 cases have been confirmed, and 20 of those affected have died. The virus has also been found in Tunisia.

4. Where did it come from?
Bats. (It’s [nearly] always bats.) Bat coronaviruses carried by the genus Pipistrellus that differ from MERS-CoV by as little as 1.8%. The existence of over 50 species of Pipistrellus bats in the Arabian Peninsula suggests that they may be the animal reservoir.

5. Symptoms of MERS-CoV infection include renal failure and severe acute pneumonia, which often result in a fatal outcome. In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells because it uses dipeptidyl peptidase 4 (DPP4, also known as CD26) as a receptor.

6. nCoV can penetrate the bronchial epithelium and evade the innate immune system, signs that it is well-equipped for infecting human cells. This suggests that although MERS-CoV may have jumped from animals to humans very recently, it is as well adapted to infecting the human respiratory tract as other, more familiar human coronaviruses, including the SARS virus and the common cold Coronavirus HCoV-229E.

7. The virus is susceptible to treatment with interferons, immune proteins that have been used successfully to treat other viral diseases, offering a possible method of treatment in the event of a large-scale outbreak.

8. How is it transmitted?
Almost certainly like other respiratory viruses, via aerosol droplets from coughs and sneezes, but possibly also by unwashed hands contaminated with respiratory secretions.

9. Is there a vaccine?
Not yet. It is possible to make vaccines agains Coronaviruses and several SARS vaccines were developed but never put into use because the SARS outbreak died away. It should be possible to make a nCoV vaccine if we need one.

10. Is there any travel advice?
At the moment the World Health Organization says there is no reason to impose any travel restrictions. Travel advice will be kept under review if additional cases occur or when the patterns of transmission become clearer.

11. Are we all going to die?
Probably not. Most of the people who have been infected so far have been older men, often with other medical conditions. The outbreak of Severe Acute Respiratory Syndrome (SARS) in 2003 infected over 8000 people and killed nearly 800 before burning itself out. But SARS didn’t kill us all and it’s unlikely that MERS-CoV will either.


Other things you should know: