'Cool' vaccines

We all know the usefulness of certain thermophiles (I'm looking at you, Taq polymerase), but up here in Canada, with our vast arctic tundra, we should be looking for uses for cold-loving organisms - a resource we're more likely to have in abundance.

A group at the University of Victoria has done just that, using genes psychrophilic bacteria to develop temperature-sensitive vaccines.

One at a time, the team swapped out nine so-called essential genes—involved, for instance, in DNA repair or cell division—in F. novicida for their counterparts from Arctic bacteria, such as Colwellia psychrerythraea, a marine microbe that lives in polar waters and ice. Francisella normally dies at 45˚C; introducing the cold-loving genes lowered that threshold by up to 12˚C, depending on the gene and the species it was borrowed from.

When the researchers injected these altered strains into the relatively cool tails of rats, they found that the microbes reproduced locally but didn't spread to the warmer spleen and lungs, where they would normally replicate as well. The key test was whether the strains could act as vaccines. F. novicida is lethal to mice, but when the researchers injected the temperature-sensitive strains, the animals didn't get sick—and they were protected from an otherwise fatal dose of the unaltered F. novicida given 3 weeks later. [Source]

The idea for a temperature-sensitive vaccine is already out there, with a particular flu vaccine capable of replicating in the throat and nose, but not the lungs. The goal is to create safer live vaccines, but could be put to other uses such as study of dangerous pathogens by creating versions that can't replicate in the warm human body, possibly reducing the need for the strict containment measures to keep researchers safe.

The full research article is available free from PNAS.

Cancer Vaccine Clinical Trials

A clinical trial for a new treatment for ovarian cancer and melanoma is about to begin using a vaccine developed at Cornell University. From the press release:

The melanoma trial is being conducted at New York University Medical Center, while the ovarian cancer vaccine trial is at the Roswell Park Cancer Institute in Buffalo, N.Y. The trials are assessing the safety and the anti-tumor immune response of the so-called NY-ESO-1 recombinant protein cancer vaccine alone and in combination with other agents, according to the Cancer Research Institute (CRI), an organization that has recently given $450,000 to Cornell to support vaccine production at the Bioproduction Facility. The facility is a partnership between the Ludwig Institute for Cancer Research and Cornell.
The goal of these trials is to maximize the body's immune response to the NY-ESO-1 protein.

NY-ESO-1 is an antigen found in normal testis and in various tumours. The peptide vaccine stimulates the immune system against cells expressing the NY-ESO-1 antigen leading to lysis of tumour cells (no word on how it affects 'normal testis'). The vaccine isn't meant to be preventative, but rather to stimulate the body's response against an existing tumour.

Investors keen on cancer vaccine

Reuters is reporting that several brokerages have upgraded the stock of a Seattle company, Dendreon, from 'hold' to 'buy'. The reason? Dendreon is the creator of Provenge, a prostate cancer vaccine expected to get FDA approval sometime late this year.

The reason for the excitement is recent data (presented at the American Urological Association annual meeting) showing a modest improvement in prostate cancer survival rates - a 4.1 month increase, with a 3-year survival rate of 42% compared to 23% for the control group. Oddly, the drug extends survival without shrinking tumours. However, Forbes reports that there is some concern over study design:

Much of the skepticism about Provenge until now has related to the perceived limitations of the 500-person study that Kantoff helped run. It was too small, some experts thought, and had an unusual design in which patients who did not receive Provenge and saw their cancer get worse would receive a frozen-then-thawed version of the vaccine.

This is unusual and may be unprecedented, says Donald Berry, head of biostatistics at the M.D. Anderson Cancer Center. It is possible that this frozen-then-thawed vaccine is actually different from Provenge; if it somehow harmed patients (there's no proof it does), it would actually make Provenge appear more effective. He asks how patients did after their cancer had progressed.

What's cool, though, is that if it works and is approved it will be the first cancer vaccine. The treatment itself is manufactured in part from a person's own antigen presenting cells (APCs, in this case dendritic cells). Patient APCs are extracted and co-cultured with a recombinant fusion protein. The now antigen-loaded APCs are then reinfused where they potentially activate a T-cell response against prostate cancer cells. The full course consists of 3 treatments over 4 weeks with only mild side effects compared to standard chemo treatments.

While the survival increase is quite small, it's encouraging and at least highlights the possibility of this kind of therapy. It would be interesting to know the duration of the immune response. Could this method be used as a preventative measure? How effective would it be against other cancers? (using a different antigen, of course)

Canadian Health Concerns

There have been a couple of items in the news recently regarding Canadian health issues. Both of them have been touched on before (which should come as no surprise - we're visionaries here at the Bayblab).

The first is Listeria which began with an outbreak which left one dead and several others ill and the subsequent product recall and shutdown of the Toronto Maple Leaf production facility. We've tackled Listeria before, and discussed some of the strategies companies use to minimize contamination - mainly sanitary design and proper cleaning. In the US, bacteriophage are also used for Listeria management. In Canada, we have yet to adopt these measures:

[Retired Health Canada microbiologist and food inspector Bill] Riedel said Canada needs a system like one approved in the United States two years ago, in which bacteriophage therapy is used to combat Listeria monocytogenes found in foods. Bacteriophages are viruses that infect and destroy bacteria.

As of Wednesday, the number of deaths caused by the outbreak was 6, with 10 others under investigation. Major fast-food chains McDonalds and Mr. Sub were affected by the recall. I wonder if bacteriophage technology would have prevented this outbreak, and if the death toll and economic impact will accelerate a move towards it.

Second up is the mumps outbreak in western Canada. I've written about disease resurgance before, usually measles. This time it's mumps. Close to 200 cases have been reported in the Chilliwack region of British Columbia - a province that typically sees no more than 5 cases per year (according to CBC.ca).

Of the 191 cases reported so far since the outbreak began in Chilliwack in February, 10 to 20 are still active. Half of the people who have been infected have not been immunized, a quarter have had at least one shot and a quarter do not have vaccination records, Dr. Brodkin said. One person developed meningitis, nine suffered hearing loss and 26 had swollen testicles or ovaries. It is not clear how many of those cases will result in permanent deafness or sterility.

Officials fear that up to two-thirds of cases are going undetected and continue to spread the virus. The outbreak has been linked to religious groups in the area who are opposed to vaccination due to their beliefs.

It's baaaa-aack

A few months ago I wrote about a recent spate of measles cases in North America. After years of low immunization rates, the same thing has been happening in the United Kingdom, to the point where measles is once again endemic after more than a decade of halted spread.

Fourteen years after the local transmission of measles was halted in the United Kingdom (UK), the disease has once again become endemic, according to the Health Protection Agency (HPA), the public health body of England and Wales. In an update on measles cases in its weekly bulletin last week, the agency stated that, as a result of almost a decade of low mumps-measles-rubella (MMR) vaccination coverage across the UK, ‘the number of children susceptible to measles is now sufficient to support the continuous spread of measles’

Current vaccination rates in the UK are well below the 95% desired to maintain herd immunity. Of over 50 lab-confirmed measles cases in Scotland so far this year (there have been 461 in England and Wales), only 2 of them were imported from overseas.

Measles is no longer endemic to Canada and the USA, but remains endemic in many other countries. If the current anti-vaccination movement continues to flourish, how long will it be before it returns to our shores?

[via Respectful Insolence]

Soylent Vaccines are Made Out of People!

Jenny McCarthy, mom-celebre and current pin-up girl for the anti-vaccination movement, is descending on Washington DC today for a 'Green Our Vaccines' rally. There's been some buzz in the skeptical blogosphere about the rally, most notably Orac (of course) with a discussion about the Orwellian nature of the new slogan.

The Green Our Vaccines campaign isn't about making vaccines more environmentally friendly, it's about removing toxins. Anti-vaxers, beginning to realize that their former pet thimerosal isn't a vaccine hazard, have moved to the more nebulous 'toxins' as the real danger of vaccines. Their list:It's easy to pick apart this list (sucrose in vaccines is a toxin?), as some people have done. Some of that list probably isn't even present in more than trace amounts: fetal bovine serum, for example, is a cell culture supplement for growing cells to produce vaccine not an additive to the vaccines, and it's purified out. Anti-vaxers are eager to blur the line between vaccine ingredients and components of vaccine production.

One of the items on the list is human diploid cells (from aborted fetal tissue). Sometimes this is listed simply as aborted fetal tissue. While it's understandable that people might not want to inject themselves with aborted fetal tissue (though, I'm not sure it's necessarily toxic), there are still a couple of problems with that inclusion on the list:

1) Vaccine makers aren't grinding up aborted fetuses and injecting them. Nor are they generating new fetal cell lines from them every time a vaccine is made. The 'human diploid cells (from aborted fetal tissue)' are one of two cell lines derived in the 60s and 70s: WI-38 and MRC-5.

2) These cell lines aren't ingredients. They are used to produce viruses used for vaccines. They are removed during the production process (a simple spin will separate the cells from the virus-rich supernatant, which is then further processed). That needs to be stressed, because it applies to many of the "toxins" on the list: tools used for production of vaccines aren't ingredients.

Of course there is a potential moral objection to the use of aborted fetal cells in production, even if they aren't in the vaccine itself. The Catholic Church, for example, encourages the use of alternative vaccines where they exist and to press pharmaceutical companies to develop such alternatives. However even the Church, which is normally rigid in its stance, allows the use of vaccines derived from fetal cells in the absence of an alternative. This is made clear in their official position: "we find, in such a case, a proportional reason, in order to accept the use of these vaccines in the presence of the danger of favouring the spread of the pathological agent, due to the lack of vaccination of children." They go even further than this with regards to the German measles vaccine, adding

This is particularly true in the case of vaccination against German measles, because of the danger of Congenital Rubella Syndrome. This could occur, causing grave congenital malformations in the foetus, when a pregnant woman enters into contact, even if it is brief, with children who have not been immunized and are carriers of the virus. In this case, the parents who did not accept the vaccination of their own children become responsible for the malformations in question, and for the subsequent abortion of foetuses, when they have been discovered to be malformed.

That having been said, the stand taken by the 'Green Our Vaccines' group does not seem to stem from moral objections, but rather they're clear that it's about the fearful toxins. It seems that they're either unsure of how vaccines are produced or willfully misusing charged words (eg. aborted human fetus) to drum up vaccine opposition.

Soylent green may be made out of people, but vaccines aren't.

Measles

Measles seems to be popping up everywhere these days. In February, 3 children in San Diego were diagnosed with the virus, the first reported outbreak since 1991. This initial outbreak spread to another, followed by another 6 and a quarantine. In March, health authorities in Seattle warned travellers of possible exposure. This past week, a measles warning was made for guests at a wedding in Rockland County, NY and, in a separate case, Nassau County, NY. In Milwaukee, four cases have been recently identified, 3 of them in children under 2 years of age. Twelve other children have been quarantined. In Canada, health officials in Guelph have issued a measles warning after an individual who was diagnosed may have exposed others. And in Toronto, 5 cases have been confirmed in the past 4 weeks.

Measles is a highly contagious virus. Symptoms include fever, cough, runny nose, conjuntivitis and a potentially itchy rash. Complications are common and include pneumonia, encephalitis and corneal scarring. In developed countries, the fatality rate is about 1:1000 in otherwise healthy people.

If only there was some sort of shot to prevent infection.

Quack of the Week: John McCain

To be fair, both Democratic presidential hopefuls seem to be unaware of the science surrounding the issue^* but John McCain is being singled out for the following statement which he made last week:

"It's indisputable that (autism) is on the rise amongst children, the question is what's causing it. And we go back and forth and there's strong evidence that indicates that it's got to do with a preservative in vaccines."

Probably the same kind of 'strong evidence' that there were WMDs in Iraq. But this isn't really about McCain per se - there is no shortage of people who share this stance - it's about the idea that mercury-based preservatives (thimerosal) in vaccines are responsible for a rise in autism.

First of all, is it even true that autism and autism spectrum disorders (ASD) are on the rise? It's possible that what we're seeing is an increase in diagnosis of ASD rather than an increase in the disorders themselves - either due to improved diagnostic tests or changes in the way these disorders are classified. This paper from the journal Pediatrics puts some numbers to that idea and shows that autism diagnoses took an upswing at the same time that diagnoses of mental retardation and learning disability declined suggesting that changes in diagnostics may explain the apparant autism epidemic. Orac at Respectful Insolence blogs about this paper in greater depth.

Regardless of whether autism is actually on the rise or not, it's still important to find out the underlying cause. Are mercury-containing vaccines the culprit? The science says no. A link between thimerosal-containing vaccines is not supported by science. Several studies have been done that show no causal link between mercury in vaccines and autism.

"But still," some will say, "we avoid eating certain fish because of mercury levels, so having it in vaccines makes no sense." First of all, the mercury build-up in fish (methyl-mercury) is different from the form in thimerosal (ethyl-mercury). Ethyl-mercury has a much shorter half life and does not build up in the body the same way. And that's beside the point: in the US thimerosal hasn't been used as a preservative in recommended childhood vaccines since 2001. Yet in the US and other countries that no longer use thimerosal, autism diagnoses continue to rise. This tells us that it's not the mercury, but more likely - as mentioned above - changes in the way autism spectrum disorders are identified.

For those who refuse getting vaccinated "to be on the safe side": Don't. Vaccines are responsible for the eradication of smallpox, near-eradication of polio and a host of other diseases (presumably, this is why anti-vaxers feel they can get away with it - because there's little fear of smallpox, polio and the like). Not receiving these routine childhood vaccinations has real public health implications. It's irresponsible to not have your children vaccinated.

As for John McCain, it's irresponsible for HIM to make such strong claims about a connection between mercury in vaccines and an autism epidemic. He needs to surround himself with better science advisors than that.



^*Clinton says: "I am committed to make investments to find the causes of autism, including possible environmental causes like vaccines. [...] I will ensure that all vaccines are as safe as possible for our children by working to ensure that Thimerosal and mercury are removed from vaccines."

Obama says: "An Obama administration will go where the science and the facts lead us, whether it is about climate change or toxic heavy metals in our environment. [...] I support the removal of thimerosal from all vaccines and work to ensure that Americans have access to vaccines that are mercury free."

(source: Age of Autism)

Some people argue that these viewpoints are worse than the stronger McCain statement.

Lights Out For Merck's HIV Vaccine Program?

Perhaps underscoring ARW's suggestion re the need to explore alternative approaches to dealing with infectious disease, Merck have ended their phase II HIV vaccine trial due to lack of efficacy. This spells the end for their Adenovirus-based vector, the fruits of 20 years of R & D work. At least for the time being, they apparently have no specific plans to continue their HIV vaccine program.

Maybe a vector that induces a more vigorous immune response, such as VSV or vaccinia, will be more successful...and maybe Merck or competitors will be shopping around for new vector platforms in the near future...

HPV vaccine program

A pretty decent article in Macleans on the HPV vaccine. Gardasil is a human papilloma virus vaccine that is scheduled to be part of a massive vaccination program of young girls starting this September. The vaccine targets strains 16 & 18 which account for causing 70 percent of cervical cancer cases. It does a poor job of talking about the percentage of adverse events associated with inoculation (probably exceedingly low), however, it still makes one wonder about whether this is really the health priority that we are being led to believe. It also explains a bit of the politics that surround the approval of this vaccination program. I also hope that the makers of the vaccine, Merck & Co., have learned their lesson with Vioxx. On the scale of a vaccination program even rare problems could have serious financial consequences for the pharma giant.