mutation

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Novel flu vaccine shows promise in mice
[Published: 05 June 2003 Source: Anti-Infective Drug News]

A new prototype vaccine developed by researchers at the Wistar Institute might be able to protect recipients not only against this year's strains of the virus, but also against those yet to come, possibly eliminating the need for an annual treatment. A report on the new findings appears in the 2nd June issue of Vaccine (2003;21:2616-2626).

Current flu vaccines trigger an immune response to a pair of prominent viral-coat proteins that mutate constantly, which is why last year's flu vaccine is ineffective against this year's flu strains. The experimental vaccine contains an engineered peptide that mimics a third, smaller viral-coat protein, called M2, that remains largely constant from year to year.

Mice vaccinated with the vaccine generated a strong antibody (Ab) response against M2. In fact, the mice generated a more powerful Ab response to the vaccine than to infections by the flu virus itself. The experimental vaccine was administered twice intranasally to mice. After vaccination, a steep rise in M2-specific Abs was seen in blood samples from the mice, and the mice exhibited significant resistance to viral replication in the respiratory tract.

The researchers are also looking into whether the M2 element of the virus might begin to mutate in the presence of the anti-M2 Abs generated by the new vaccine. Their concern is that the observed viral stability in the M2 region of the flu virus may simply be a reflection of the fact that the immune system does not mount a vigorous response to it, so that evolutionary pressure on that region of the virus is not great.

Source: Anti-Infective Drug News, copyright Espicom Business Intelligence

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The Electric New Paper :
Earlier bird flu vaccine 'causes new strain'
SCIENTISTS have discovered a new strain of bird flu that appears to sidestep current vaccines.
01 November 2006
SCIENTISTS have discovered a new strain of bird flu that appears to sidestep current vaccines. And ironically, it may have been a vaccine that was used to protect poultry from earlier types of the H5N1 flu that led to the virus' evolution. The new variant has become the primary version of bird flu in several provinces of China and has spread to Hong Kong, Laos, Malaysia and Thailand, according to a report published in the latest issue of Proceedings Of The National Academy Of Sciences. It is being called H5N1 Fujian-like, to distinguish it from earlier Hong Kong and Vietnam variants.

'We don't know what is driving this,' report co-author Dr Robert G Webster of St Jude's Children's Research Hospital in Memphis, Tennessee, said. While the new virus has infected people, there is no evidence that it can pass easily from person to person, he said. However, he added that 'this virus is continuing to drift' and that new vaccines will have to be developed. Dr Michael L Perdue, of the World Health Organisation's (WHO) Global Influenza Program in Zurich, Switzerland, said the new variant doesn't indicate any increased risk for people 'other than the fact it seems to be pretty widespread'.

The virus is continuing to change, he added.

Dr Perdue said WHO is working with the Chinese Ministry of Health to develop a vaccine for the new form of the virus.
- AP.

Mutated cold virus kills 10 in U.S., reports CDC

Updated Fri. Nov. 16 2007 4:59 PM ET

CTV.ca News Staff

A mutated version of an adenovirus, a common family of viruses that normally causes simple infections, has caused severe respiratory illness in patients of all ages, including healthy young adults, say U.S. health officials.

The new and virulent strain of adenovirus serotype 14 (Ad14) killed 10 people in parts of the United States earlier this year, mostly from severe pneumonia. It also put dozens into hospitals, the U.S. Centers for Disease Control and Prevention reported in its Morbidity and Mortality Weekly Report on Thursday.

It also caused at least 140 illnesses in outbreaks in New York, Oregon, Washington and Texas. More than 50 of those patients were hospitalized, including 24 who were admitted to intensive care units.

Two of the 10 people who died from the new strain were infants. One was a 19-year-old female recruit at Lackland Air Force Base in Texas, where more than 100 other cases were found.

Most of the patients began their illnesses with symptoms of cough, fever or shortness of breath, which then developed into pneumonia.

"The cases described in this report are unusual because they suggest the emergence of a new and virulent Ad14 variant that has spread within the United States," according to the CDC report.

The cases occurred in 2006 and the first half of 2007; yet no cases have emerged since the spring.

What that means isn't clear, officials admitted.

"The fact that we haven't seen it and detected AD14 does not mean it's not circulating," Dr. Larry Anderson, director of the division of viral diseases in the national centre for immunization and respiratory diseases, said during a teleconference Thursday.

"I think it does mean, though, that it's not causing major clusters that present themselves as a public health threat."

No cases found in Canada

The Public Health Agency of Canada alerted health professionals in late April to the fact that clusters of disease caused by this new strain had been reported in the United States.

"Since we sent that note to physicians back in April, no outbreaks or cases of severe respiratory illness associated with adenovirus type 14 have been reported to the Public Health Agency of Canada," spokesperson Alain Desroches said in an email to CTV News.

CDC officials don't consider the mutation to be a cause for alarm for most people, and they're not recommending any new precautions for the general public.

"It's not a broad public health threat that we're seeing at this time,'' said Anderson.

There are more than 50 types of adenoviruses that can cause human illnesses. They are one cause of the common cold, and can also trigger pneumonia and bronchitis.

Dr. Neil Rau, an infectious disease specialist, says the fact the first cases occurred as long ago as May 2006 and we haven't seen more cases, is positive news.

"If it had been very easily transmitted person to person, we would have seen many, many more cases. And it would have spread to many more states and countries," Rau told CTV Newsnet in Toronto on Friday.

The concern, he said, is there is no treatment thus far and experts still don't know how the virus is spread. The CDC report is reassuring, however, in that health care workers who caught the virus did not get very sick.

"So it's not axiomatic that you are going to get really, really sick, unlike SARS, which seemed to have that effect," he said.

The viruses can also cause other illnesses, including pink eye, bladder infections and rashes. Colds caused by adenoviruses can be very severe in the very young and the very old as well as in certain other people, like those with compromised immune systems.

Yet other people infected with adenoviruses don't suffer symptoms at all, or simply come down with a common cold.

The Ad14 form of adenovirus was first identified in 1955. In 1969, it was blamed for a rash of illnesses in military recruits stationed in Europe. It's been detected rarely since then, but seems to growing more common.

There are no licensed medications for adenoviruses. Patients usually are treated with liquids, bed rest and pain relievers.

Mutated from this vaccine maybe?

CDC: New Respiratory Bug Has Killed 10

By MIKE STOBBE – 1 hour ago

ATLANTA (AP) — A mutated version of a common cold virus has caused 10 deaths in the last 18 months, U.S. health officials said Thursday. Adenoviruses usually cause respiratory infections that aren't considered lethal. But a new variant has caused at least 140 illnesses in New York, Oregon, Washington and Texas, according to a report issued Thursday by the U.S. Centers for Disease Control and Prevention.

CDC officials don't consider the mutation to be a cause for alarm for most people, and they're not recommending any new precautions for the general public.

"It's an uncommon infection," said Dr. Larry Anderson, a CDC epidemiologist.

The illness made headlines in Texas earlier this year, when a so-called boot camp flu sickened hundreds at Lackland Air Force Base in San Antonio. The most serious cases were blamed on the emerging virus and one 19-year-old trainee died. "What really got people's attention is these are healthy young adults landing in the hospital and, in some cases, the ICU," said Dr. John Su, an infectious diseases investigator with the CDC.

There are more than 50 distinct types of adenoviruses tied to human illnesses. They are one cause of the common cold, and also trigger pneumonia and bronchitis. Severe illnesses are more likely in people with weaker immune systems. Some adenoviruses have also been blamed for gastroenteritis, conjunctivitis and cystitis. There are no good antiviral medications for adenoviruses. Patients usually are treated with aspirin, liquids and bed rest.

Some people who get infected by the new bug probably would not suffer symptoms, and some may just feel a common cold. Sick people should see a doctor if they suffer a high fever or have trouble breathing, Anderson said. In the CDC report, the earliest case of the mutated virus was found in an infant girl in New York City, who died last year. The child seemed healthy right after birth, but then became dehydrated and lost appetite. She died 12 days after she was born.

Tests found that she been infected with a form of adenovirus, called Ad14, but with some little differences, Su said. It's not clear how the changes made it more lethal, said Linda Gooding, an Emory University researcher who specializes in adenoviruses. Earlier this year, hundreds of trainees at Lackland became ill with respiratory infections. Tests showed a variety of adenoviruses in the trainees, but at least 106 — and probably more — had the mutated form of Ad14, including five who ended up in an intensive care unit

In April, Oregon health officials learned of a cluster of cases at a Portland-area hospital. They ultimately counted 31 cases, including seven who died with severe pneumonia. The next month, Washington state officials reported four hospitalized patients had the same mutated virus. One, who also had AIDS, died.

The Ad14 form of adenovirus was first identified in 1955. In 1969, it was blamed for a rash of illnesses in military recruits stationed in Europe, but it's been detected rarely since then. But it seems to growing more common. The strain accounted for 6 percent of adenovirus samples collected in 22 medical facilities in 2006, while none was seen the previous two years, according to a study published this month in the medical journal Clinical Infectious Diseases.

The new bug could have implications for the military. Other forms of adenoviruses have been a common cause of illness in recruits. Military officials are bringing back an adenovirus vaccine — administered as a pill — that was given to recruits from 1971 to 1999, CDC officials said.

A Barr Pharmaceuticals vaccine for the military, currently being tested, is expected to be licensed in 2009. Like the old pill, it focuses on adenovirus serotypes 4 and 7, because those bugs have been persistent problems, said Col. Art Brown, an Army physician involved in the product's development.

Some CDC officials said a vaccination against the mutant Ad14 might be needed. Brown said it isn't clear if the mutant Ad14 will be an enduring threat, but the military will monitor illness reports. "If it persists, then we'd consider if the vaccine needs to be modified further," said Brown, of the U.S. Army Medical Materiel Development Activity.

Or this vaccine?

Vaccine failure, cause unclear
Last updated: Tuesday, November 13, 2007
An experimental Aids vaccine used in a recent trial may have placed participants at higher risk of infection with HIV - although whether or not that was truly the case remains unclear. What is clear is the concern among experts that the news will keep would-be trial participants away from future Aids vaccine studies. "That's always a possibility and that's the reason why we have to be very transparent and open and honest, and be very energetic to educate people to understand just what went on here," said Dr Anthony Fauci, an Aids research pioneer and director of the US National Institute of Allergy and Infectious Diseases (NIAID). The institute was a partner in the trial. "Already we have a lot of people misinterpreting that the vaccine itself actually gave recipients HIV infection - that's impossible," he said. "We have a lot of education to do and there's always a danger that this could sour people on getting involved in vaccine trials." Experiment's results could give wrong impression Another expert agreed that the collapse of the large, phase II trial of Merck & Co.'s V520 vaccine could send the wrong message. "It's a blow to the HIV prevention field," said Rowena Johnston, vice president of research at the Foundation for Aids Research (amfAR) in New York City. "Clearly, we want to be very careful that people aren't thinking that Aids researchers are going to be putting them at risk." The V520 vaccine was the first of the so-called "viral vector" HIV vaccines to make it all the way to such a large, phase II trial, after showing much promise in smaller, earlier studies. What the research involved The vaccine used a harmless adenovirus - a type of cold virus - as a "vector" to deliver a set of three synthetically derived HIV genes. The hope was those genes would help prime the immune system against the virus that causes Aids. The virus vector approach is a common one in vaccine research generally, and HIV/Aids experts had high hopes for the Merck vaccine, which was meant to be tested in more than 3 000 volunteers uninfected with HIV. Unfortunately, the vaccine failed to deliver. In September, a preliminary analysis of the data showed no statistical difference between those who got the shot and those who got a placebo, in terms of new infections. The trial was halted at that time. Reporting at a scientific meeting in Seattle, the research team said an updated review of the numbers had since revealed a widening gap in infections that actually favoured the placebo. What the research revealed So far, the researchers said, 49 of 914 men vaccinated have tested positive for HIV, compared to 33 of 922 men who got the placebo shot. And in a puzzling twist, individuals who had higher levels of pre-existing immunity to the adenovirus before vaccination were actually much more prone to developing HIV infection, compared to participants with low levels of immunity, the researchers said. Among 778 male volunteers with a high level of pre-existing adenovirus immunity, 21 of those vaccinated are now HIV-positive, versus nine in the placebo arm of the trial. In terms of vaccine's effectiveness at slowing progression from HIV infection to Aids, the trial was also a bust. Among participants infected with HIV, researchers have so far seen no difference in "viral load" - HIV levels in the blood - between those who received a shot and those who did not. The vaccine's failure comes as a disappointment to Aids researchers, the experts said. However, the notion that the vaccine actually heightened users' risk for infection is still far from certain, they added. 'Impossible vaccine directly infects with HIV' First of all, the numbers of cases of new infection recorded in the trial simply didn't reach statistical significance, Fauci said. However, the trend "is noticeable enough that you have to pay attention to it," he added. Fauci and Johnston stressed that it's impossible for the vaccine itself to directly infect a person with HIV, because the adenovirus was the only pathogen included in the shot. However, there is the possibility that vaccination might have spurred changes in the immune systems of individuals whose immune systems were already primed to fight the adenovirus. Theoretically, those immune-system changes could have made HIV infection more likely in these people if they were exposed to the virus. Research continuing "HIV replicates much better in immune cells that are activated," Fauci explained. For certain trial participants with a high pre-existing immunity to the adenovirus, vaccination could have put their immune system on a kind of "high alert" - activating exactly the type of CD4+ T-cells that HIV is attracted to, he said. "Those CD4+ T-cells are then going to be very vulnerable targets for HIV when you become exposed to HIV," Fauci theorised. But he also stressed that this only remains a theory. Research is continuing to see if the vaccine did, in fact, leave participants more vulnerable to contracting HIV. "What we are trying to do now is to mine the data to see if we can find out any mechanistic or other circumstantial information that could help us decipher that out, and determine whether this is 'really real,'" Fauci said. That research could take up to a year to yield results, he noted. In the meantime, Fauci and Johnston agreed that vaccine research using viral vectors should continue to go forward, albeit with an added note of caution. Future vaccine trials to be changed If the trend seen in the study is confirmed, it could mean changes in the way the organisers of vaccine trials recruit participants in the future, they said. "If it turns out to be biologically significant, then we will have to be very careful when using a viral vector to which people have underlying immunity, because that could lead to a significant activation of their immune responses," Fauci said. Trial organisers would become more selective as they recruit participants, he said, "to make sure that we don't have people who have underlying immunity to the vector in question." Both experts stressed that trial participants should always do their best to prevent exposure to HIV and not assume that an experimental vaccine gives them added protection. "The counselling that people in trials get is really very thorough," Johnston said, "and yet I think that as trial participants, many people really do come away with the perception that they are being given a product that might protect them." Safe behaviour urged Safe behaviours, especially condom use, remain the surest way to prevent infection with HIV, whether you are in a trial or not, Johnston said. "To protect yourself, you really need to assume that the vaccine won't work, and then keep on protecting yourself in every way possible." In the meantime, an estimated 39 million people remain infected with HIV worldwide, and the hope for a safe, effective vaccine delivered by a viral vector remains high, she said. "The viral vector is really a very good idea, it's still one of the best ideas that's out there," Johnston said. "I don't think the failure of one candidate from one company should signal the end of this as a concept." – (E.J. Mundell/ HealthDay)

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