Boys Town Hospital
You are currently browsing the Vaccinews Blog weblog archives for October, 2012.
Boys Town Hospital
Canadian Paediatric Society
Vaccines work by enhancing the protection the immune system already provides. In the battle against the flu, two sets of immune cells do most of the work.
One set, called B cells, makes antibodies that can latch onto free-floating viruses. Burdened by these antibodies, the viruses cannot enter cells.
Once flu viruses get into cells, the body resorts to a second line of defense. Infected cells gather some of the virus proteins and stick them on their surface. Immune cells known as T cells crawl past, and if their receptors latch onto the virus proteins, they recognize that the cell is infected; the T cells then release molecules that rip open the cells and kill them.
This defense mechanism works fairly well, allowing many people to fight off the virus without ever feeling sick. But it also has a built-in flaw: The immune system has to encounter a particular kind of flu virus to develop an effective response against it.
It takes time for B cells to develop tightfitting antibodies. T cells also need time to adjust their biochemistry to make receptors that can lock quickly onto a particular flu protein. While the immune system educates itself, an unfamiliar flu virus can explode into full-blown disease.
Today’s flu vaccines protect people from the virus by letting them make antibodies in advance. The vaccine contains fragments from the tip of a protein on the surface of the virus, called hemagglutinin. B cells that encounter the vaccine fragments learn how to make antibodies against them. When vaccinated people become infected, the B cells can quickly unleash their antibodies against the viruses.
Unfortunately, a traditional flu vaccine can protect against only flu viruses with a matching hemagglutinin protein. If a virus evolves a different shape, the antibodies cannot latch on, and it escapes destruction.
Influenza’s relentless evolution forces scientists to reconfigure the vaccine every year. A few months before flu season, they have to guess which strains will be dominant. Vaccine producers then combine protein fragments from those strains to create a new vaccine.
Scientists have long wondered whether they could escape this evolutionary cycle with a vaccine that could work against any type of influenza. This so-called universal flu vaccine would have to attack a part of the virus that changes little from year to year.
Dr. Gilbert and her colleagues at Oxford are trying to build a T cell-based vaccine that could find such a target. When T cells learn to recognize proteins from one kind of virus, the scientists have found, they can attack many other kinds. It appears that the flu proteins that infected cells select to put on display evolve very little.
The scientists are testing a vaccine that prepares T cells to mount a strong attack against flu viruses. They engineered a virus that can infect cells but cannot replicate. As a result, infected cells put proteins on display, but people who receive the vaccine do not get sick.
In a clinical trial reported this summer, the scientists found that people who received the vaccine developed a strong response from their T cells. “We can bring them up to much higher levels with a single injection,” said Dr. Gilbert, the lead author of the study.
Once the scientists had vaccinated 11 subjects, they exposed them to the flu. Meanwhile, they also exposed 11 unvaccinated volunteers. Two vaccinated people became ill, while five unvaccinated ones did.
While the Oxford researchers focus on T cell vaccines, others are developing vaccines that can generate antibodies that are effective against many flu viruses — or perhaps all of them.
The first hint that such antibodies exist emerged in 1993. Japanese researchers infected mice with the flu virus H1N1. They extracted antibodies from the mice and injected them into other mice. The animals that received the antibodies turned out to be protected against a different kind of flu, H2N2. In hindsight, that discovery was hugely important. But at the time no one made much of it.
“By and large, people just said, ‘This is an oddity — so what?’ ” said Ian Wilson of the Scripps Research Institute.
Scientists did not appreciate its importance for more than 15 years, until Dr. Wilson and other researchers began isolating the antibodies that provided this kind of broad protection and showed how they worked.
The new antibodies turn out to attack different parts of the flu virus from the ones produced by today’s vaccines. Today’s vaccines cause B cells to make antibodies that clamp onto a broad region of the tip of the hemagglutinin protein. Recently, Dr. Wilson and his colleagues discovered a new antibody with a slender tendril. It can snake into a groove in the hemagglutinin tip.
Dr. Wilson and his colleagues found that this tendriled antibody can attach to a wide range of flu viruses. The results hint that the groove — which flu viruses use to attach to host cells — cannot work if its shape changes much.
The antibody is also impressively powerful, the scientists found. They infected mice with a lethal dose of the flu and then, after three days, injected the new antibody into them. The antibody stopped the virus so effectively that the mice recovered.
The hemagglutinin groove is not the only promising target for antibodies. Dr. Wilson and other scientists are discovering antibodies that attack the base of the protein. Influenza viruses can be broadly categorized into three types — A, B and C. Until now, scientists have found only antibodies that attack different versions of influenza A. Dr. Wilson and colleagues at Scripps and the Crucell Vaccine Institute in the Netherlands recently found a stem-attacking antibody that blocks influenzas A and B.
“The whole field is invigorated,” Dr. Wilson said. “It’s a great time.”
Building on these discoveries, Dr. Nabel and other scientists have recently developed vaccines that generate some of the new antibodies in humans. Now they are trying to figure out how to get the body to make a lot of the antibodies.
“Once you have an antibody that has all the properties you desire, how do you coax the immune system to make that?” Dr. Nabel said. “That’s the classic problem in immunology.”
The New York Times
Brisbane PhD candidate Connor O’Meara has been recognised with a research excellence award from biotechnology industry bodies and pharmaceutical companies for his innovative research into the common STI Chlamydia.
The research project undertaken with the Ken Beagley Chlamydia group at the Queensland University of Technology has looked at a vaccine for the disease, focusing on a vaccine ‘design’ that will prevent the associated complications – namely infertility.
“We’ve developed a vaccine that prevents infertility, specifically by suppressing the body’s harmful immune response, which is what causes the infertility.”
“What’s interesting about this vaccine is that the protection against infertility occurs independently of the control of infection.”
Which, Connor explains in simple terms means the vaccine doesn’t just protect against infection, but provides tolerance against the disease itself.
According to Mr O’Meara, Queensland has the highest rate of Chlamydia infection per capita in Australia, and untreated cases are costing the Australian Government between $90 and $160 million each year.
“Chlamydia is a major problem for Australia, and one of the main problems is that most infections are asymptomatic, and untreated infections can lead to infertility,” which he says is where the major health costs lie.
Recent statistics from the Australian Bureau of Statistics (ABS) highlight the transmission of the disease as a rapidly growing problem for Australia’s health system reporting “the rates in 2011 were triple what they were in 2001” in a recent Social Trends report on STI’s.
Mr O’Meara says that is why he became involved in the research for a vaccine.
“A vaccine has the greatest potential to stem the rise in infection and disease prevalence but vaccines developed against Chlamydia have largely failed to prevent infertility.”
Data released by the ABS suggest infection rates of the disease have risen to account for over 80 per cent of all sexually transmitted diseases in Australia, which Mr O’Meara finds concerning.
“It’s really on the increase, especially in developed countries like the US and Australia, and it is only getting worse,” he says.
According to the World Health Organisation a vaccine for the common STI “would have a significant impact on the spread of the disease,” however “the lack of a suitable animal model and the difficulties in genetic manipulation of the bacterium has hampered progress in the field”.
But at present there is no freely available vaccine for Chlamydia, the 80,000 new notifications of the disease each year in Australia are treated with antibiotics.
Mr O’Meara’s research is part of an ongoing research process for the university’s Institute of Health and Biomedical Innovation (IHBI) aimed at further developing the research from lab mice to an available needle-free vaccine.
“All researchers are essentially standing on the shoulders of giants, it’s a process, and so work that I do – people will come in after me and follow up that work so eventually what we will have at the end of it is an effective vaccine.”
“It would always be a great thing to be on the ground level for any kind of Chlamydia vaccine…[but] it is a very lengthy process and it can take up to decades unfortunately.”
After 3 years of hard days, long nights and hardly any weekend Mr O’Meara has submitted his research findings and can finally put the intense lifestyle of a PhD candidate to one side for a [little] while.
He will present his research when he recognised among his peers at an Australian biotechnology conference in early November.
Yale researchers have developed a new model for vaccination against genital herpes, a disease for which there has been no cure and no effective immunization.
Genital herpes, known formally as herpes simplex virus (HSV), is a mostly sexually transmitted infection (STI) that accounts for significant disease and morbidity. Until now, most efforts to develop a vaccine have focused on the immune system’s antibodies, or T cells, circulating through the body. When T cells encounter foreign invaders such as bacteria or viruses, they learn to recognize them and mount ever-stronger immune responses to fight them. But efforts to harness these circulating T cells have not been effective in organs such as the vagina, intestines, lung airways, and central nervous system, which restrict the entry of these “memory” T cells.
To investigate an alternative approach, the Yale team focused instead on peripheral tissue in the female genital tract, where viral exposure occurs. The challenge was to recruit virus-specific T cells into the vaginal mucosa without triggering a potentially harmful inflammatory response of the immune system.
Working with mice, they explored a two-part vaccine strategy they call “prime and pull.” The “priming” involved conventional vaccination to elicit a system-wide T cell response. The “pulling” involved recruitment of activated T cells directly into the vaginal tissue, via topical application, of chemokines — substances that help mobilize the immune cells.
They found that the recruited T cells were able to establish a long-term niche and offer protective immunity against genital herpes by reducing the spread of HSV into the sensory neurons.
The Yale team’s new vaccination model may offer a promising vaccination strategy against not just HSV, but potentially other STIs such as HIV-1. “This new vaccine approach can work with any vaccines that elicit strong T cell immunity, and will set the stage for protection against infectious diseases by setting up memory T-cells at the site of exposure,” said lead author Akiko Iwasaki, professor of immunobiology at Yale School of Medicine and a member of Yale Cancer Center’s molecular virology program.
“This technology can be potentially applied to other infectious agents that enter through a given portal, such as the genital tract, respiratory tract, the skin, or gut,” she added.
Advisers to the U.S. Centers for Disease Control and Prevention voted on Wednesday to recommend the use of GlaxoSmithKline’s newly approved vaccine for bacterial meningitis in babies at increased risk of the infection.
Children at increased risk include those with sickle cell disease and an immune system disorder known as complement component deficiency.
The CDC panel said the vaccine could also be used in babies 2 months through 18 months who live in communities battling an outbreak of meningococcal disease caused by serogroup C and Y.
The vaccine, known as MenHibrix, targets two common causes of bacterial meningitis, a serious infection of the thin lining surrounding the brain and spinal cord. It can cause severe brain damage, and it is fatal in 50 percent of cases if untreated.
The Advisory Committee for Immunization Practices, which advises the CDC, voted 13 to 1, with 1 abstention, to recommend the vaccine for use in infants at greater risk for meningococcal disease, with 4 doses starting at 2, 4, 6 months and 12 through 15 months.
The U.S. Food and Drug Administration approved the vaccine in June.
The vaccine is intended to prevent disease caused by the bacteria Neisseria meningitidis serogroups C and Y, two of the three most common causes of meningococcal disease in the United States.
It also protects against Haemophilus influenzae type b or Hib bacteria. Hib was the most common cause of bacterial meningitis in children under the age of 5 before vaccines for the strain became common.
About 4,100 cases of bacterial meningitis occurred in the United States each year from 2003 to 2007, the most recent data available, and 500 people died from the disease, according to the CDC. Infants are at highest risk.
Disease Amnesia hovers. It afflicts, for the most part, upper-income, upper-educated parents, vigilant over their children’s safety. You can spot the parents buying fiddlehead ferns at Whole Foods, coaching soccer games, volunteering at PTA meetings.
Their mission: protect their children from bad food, bad water, bad air. In short, protect them from harm.
They have latched onto a modern-day harm: vaccinations.
A swatch of parents has always rejected vaccinations, citing religious, or medical, reasons. But in the past decade, that swatch has swelled to include parents with “philosophical” objections. They distrust government mandates to inject their healthy children with vaccines. They don’t believe that those injections will keep their children healthy. Instead, they espy a plot: pharmaceutical companies allied with physicians allied with government. Forget bacteria. Forget clinical trials. These parents see, at best, a needless expense, at worst, an evil cabal.
In the spirit of accommodation, states have expanded the criteria for parents to opt out of children’s vaccinations. Some states require a note from a physician and/or clergyman; some require a signed statement of objection from the parents; in some states, parents need only check a box. Two states – Mississippi and West Virginia – allow only medical exemptions, attested by a physician. The National Vaccine Information Center, “grassroots activists working to protect and expand vaccine exemptions,” has compiled a state-by-state list: (http://www.nvic.org/Vaccine-Laws/state-vaccine-requirements.aspx ).
Not surprisingly, in states with “easier” opt-out procedures, more parents have opted out. In 2011, 3.3% of parents opted out for non-medical reasons in states with “easy” exemption policies; 1.3% in states with more stringent ones. Yet in all states, the number of parents sparing their children shots, but exposing them to disease, has grown. (“Vaccination Policies and Rates of Exemption from Immunization, 2005–2011,” Correspondence, New England Journal of Medicine, Sept. 20.) In Washington State, in 2008, 7.6% of kindergarten parents opted out. The new norm seems to be a parental “no” to vaccines.
The result: again not surprisingly, a resurgence of once-rare childhood diseases.
Whooping cough is the first to resurge. In 1950 the country had 120,718 cases; by 1976, the number had plunged to 1,010. In 2010, we had 27,550 cases. The federal Centers for Disease Control and Prevention expects 2012 to top that. In Washington state, physicians reported 3,014 cases as of July 14; the same time in 2011, physicians reported 219 cases. The reason for the initial plunge: vaccinated children. The reason for the upswing: unvaccinated children.
Indeed, statistics show a near- eradication of some diseases, like tetanus and diphtheria. Polio was the great killer: at its peak, in 1952, the country had 57,628 cases. Both measles and German measles were common childhood diseases – sometimes with severe disabling ramifications, sometimes fatal – 50 years ago. But vaccination campaigns worked, and cases plummeted, until recently. Today measles has returned: in 2011 there were 17 outbreaks, with 222 cases. The source: unvaccinated children, and adults who contracted measles overseas.
Disease amnesia is baffling. These parent-sufferers distrust government’s alliance with Big Pharm. But they also suffer from real amnesia: victims have forgotten these diseases, which remain both dormant and contagious. One unvaccinated child in a herd of vaccinated people is safe; a cluster of unvaccinated children invites the disease back. The whooping cough that is benign for one child may be fatal for a newborn. The measles that gives one person a rash may leave another blind. But parents have forgotten that sad history, the reason older generations embraced vaccination campaigns.
Washington State recently made it harder to opt out: the state now requires parents to get a physician’s signature. (Sabrina Tavernise, “Washington State Makes It Harder to Opt Out of Immunizations,” New York Times, Sept. 19). Vaccinations have increased. Presumably once a disease breaks out, other states will follow Washington’s lead.
In the meantime, perhaps all parents should watch the History Channel. They should venture back to the 1950s, before widespread vaccination campaigns, when parents were powerless to protect their children from killer diseases.
Human respiratory syncytial virus (HRSV) is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.
Korean Journal of Pediatrics