Immune system may prevents MRSA infection

Researchers at Johns Hopkins, the University of California, Davis, and the National Institute of Allergy and Infectious Diseases have discovered how the immune system might protect a person from recurrent bacterial skin infections caused by Staphylococcus aureus (staph). "There's a huge, unmet clinical need for new approaches against staph skin infections because of declining antibiotic development and rising drug resistance," says Lloyd Miller, M.D., Ph.D., associate professor of dermatology at the Johns Hopkins University School of Medicine.

Staph is a common bacterium and the most common cause of skin infections in people. Additionally, multidrug resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), are causing severe skin infections in healthy people outside of hospitals. And once you've had an infection, the recurrence rate is 50 percent within six months. Staph can also spread from the skin and cause invasive and life-threatening infections such as sepsis, osteomyelitis and pneumonia.

Using mice with defective immune systems, research team found that after an initial exposure of the skin to staph, they were surprisingly protected against a second skin exposure with the same bacteria. After testing for antibodies and other usual suspects of the immune system against this infection, it was not clear what immune response was protecting the mice. The researchers then tested a drug FDA-approved for treatment of multiple sclerosis, which acts by preventing certain immune cells from leaving lymph nodes for sites of inflammation.

That genetic sequencing data revealed that specific cells substantially multiplied after the initial infection, then moved to the infection site and provided protection against the second infection. These so-called gamma delta T cells account for less than 1 percent of all the cells in the lymph node prior to infection. After infection, they accounted for more than 20 percent.

Working with collaborators from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, the researchers tested blood from healthy individuals and people with a rare immune disorder that makes them highly susceptible to staph skin infections. Half of people with the disorder die by age 10, but if they survive to adulthood they somehow overcome their susceptibility to staph infections.

In blood samples from these patients, the researchers found an increase in the percentage of gamma delta T cells, similar to what they observed in mice, which remained stable over years. The findings and especially gamma delta T cells may be targeted for developing new therapies or a vaccine against staph skin infections.

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HIV vaccine production

Research on HIV over the past decade has led to many promising ideas for vaccines to prevent infection by the AIDS virus, but very few candidate vaccines have been tested in clinical trials. One reason for this is the technical difficulty of manufacturing vaccines based on the envelope proteins of the virus, according to Phil Berman, who led development of a major component of the only vaccine to have shown any efficacy against HIV in a clinical trial.

Berman, the Baskin Professor of Biomolecular Engineering at UC Santa Cruz, has now developed new methods for the production of HIV vaccines. His approach solves major technical problems which have bedeviled the field. Berman described the new methods, and the candidate vaccines his lab has produced.

Researcher was able to use robotics to shorten the time required to produce stable cell lines, needed to make the proteins for a vaccine, while at the same time greatly increasing how much of the protein the cell lines can produce. The improved yield makes it possible to reduce the size of the bioreactor needed to make vaccine for large clinical trials—from 200- to 10,000-liter vessels to 50- or 100-liter vessels—resulting in tremendous savings in the equipment required and cost of materials.

They were  able to create cell lines that make HIV envelope proteins with the right kind of carbohydrate components (called glycans) needed for an effective immune response. The carbohydrates attached to the protein are really important, something no one realized until recently. The conventional way of making these envelope protein vaccines incorporated the wrong kind of carbohydrates.

Cell lines derived from Chinese hamster ovary (CHO) cells are the industry standard used to produce complex recombinant proteins for therapeutic use. These cells are also useful for the production of HIV vaccines. The gene for the desired protein is transferred into CHO cells in a process called transfection, and tens of thousands of transfected cells are screened to find the few rare cells that produce large amounts of the protein. The best cell lines are grown in large batches, in a process similar to yeast fermentation for making beer, and the proteins are then isolated and purified.

Berman's lab developed a new robotic method to isolate high-producing cell lines making HIV envelope proteins. This shortened the time required to produce stable cell lines from 18 to 24 months to just 2 or 3 months, while increasing yields by a factor of 100 to 200. Those improvements are in comparison with Berman's previous experience creating the AIDSVAX vaccine, first at Genentech and then at VaxGen.

Fluorescent antibodies were used to label the HIV gp120 protein and identify high-producing cell lines. Credit: Phil Berman, UCSC. AIDSVAX was one component of an experimental vaccine regimen used in a large-scale clinical trial known as RV144, which showed 31 percent efficacy in preventing new HIV infections. The RV144 results showed that protection was correlated with antibodies to a certain segment of an HIV envelope protein called gp120.

 The original AIDSVAX vaccine had the completely wrong type of carbohydrate, and that we might improve the level of protection if we could find a way to make it with the proper type of carbohydrate. They set out to create a cell line that can produce the unusual glycans found on HIV envelope proteins rather than the complex glycans CHO cells normally produce. This was made possible by the powerful new gene editing technology known as CRISPR/Cas9.

 They used CRISPR to create a new cell line they called MGAT CHO, which produces proteins lacking complex glycans containing sialic acid and enriched for the simple "high mannose" type found on HIV envelope proteins. An unexpected benefit of this new cell line was that it enabled a simpler, less expensive process for recovering and purifying the proteins.

Carbohydrates may not be immunogenic, but HIV turns out that the most important antibodies are directed to carbohydrate. It leads to an improved version of the vaccine used in the RV144 trial. Berman's lab currently has two cell lines he said are ready to start producing vaccines on a large scale. He is now looking for partners and funding to bring them into clinical trials. Researchers have continued to use the AIDSVAX vaccine in clinical studies because it has been so hard to make new HIV vaccines.
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Roles of bacteria in colon cancer

Patients with an inherited form of colon cancer harbor two bacterial species that lead to development of the disease, and the same species have been found in people who develop a sporadic form of colon cancer, a study led by a Johns Hopkins Bloomberg~Kimmel Institute for Cancer Immunotherapy research team finds.

A second study by the same researchers shows a possible mechanism behind how one of these species spurs a specific type of immune response, promoting-instead of inhibiting the formation of malignant tumors. Together, these findings could lead to new ways to more effectively screen for and ultimately prevent colon cancer.

The Science findings describe a process in which these bacteria invade the protective mucus layer of the colon and collude to create a microenvironment-complete with nutrients and everything the bacteria need to survive that induces chronic inflammation and subsequent DNA damage that supports tumor formation.

These findings suggest a change in the standard of care for people who carry both types of bacteria. "More frequent colon cancer screening than the currently recommended once every 10 years should be considered," says Drew Pardoll, M.D., Ph.D., director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy. Ultimately, once better understood, administering drugs or vaccines to prevent colonization of the bacteria in the colon, and potentially even probiotics to chase the bugs from the colon, are preventive measures that could be explored to interrupt the cancer-promoting process.

These new findings shows that particular strains of bacteria can invade the colon mucus in some patients who get colon cancer but who have no inherited predisposition for the disease. Unlike most bacteria, which do not make it past the colon's protective mucus layer, these communities of bacteria that invade the mucus form a sticky biofilm right next to the colon epithelial cells that line the colon, where colon cancer usually originates.

About 5 percent of colon cancers are caused by a hereditary syndrome called familial adenomatous polyposis (FAP), in which an inherited mutation launches a series of genetic changes that develop over time and eventually prompt the epithelial cells to turn malignant. However, it was unclear whether ETBF or other bacteria played a role in the progression to colon cancer in FAP patients.

To investigate the relationship between the bacteria-caused biofilms and cancer formation, researchers examined colon tissue removed from six FAP patients. Tests showed patchy sections of biofilms distributed along the colon's length in about 70 percent of the patients. The researchers used gene probes to identify the particular bacterial species and found that the biofilms consisted mainly of two types, Bacteroides fragilis and Escherichia coli, a surprising finding since the colon contains at least 500 different types of bacteria.

Tests on 25 additional colon samples from FAP patients showed that the B. fragilis strain was a subtype, called ETBF, which makes a toxin that triggers certain oncogenic, or cancer-promoting, pathways in colon epithelial cells and causes colon inflammation. The E. coli strain produced a substance called colibactin (synthesized by a set of genes in the bacterial genome called the PKS island), which causes DNA mutations.

FAP is a devastating disease that ultimately results in surgical removal of the colon, a Currently, using colonoscopy to monitor for the formation of precancerous tumors, called polyps, is the standard of care. Using a mouse model of colon cancer, the researchers found that animals whose colons were colonized with just one of these species developed few or no tumors. However, when their colons were colonized with both species simultaneously, they developed many tumors, suggesting a synergy between the two types of bacteria.

An earlier study suggested a unique type of immune response producing an inflammatory protein called IL-17-was key to ETBF-induced tumor formation. In order to prove the importance of IL-17 in the cancer-promoting effects of the bacterial combination, they used a mouse model in which the IL-17 gene was genetically deleted so it could not make IL-17, and colonized the mice with both ETBF and PKS+E. coli. Unlike animals that readily made IL-17, the genetically altered mice didn't form colon tumors, confirming the importance of this protein in bacterial-driven colon cancer.

However, in addition to IL-17, the studies showed that ETBF digested the mucus layer, enabling the PKS+ E. coli to adhere in larger numbers to the colon mucosa where together the bacteria induced increased DNA damage, a step preceding the gene mutations that underlie colon tumor formation. The complementary findings in Cell Host & Microbe demonstrate how ETBF's toxin prompts colon cancer to develop. Using a different mouse model of colon cancer, the researchers colonized the animals' colons with ETBF and then performed a series of tests to monitor the resulting cellular and molecular changes.

Their results revealed that ETBF's toxin spurs a cascade of events that promote colon inflammation that feeds back to act on the colon epithelial cells. First, the toxin triggers colon immune cells to produce IL-17. This inflammatory molecule then acts directly on the colon epithelial cells to trigger activation of a protein complex involved in promoting further inflammation, known as NFkappaB. NFkappaB in turn induces the colon epithelial cells to produce several signaling molecules that recruit more immune cells, called myeloid cells, to the colon.

These immune cells are involved in the inflammatory response and are known to support tumor growth. This process culminates in tumors forming in the colon. Additional experiments showed that a protein known as STAT3, which was previously shown to play a role in regulating cancer and inflammatory genes, is also necessary for tumor formation.
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Fish oil protects vision cells

A component of fish oil not only protects cells critical to vision from potentially lethal initial insults, but also from those that occur in the future. The omega-3 fatty acid, DHA, and its derivatives "precondition" photoreceptor and retinal pigment epithelial (RPE) cells to survive.

DHA and docosanoids (molecules made in the brain at the onset of injury or disease) are responsible for activating sustained cellular mechanisms that elicit long-term preconditioning protection. A preconditioning PC stimulus is a sub-lethal or pharmacologic stressor that activates a counter-regulatory protective response to a future lethal stimulus. Preconditioning takes place when the blood supply to an organ is interrupted for a short time and then reestablished.

The protective response from that first injury would carry over to a subsequent blood supply shortage, much like the immunity a vaccine confers against future exposures to disease. This happens in the heart, brain and retina, as well as other organs. To harness the therapeutic potential of preconditioning, it is very important to identify the molecules directly involved.

Fish oil contains two types of polyunsaturated fatty acids (PUFAs) -- omega-3 (docosahexaenoic acid or DHA) and omega-6 (arachidonic acid or AA). They have distinctly different actions. Omega-3 PUFAs and their enzymatic metabolic derivatives, docosanoids, display potent anti-inflammatory and pro-resolving properties in contrast to the pro-inflammatory actions of omega-6 PUFA derivatives. The researchers found that although they are released concomitantly, DHA can alter the action of AA. When they supplemented DHA prior to the oxidative stress insult, the synthesis of protective DHA derivatives increased while AA synthesis decreased over time.

DHA and the induction of docosanoid synthesis is necessary for preconditioning protection, and thus daily survival, of photoreceptor and RPE cells. Omega-3 impairments are associated with neuroinflammation, which contributes to photoreceptor cell dysfunction and death, enhancing the synthesis of docosanoids may provide an opportunity for halting or ameliorating debilitating retinal degenerative diseases, such as the dry form of age-related macular degeneration.
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Dengue immunity can protect against Zika

Manifestations of Zika virus (ZIKV) infection differ drastically. Sometimes they are catastrophic, most notably when they cause microcephaly in some babies born to infected mothers. At other times, they are mild and fleeting, suggesting that unknown factors temper Zika infections' severity.

Recently, dengue virus emerged as a prime suspect because it shares many genetic and structural characteristics with ZIKV and is endemic in most of the regions affected by Zika's global spread.
Mice rendered immune to dengue show "cross-protection" from subsequent Zika infection and then identifies specific types of immune T-cells capable of defending against both viruses.

These revelations have profound implications for efforts to build a potent anti-Zika vaccine. In some parts of the world Zika is almost like a secondary infection. It has spread into Brazil/Latin America and is moving into places in Asia where people previously had dengue. Vaccines targeting either virus could be engineered to induce both T cell and antibody responses effective to protect people in these areas.

When one encounters a pathogen in real life, two arms of the immune system spring into action to neutralize it. In the so-called humoral response, B-cells begin to secrete specific antibody proteins, which latch onto and neutralize pathogens in tissue or blood. Simultaneously, a cell-mediated immunity system also becomes active, deploying cytotoxic T-cells to directly recognize and kill pathogen-infected cells.

The ideal vaccine might mimic both antibody and T cell responses to block an infectious disease. But in truth, most (26 of 28 vaccines currently licensed for human use) stimulate primarily a B-cell or antibody response, which in many cases is sufficient. Reseache team created the first "sequential" mouse model mimicking dengue-then-Zika infection. To do that, they infected mice genetically vulnerable to this family of viruses with dengue virus.

Those mice became sick, recovered from infection, and hence acquired immunity to dengue, presumably because viral infection had mobilized their immune B-cells, T-cells or both. The group then inoculated the same mice with ZIKV and waited to see if mice showed ZIKV symptoms. But overall, mice that had previously acquired dengue immunity showed protection against Zika, as evidenced by a reduced burden of ZIKV in blood and tissues, such as brain, liver or testis, compared to control mice not "pre-inoculated" against dengue.

These experiments suggest that the reason that some people infected with Zika do not come down with disease is due to prior exposure to dengue. This may explain why Zika is not passed to the unborn child of every pregnant woman in dengue-endemic countries exposed to virus. In a different experiment, the scientists isolated cytotoxic T cells from the blood of dengue-immune mice and infused them into normal mice, a procedure known as adoptive T-cell transfer.

 When infused mice were then infected with ZIKV, they also showed disease resistance, supporting the idea that the T-cell arm of the immune system can do the heavy lifting against ZIKV infection. A successful vaccine would need to include components to induce not only a B-cell response but also a T-cell response.
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HPV vaccine prevents childhood respiratory disease

The vaccine that protects against cancer-causing types of human papillomavirus HPV also prevents an uncommon but incurable childhood respiratory disease, the chronic and difficult-to-treat condition, recurrent respiratory papillomatosis.

The condition is thought to occur in children when HPV type 6 or 11 is spread from mother to child around the time of birth. In some children, the virus can cause wart-like, non-cancerous growths called papillomas to develop in the respiratory tract, eventually making it difficult to breathe.

 The condition can be life-threatening, and repeated surgeries are usually required to keep the airway clear. Medical costs related to the disease in children. The Centers for Disease Control and Prevention CDC currently recommends two doses of the vaccine for teens younger than 15 and three doses for those who start the vaccine series at ages 15 through 26.

Recurrent respiratory papillomatosis is an uncommon but difficult-to-treat respiratory disease caused by certain types of human papillomavirus HPV. In children, the chronic disease is thought to occur when HPV is spread from mother to child around the time of birth, later causing recurring growths in the respiratory tract that usually require repeated surgeries to remove.
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Risk factors for Marburg infections

People at risk of Marburg infection are those who come in contact with African monkeys and bats, researchers on these viruses are also at higher risk of becoming infected, African miners due to their exposure to bats. Veterinarians may also be at higher risk if they are exposed to African monkeys. Also, people who care for Marburg virus-infected patients and health workers who remove those bodies of deceased Marburg virus-infected patients are at high risk of contracting the disease.

Patients are given supportive hospital care by maintaining their fluid and electrolyte balance and other considerations, such as replacing lost blood and maintaining a good oxygen supply. This supportive care is most effectively done in an intensive-care hospital unit. Most individuals with Marburg virus infections are treated in hospitals in the intensive-care units. Specialists who treat the patient are critical-care specialists, hematologists, infectious-disease specialists, hospitalists, and lung specialists.

There is no antiviral drug or vaccine approved for use in humans against Marburg viruses. Preventive measures are based on barrier techniques (isolation techniques) that isolate the infected patient from other humans. Those health-care professionals who treat Marburg virus-infected patients must use barrier protections such as gowns, gloves, masks, and shoe coverings.

The prognosis for Marburg infection ranges from fair to poor. The fatality rate varies from about 23%-90%. Individuals cared for in an intensive-care unit have a better chance of survival. Complications that can occur with Marburg infection include the following: inflammation of the retinas of the eyes, inflammation of the testes,
liver inflammation, inflammation within the pigmented layer of the eye, inflammation of a segment of the spinal cord and brain inflammation.

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Effectiveness of cervical cancer vaccine

A vaccine that can eradicate the majority of cervical cancer cases shows long-term effectiveness, researchers examined different women in different countries after taking the vaccine the results showed that vaccination with Gardasil 9 can reduce 90 percent of cervical cancers.

The vaccine is unique in its ability to prevent certain cancers. HPV infections cause global disease and deaths. Routine screening by Pap smears or tests for HPV infection has reduced death rates. Vaccination against the sexually transmitted human papillomavirus HPV prevents some cancers.

The vaccine immunizes against nine genotypes of HPV known to cause cervical cancer, as well as vulvar, vaginal and anal cancers and genital warts caused by HPV.

Gardasil vaccine targets the two HPV genotypes that caused about 70 percent of cervical cancer and two other genotypes that cause genital warts. Gardasil 9 targets those four genotypes and five others. Both vaccines are prophylactic, meant to be given before females or males become exposed to HPV infection through intimate contact.

Women were followed for efficacy at preventing disease for up to six years after the first vaccine shots, and they were followed for production of infection-halting antibodies against the nine genotypes of HPV for more than five years.

They were followed by gynecological examination for evidence of infections or disease, and their blood sera were tested for antibody levels against HPV.
Gardasil 9 showed 97.4 percent efficacy to prevent infections and disease caused by the five additional HPV genotypes not included in the four-valent Gardasil vaccine. Gardasil 9 vaccination produced similar antibody protection against the four HPV genotypes in Gardasil.
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Meningococcal B vaccine may prevents gonorrhoea

Vaccine used against a bacteria that causes brain inflammation can prevents gonorrhoea. Presently, using a condom or abstaining from sex are ways of preventing gonorrhoea.

Gonorrhoea can cause painful pelvic inflammation in women, and infertility in men and women. It can also spread into the bloodstream to cause life-threatening infections in other parts of the body. Infected pregnant woman can pass it to her fetus and cause blindness.

The disease spreads easily because many carriers are unaware of the disease, until they experience the symptoms. Gonorrhoea is becoming untreatable because of antibiotic resistance, there is an increased imperative to examine different vaccine for the treatment.

Researchers examined gonorrhoea cases among people who have used meningococcal B vaccine for Meningococcal bacteria, they noticed a decline in gonorrhoea after the use of meningococcal B vaccine.
This shows that meningitis vaccine can prevents gonorrhoea.
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HPV vaccine can reduce cervical cancer

Cervical cancer affects more than half a million women and causes more than a quarter of a million deaths globally.
Cervical cancers result from a human papillomavirus, or HPV infection.

HPV infections can cause cancers in other parts of the body, the latest HPV vaccine could prevent infections and many cancers.

The HPV vaccine could prevent up to 90 percent of HPV-related cancers, the vaccine can prevent HPV infection if the vaccine is given before exposure to any of the HPV types that the vaccine protects against.

 Different formulas of the HPV vaccine protect against different types of HPV. Only two types, HPV16 and HPV18, cause 70 percent or more of all invasive cervical cancers and all HPV vaccine formulas protect against these two.

 The nonavalent formula of the HPV vaccine is the most protective: it protects against HPV16, HPV18 and five other cancer-causing HPV types.

Experts estimate that the nonavalent HPV vaccine could reduce HPV-related cancers worldwide by 90 percent or more if the entire global population received it.
     


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Zika RNA found in Aedes albopictus

Chelsea Smartt, an entomology associate professor and her research team collected 20 female and 19 male Aede albopictus mosquitoes eggs and raised them to adults and tested the adults for the Zika virus RNA

They discovered that five of them are positive for Zika RNA, this shows that Zika virus is present in mosquito that is not associated with the virus.

Mosquitoes like Aedes albopictus can be infected with zika virus in an area that has high density of zika virus.

Avoid mosquito bites and sleep under insecticide mosquito net at night. Presently, their is no vaccine for zika virus.

Vaccine protects mice from Zika virus

New Zika vaccine was made from live virus that has been inactivate and it shows effectiveness in mice.

Producing a better vaccine will require a balance between efficacy and safety of the user, vaccine produced from attenuated live viruses normally offers fast immunity but not safe.

Inactivated and subunit viruses always provide safety but may required several initial doses, safe live-atteuation  vaccine will be used for production of Zika vaccine for human in developing countries.

Zika vaccine showed safety profile in mice, this vaccine will prevent transmission of the virus and microcephaly and prevent birth defects and diseases caused by Zika.

The vaccine will be recommended for women of child bearing age, their sexual partner and children less than 10 years.

HPV Virus can cause cancer

Humans papillomavirus HPV that causes cancer affects 25 percent of men and 20 percent of women according to new government statistics.

People less than 25 years can be protected by vaccine from strains of HPV that causes a range of cancers.

Some HPV can cause genital warts, this have low risk of causing cancer. Other types causing cancer in different areas of the body like cervix, vagina, penis, anus and oropharynx are considered high risk.

According to experts, 70 percent of all head and neck cancer are caused by HPV and it affected more men than women.