Monday, 21 May 2018

Gold Nanoparticles in HIV Drug Delivery System

In a study, researchers believe that gold nanoparticles may breathe new life into once-promising drug candidates, in particular a compound designed to stop the spread of HIV (human immunodeficiency virus) that was shelved because of side effects. The compound TAK-779 was first proposed by researchers in 1996 and proved effective at blocking the virus from infiltrating body's immune system. But it was scuttled by 2005, because recipients suffered severe irritation at injection sites and oral doses were ineffective.

Researchers have known for years that ammonium salt molecules in the compound triggered the bad reaction. But they could not find a benign replacement able to perform its function of binding the drug to T cells, white blood cells that fight infection including HIV.

Given TAK-779's success, however, Christian Melander, an assistant professor of chemistry at North Carolina State University in Raleigh, says scientists continued to search for a substitute, which they may finally have found.

Melander and colleagues David Margolis, a professor of infectious disease at the University of North Carolina at Chapel Hill, and Daniel Feldheim, an associate professor of analytical and materials chemistry at the University of Colorado at Boulder, reported online in the Journal of the American Chemical Society that gold nanoparticles may be the answer.

Scientists have already established that microscopic particles including gold and silver can help ferry chemical compounds from one place to another in lab tests. Massachusetts Institute of Technology (M.I.T.) engineers since 2004 have been studying the potential of gold nanoparticles (coated with alternating bands of two different kinds of molecules) in particular to penetrate the protective membranes around cells without damaging them.

But, whereas the M.I.T. scientists are using nanoparticles simply as an agent to assist drug delivery, Melander and his team want nanoparticles to also be an integral part of the drug itself. Melander says the key was to determine whether gold nanoparticles would, like the ammonium salt, latch onto receptors (protein molecules embedded in a cell's membrane) on the outside of T cells to shield them from HIV.
Researchers found during lab tests that attaching 12 molecules of TAK-779 modified to exclude ammonium salt molecules to one gold nanoparticle restored the drug's ability to prevent HIV infection.

The size of the gold particles two nanometers (two billionths of a meter) in diameter is comparable to that of the HIV proteins they are trying to block. This should make them well suited to stop viral proteins from coming in contact with key receptors, says Joseph Wedekind, an associate professor of biochemistry and biophysics in the University of Rochester School of Medicine and Dentistry.

The problem is that HIV targets different receptors on T-cells and researchers only tested their compound on one of them. Another potential hitch is HIV's ability to mutate, and thereby become resistant to treatments over time, Melander says.

He notes that the next step will be to do a long-term study on whether HIV could change, eventually rendering the new compound impotent. Melander and his colleagues are also probing whether gold nanoparticles can be used to deliver an anti-HIV medicine directly to the human brain, where HIV is known to hide, replicate and mutate.

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Friday, 18 May 2018

Nanomedicine to Eradicate HIV

In a significant breakthrough that could hasten an eventual HIV cure, a research team at the University of Nebraska Medical Center has changed the chemical structure of an existing antiviral drug to facilitate it in reaching cells and tissues where HIV resides.

Using a physiochemical scheme that alters the properties of the drug dolutegravir, UNMC scientists took the modified drug and placed it into nanocrystals. The produced drug crystals easily distributed throughout the body to tissue reservoirs of HIV infection.

The advanced drug scheme extended the life of the drug and its entry into "hidden body compartments" from the muscle site of injection while increasing its action in reducing viral growth. The tissues included the lymph nodes, the bone marrow, the intestine and the spleen.

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The modified drug crystals were not toxic, did not break apart with temperature changes and were stable for months of time. All organs and bodily functions remained intact after treatment.

Coated with parts of fat, the crystals efficiently maneuvered through cell protective membranes and were stored inside cells for weeks said Howard Gendelman, M.D., professor and chair, who with Benson Edagwa, Ph.D., assistant professor, co-led the study in UNMC's Department of Pharmacology and Experimental Neuroscience (PEN).

Once stored inside cells called macrophages, the drug was slowly released from the crystal in an altered inactive form called a "prodrug." The cell then breaks the prodrug into an active drug, and the active drug is then released into the circulation from the cell and tissue stores.

"The strength of this system is that it not only can be effective in improving HIV care and prevention," said, Dr. Edagwa, who designed the drug chemical modifications, "but can be applied to many classes of drugs beyond HIV, such as drugs used to treat cancer, other infectious diseases and degenerative diseases that affect the brain."

Importantly, Dr. Gendelman said, "the new products can optimize HIV restrictive growth so that strategies that may eradicate viral infection would be successful."

UNMC has embraced the project, Dr. Gendelman said, with plans to soon complete a nanomedicine production plant that will enable the drugs and others like it to be produced on campus beginning this fall. Located on the 11th floor of The Lied Transplant Center, the plant will be a good manufacturing facility with an operating function similar to many pharmaceutical companies.

Patents have been filed and supported both by UNeMed, UNMC's technology transfer partner, and ViiV Healthcare, a subsidiary of GSK (GlaxoSmithKline). The research was funded by ViiV Healthcare and by research grants from four institutes of the National Institutes of Health -- Drug Abuse, Mental Health, Neurological Disorders and Stroke, and Aging.


Wednesday, 16 May 2018

Hopes for Gonorrhea Vaccine

Beginning in 2004 and lasting through 2006, a mass vaccination campaign inoculated most of the New Zealand population: about 90%, including 81% of those under age 20. New Zealand scientists then published their results for the impact of the vaccine on the outbreak.

"The emergence of completely drug-resistant gonorrhoea is a major concern," Dr. Helen Petousis-Harris, lead author of the new study and a senior lecturer at the University of Auckland, wrote in an email.

Evidence from a mass vaccination campaign for an outbreak of bacterial meningitis in New Zealand had unexpected results: reduced rates of the sexually transmitted disease gonorrhea, a study published Monday in the journal The Lancet finds. It is the first time a vaccine has shown any protection against gonorrhea.
In recent years, gonorrhea has shown increasing antibiotic resistance, with some patients unable to be treated with any available drug. Because of this, the World Health Organization includes gonorrhea in its list of bacteria that pose the greatest threat to human health.

She explained that "even moderate protection" against the sexually transmitted disease could have significant impact because the bacteria that cause it "are very tricky." They develop resistance to drugs by transferring genes in atypical ways and recombining with related bacterial species.

Meningococcal disease, the bacterial form of meningitis, is a serious infection of the meninges, the membrane covering the brain. It's transmitted from person to person, usually in close contact, such as kissing, sneezing or coughing, or living in close quarters with an infected person.

A vaccine targeting the specific strain of bacteria causing meningococcal disease in the New Zealand outbreak was eventually "developed in a collaboration between Chiron Vaccines, the National Institute of Public Health of Norway (NIPH) and the New Zealand government," according to Mary Anne Rhyne, director of corporate communications at GlaxoSmithKline, the pharmaceutical company that inherited the vaccine from Chiron through a series of corporate acquisitions.

The vaccine targeted the vesicle, or sac, on the outer membrane of the bacteria.

images"I wondered, in looking at their results from the outbreak, if there was any possibility that this vaccine might have had any other effects," said Black, who focused on the country's gonorrhea statistics in particular.

Neisseria gonorrhoeae bacteria (which cause gonorrhea) and Neisseria meningitidis bacteria (which cause meningococcal disease) are "two related organisms. They're cousins, if you will," he said, explaining that the genetic makeup of the two is "85 to 90% similar."

Petousis-Harris and her co-researchers, who had access to a database recording events during the meningococcal B outbreak, set to work testing his hypothesis.

"We compared the vaccination rates in two groups of people," Petousis-Harris explained. One group had gonorrhea, and the other group had chlamydia, both of which are spread through sexual contact.
If the vaccine had an effect against gonorrhea because it is an organism related to meningococcal disease, the researchers hypothesized, then no effect should be seen against chlamydia, an unrelated organism.

"This is exactly what we saw," Petousis-Harris wrote in an email. "We found that people with gonorrhoea were less likely to be vaccinated than people with chlamydia," indicating that the vaccine protected against gonorrhea but not chlamydia.

The researchers also discovered that vaccinated people were significantly less likely to become infected with gonorrhea than people who had not received the vaccine: 41% vs. 51%.

Taking other factors into account, including ethnicity and gender, the researchers concluded that having received the meningococcal vaccine reduced the incidence of gonorrhea by about 31%.

"Given the emergence of drug resistance, a vaccine may be our only avenue," Petousis-Harris said.


Tuesday, 15 May 2018

HPV Vaccination in Prevention of Cervical Cancer: Review


The human papillomavirus or HPV spreads through intimate contact during sex with someone who is infected. In some women, an HPV infection will persist and lead to cervical cancer. HPV vaccines protect against cervical cancer in young women, especially when the women are vaccinated between the ages of 15 and 26, a new Cochrane Report finds.

The report's authors, who examined evidence from 26 previously published studies of more than 70,000 women, also found no serious side effect risks associated with the vaccines.

Most people who have sexual contact will be exposed to HPV at some time. Even if exposed, most women will clear the viral infection naturally. However, a persistent infection could lead to abnormal cervical cells, called cervical "pre-cancer" since these cells can slowly progress to cancer if not treated.

"Cervical cancer is the fourth most frequent cancer in women in the world," said lead author Dr. Marc Arbyn of the Unit of Cancer Epidemiology at the Belgian Cancer Centre in Brussels. More than half a million cases are diagnosed each year, and about half of these women will die of the disease, he said.

Though there are many types of HPV, only some strains raise a woman's risk for developing cervical cancer; HPV16 and HPV18 account for about 70% of all cases of cervical cancer worldwide.

For the new review, Arbyn and a team of researchers evaluated study evidence for two commercially available HPV vaccines: Cervarix, which targets HPV16 and HPV18 only, and Gardasil, which takes aim against those strains plus two HPV types that cause genital warts.

The World Health Organization recommends HPV vaccination for both girls and boys between the ages of 9 and 14. The United States, the UK, Australia and nations in the European Union all have similar if slightly different guidelines, though only some include boys. Since not all the studies in the review included boys, the researchers did not examine evidence of HPV vaccine effectiveness pertaining to men.

In women between the ages of 15 and 25 who tested negative for HPV before receiving the vaccine, the risk of precancer associated with HPV16 or HPV 18 was 164 for every 10,000 unvaccinated women, compared with just two per 10,000 vaccinated women. The vaccines also reduced the risk of any cervical precancer (whether caused by the two HPV types or not) from 287 to 106 for every 10,000 women.

In older women -- those vaccinated between the ages 25 and 45 -- the effects of HPV vaccine were smaller, the authors estimate. Unvaccinated versus vaccinated, the risk of precancer associated with HPV16 and HPV18 dwindled from 145 to 107 for every 10,000 women. This is probably due to the women having been previously exposed to HPV, the authors said, adding that the vaccine did not provide protection against any cervical precancer.

Despite claims and reports that the vaccine causes neurological issues -- including seizures -- Arbyn and his colleagues found local reactions, such as a swollen arm, when receiving either of these two vaccines but "no increased incidence of serious adverse effects." However, the reviewers added that "evidence on rare potential harms ... are difficult to capture" in the types of studies reviewed.

Dr. Jo Morrison, a consultant in gynaecological oncology at Musgrove Park Hospital in Somerset in the UK, said the claims that the vaccine damages young girls "are not substantiated by the evidence." Morrison, who was not involved in the study, added, "going down this road risks causing harm by reducing vaccination rates."

Overall, Morrison believes "the review reassures people that HPV vaccination is effective. They should be encouraged to vaccinate their daughters, as per the government recommendation."
Helen Bedford, a professor at University College London's Institute of Child Health, noted that "HPV vaccine was introduced 10 years ago for 13- to 14-year-old girls to prevent infection with HPV, which can lead to cancer of the cervix."

"This, together with early evidence of reduction in cervical cancer in Finland, confirms the ground breaking value of this cancer-preventing vaccine," said Bedford, who was not involved in the study. "It also provides reassuring evidence of the safety of HPV vaccines."

To know more about the session Vaccines Development in the conference STD 2018, visit:

Friday, 11 May 2018

HPV Vaccination Associated with Multiple Sclerosis

There is no significant association between the human papillomavirus (HPV) vaccination and multiple sclerosis, despite concerns over its propensity to cause the development of central nervous system autoimmune disorders, according to findings in a systematic literature review published in Human Vaccines & Immunotherapeutics.

The literature review identified relevant articles from a search performed in 5 different search engines:, Google Scholar, ISI Web of Knowledge, Medline, and Scopus. From this search, 15 different publications met established criteria during evaluation to be utilized for the qualitative synthesis. Of these publications, 1 pooled randomized clinical trial analysis, 5 were observational studies, and 9 were reviews. Of the 5 observational studies, 2 were case-control studies and 3 were cohort studies. Of the reviews, 2 were systematic and 7 were narrative.


The review of the cohort studies revealed that the relative risk for multiple sclerosis onset ranged from 1.54 (95% CI, 0.04-8.59) to 1.37 (95% CI, 0.74-3.20). In case-control studies, for the group exposed to the HPV vaccination, the odds ratio ranged from 0.3 (95% CI, 0.1- 0.9) to 1.60 (95% CI, 0.79-3.25). Neither of these results is significant, indicating that there is not a strong connection between multiple sclerosis onset and the HPV vaccination.

This literature review was conducted in response to the controversial nature of the correlation between the HPV vaccination and the development of central nervous system autoimmune disorders. Although the review shows no significant association between the vaccine and multiple sclerosis, the research is limited and cannot be generalized across all instances of central nervous system autoimmune disorders.

Further research should be conducted to determine whether these findings continue to hold validity across the entire pattern of central nervous system autoimmune disorders.



Meggiolaro A, Migliara G, La Torre G. Association between human papilloma virus (HPV) vaccination and risk of multiple sclerosis: a systematic review [published online January 15, 2018]. Hum Vaccin Immunother. doi:10.1080/21645515.2017.1423155

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New Possibility towards Cure for HIV

A research team led by scientists at AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine of The University of Hong Kong (HKU) have invented a universal antibody drug against HIV/AIDS which is another promising development towards cure for HIV.
Published in The Journal of Clinical Investigation, the team engineered a neutralising antibody, universally effective "not only against all genetically divergent global HIV-1 strains tested but also promoting the elimination of latently infected cells in a humanised mouse model."

AIDS remains an incurable disease. In the world, HIV/AIDS has resulted in estimated 40 million deaths while 36.9 million people are still living with the virus. To end the HIV/AIDS pandemic, it is important to discover either an effective vaccine or a therapeutic cure.
There are, however, two major scientific challenges: the tremendous HIV-1 diversity and the antiviral drug-unreachable latency.
Since it is extremely difficult to develop an appropriate immunogen to elicit broadly neutralising antibodies (bnAbs) against genetically divergent HIV-1 subtypes, developing existing bnAbs as passive immunisation becomes a useful approach for HIV-1 prophylaxis and immunotherapy.
Previous studies have investigated the potency, breadth and crystal structure of many bnAbs including their combination both in vitro and in vivo.
Naturally occurring HIV-1 resistant strains, however, are readily found against these so-called bnAbs and result in the failure of durable viral suppression in bnAb-based monotherapy.
To improve HIV-1 neutralisation breadth and potency, bispecific bnAb, which blocks two essential steps of HIV-1 entry into target cells, have been engineered and show promising efficacy in animal models.
Before the publication, tandem bi-specific bnAb has not been previously investigated in vivo against HIV-1 infection.
The accumulated number of HIV-1 infections has more than doubled from 4,443 diagnostic cases in 2009 to 9,091 in 2017, despite the timely introduced combination antiretroviral therapy and prevention interventions in Hong Kong alone.
Currently, the estimated annual cost is over HK$550 million for antiretroviral drugs alone per year in Hong Kong, not to mention the rising issues of life-long financial burdens, drug toxicity and resistant viruses.
The newly invented universal antibody drug brings the hope to fight these issues. With significantly improved breadth and potency, BiIA-SG will hopefully be the first "Made in Hong Kong" anti-HIV-1 antibody drug for clinical development.


Thursday, 10 May 2018

Sexually Transmitted Diseases Co-Infections

Chlamydia & Gonorrhoea Co-infection

Co-infection is the outcome of contracting a second STD while already actively infected with an STD. The most common use of the term co-infection is in reference to Gonorrhoea and chlamydia, which often occur together. The two infections are discovered together so often that it is actually recommended to get tested for both at the same time. Data released by the Virgina Department of Health supports the estimate that between 40 and 50 percent of all young adults infected with Gonorrhoea also have a chlamydia infection, with women more likely to have a co-infection than men. The risk of testing positive for both chlamydia and Gonorrhoea also increased when the use of drugs or alcohol was reported. Both chlamydia, which is caused by the Chlamydia trachomatis bacteria, and Gonorrhoea, caused by Neisseria gonorrhoeae bacteria, can be treated with antibiotics. If the infection is caught early enough, sometimes only a single dose of antibiotics is needed.

HIV Co-infections

Human immunodeficiency virus (HIV) is an incurable viral infection that attacks the immune system, destroying the infected person’s ability to fight off infection and disease. People living with HIV run a much higher risk of suffering from an STD co-infection than the HIV-negative community. The amount of HIV found in the genital secretions, known as the viral load, is much higher in people with an active STD infection. If HIV is left untreated, it progresses into the terminal late-stage known as Acquired Immune Deficiency Syndrome (AIDS). By the time HIV becomes AIDS, the patient has lost so much immune capability that they are extremely susceptible to infections, including STDs. Approximately 25% of people with HIV will also suffer from tuberculosis, which is the second highest cause of death for people living with HIV/AIDS. HIV co-infection is a serious and life-threatening condition that can be prevented.

HIV and Syphilis

HIV and syphilis have a long history of co-infection. According to a report conducted by the state of Virginia, approximately one-third of all new cases of syphilis diagnosed in Virginia were in individuals who had previously been diagnosed with HIV. The rate of syphilis infection in the HIV-positive community is 118 times higher than the general population. Receptive anal sex is considered a high risk behavior for contracting STDs because of the ease of damaging anal tissue, which allows a path for STDs to move between bodies via sexual fluids, such as semen. For this reason, men who have sex with men are the most affected by HIV and syphilis co-infection, with the state of Virginia reporting that 99.5 percent of all HIV/syphilis co-infections were among males, with 90 percent of those males engaging in sex with another man.

HIV and Gonorrhoea

While gonorrhoea, known as “the clap,” and chlamydia are the most closely linked of all co-infections, gonorrhoea also has a close tie to HIV. According to data released by the Washington State Department of Health, approximately 6 percent of all people diagnosed with Gonorrhoea were already living with HIV. Developing an immunity to HIV medications, as well as the chance of contracting an antibiotic-resistant strain of Gonorrhoea make this combination of infections particularly serious.

HIV and Hepatitis C

The World Health Organization states that 170 million people have been diagnosed with hepatitis C in the past century, making it an epidemic on a larger scale than even HIV, which has resulted in about 79 million diagnoses since the start of the HIV Epidemic. Hepatitis C is an incurable infection that has many life-threatening side effects, such as liver failure, cirrhosis, and cancer. Hepatitis also makes it more difficult for the immune system to properly fight off infection, making it easier to also become infected with HIV. Antiviral medications are prescribed to treat hepatitis C, as well as HIV. The biggest factor in contracting HIV when an active hepatitis C infection is present is the patient’s behavior, which includes intravenous drug use or unprotected sex in many cases. Being diagnosed with hepatitis C while living with HIV is one of the criteria for receiving an AIDS diagnosis. About 25% of HIV-positive Americans also have hepatitis C.

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