Therapeutic HIV vaccine achieves encouraging results

 A phase I/IIa clinical trial that the University of Oxford collaborated on has demonstrated that a T-cell therapeutic HIV vaccine was associated with better control of the virus rebound when antiretroviral therapy (ART) was temporarily withdrawn.

Researchers carrying out the AELIX-002 study, whose results have been published in Nature Medicine, reported that two fifths of participants without any genetic background associated with spontaneous HIV control were able to stay off ART for the six-month duration of the supervised ART pause.

The vaccine in the study—developed by AELIX Therapeutics—delivered the HIVACAT T-cell Immunogen (HTI) using a combination of DNA vector, modified vaccinia virus Ankara (MVA) vector and simian adenovirus vector ChAdOx1. The latter two vaccines were constructed at Oxford.

Tomáš Hanke, Professor of Vaccine Immunology at the Jenner Institute, Nuffield Department of Medicine, who leads on HIV vaccine development, said, "This result provides further encouragement that active immunization against HIV may be possible, slowing HIV replication, providing a window of treatment holidays for people living with HIV and eventually leading to HIV cure. T cells/T-cell vaccines are likely to play an important part in the final package for HIV cure and, perhaps, other advanced therapies for difficult diseases."

Participants received several rounds of vaccination before interruption of the antiretroviral treatment and weekly monitor of their viral load.

Among the 45 participants enrolled in the study, 41 reached the interruption phase and, of these, 26 received the vaccine and 15 received a placebo under a double-blinded trial design—neither the patients nor the researchers knew the patients' allocation until the study was completed.

Of those who had no protective genotypes, eight vaccine recipients were able to stay off ART, while all but one participant in the placebo group had to restart treatment before the end of the six-month treatment interruption.

Prof Hanke directs an HIV Vaccine Program at the Jenner Institute that aims to develop a vaccine strategy for induction of protective T cells focused on the vulnerable conserved regions of HIV and encompasses trials in the UK, Europe, the US and Africa, where his partners and he enhance research capacity and infrastructure.

More information: Lucia Bailón et al, Safety, immunogenicity and effect on viral rebound of HTI vaccines in early treated HIV-1 infection: a randomized, placebo-controlled phase 1 trial, Nature Medicine (2022). DOI: 10.1038/s41591-022-02060-2

https://medicalxpress.com/news/2022-11-therapeutic-hiv-vaccine-results.html

Infant head-shaping pillows are useless and dangerous to baby, FDA warns

 Infant head-shaping pillows are not approved by the U.S. Food and Drug Administration and should not be used, the agency warned Thursday.

The pillows can create an unsafe sleep environment for infants, potentially contributing to the risk of suffocation and death.

Marketed as changing an infant's head shape or symmetry or claiming to treat other medical conditions, they have no demonstrated benefit, the agency said in a news release.

"If you own an infant head-shaping pillow, throw it away; do not donate or give it to anyone else," the alert said. "Be aware that infant head shaping pillows are not safe or effective for preventing or treating flat head syndrome or other medical conditions."

In most cases, flat head syndrome will go away on its own as an infant grows up, the FDA said. It is not painful and it does not cause any developmental concerns. Using a head-shaping pillow may delay necessary medical evaluations and mask something more serious, such as craniosynostosis, where a developing infant's skull bones join together too early.

The U.S. National Institutes of Health and the American Academy of Pediatrics both recommend infants sleep on their backs in a bare crib on a flat—not inclined—surface without pillows, toys, soft objects or loose bedding.

These recommendations are intended to help reduce the risk of Sudden Unexpected Infant Death (SUID), a category that includes Sudden Infant Death Syndrome (SIDS).

Health care providers should discourage the use of infant head-shaping pillows and educate their patients about the risks, the FDA added.

Infant head-shaping pillows are typically small, with an indent or hole in the center designed to cradle the back of an infant's head while the infant lays face up.

Some do not have the indent and are rectangular-shaped.

The FDA has cleared caps, helmets or head bands to improve head symmetry or shape in infants and toddlers from 3 months to 18 months of age.

Some devices are also intended for infants from 3 to 18 months of age whose head shape has been surgically corrected, but who still have a moderate-to-severe flat head, the FDA said.

The agency said it has communicated its concerns about promotional materials to companies that make these pillows and will continue to monitor claims for these products.

More information: Stanford Medicine has more on flat head syndrome.

https://medicalxpress.com/news/2022-11-infant-head-shaping-pillows-useless-dangerous.html

Fecal microbial transplants unpredictable with no prior antibiotic treatment

 A fecal microbial transplant—giving a recipient fecal matter from a donor to change the recipient's gut microbial community in the colon—has been a successful last resort therapy for people with recurrent Clostridium difficile infection after multiple rounds of suppressive antibiotics have eliminated the recipient microbial community.

However, fecal microbial transplants have also been given to alter a recipient's metabolism to reduce obesity or alter immunity to fight cancer, and in those transplants recipients are not given suppressive antibiotics to eliminate the microbial community prior to the transplant. In these cases, the initial gut community after transplant is a consortium of donor and recipient microbes that have to compete as new microbial strains are introduced into an established community.

University of Alabama at Birmingham researchers now report in the journal PLOS One that there is a lack of predictability for fecal microbial transplants to change the gut microbial community to correspond to that of the donor when there is no preconditioning to reduce the recipient microbe community. This contrasts with the C. difficile fecal microbial transplants after suppressive antibiotic therapy, where stable long-term colonization of donor strains is seen as long as two years post-transplant.

"The practical translation of our analysis suggests the use of pre-fecal microbial transplant treatments to reduce recipient microbial communities to facilitate a donor microbial strain-dominated gut microbial community following fecal microbial transplant," said UAB researchers Hyunmin Koo, Ph.D., and Casey Morrow, Ph.D. "In addition, longitudinal sampling of individual fecal microbial transplant patients in combination with strain tracking analysis to monitor the status of the post-fecal microbial transplant microbial community would also be important to assess the stability and, ultimately, the success of the fecal microbial transplant."

Koo and Morrow analyzed metagenomic sequencing published by Davar et al. in Science in 2021, using two established strain tracking methods, the WSS strain-tracking method developed at UAB and the strain-level population genomics tool StrainPhlAn. WSS can detect whether a donor strain or recipient strain of a particular species of gut microbes is dominant after fecal microbial transplants, and StrainPhlAn provides a phylogenetic tree of donor-related microbes or recipient-related microbes.

The Davar group gave fecal microbial transplants from patients who responded to anti-PD-1 immunotherapy for melanoma to recipient patients who were resistant to the immunotherapy, since it had been seen that the composition of the gut microbiota correlates with efficacy of anti-PD-1 therapy in animal models and cancer patients. Six out of 15 patients benefited.

Koo and Morrow analyzed five fecal microbial transplants by the Davar group where the recipient microflora was sampled multiple times for as long as 535 days post-fecal microbial transplant. This published metagenomic data allowed a time-series strain tracking analysis.

The UAB researchers found that three Alistipes bacterial species and one Parabacteroides species all had patterns, post-fecal microbial transplant, of either dominant donor or dominant recipient strains in the feces.

In contrast, Bacteroides uniformis and Bacteroides vulgatus showed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. Adding further to the complexity, there were some instances of dominant strains of the two Bacteroides species that were unrelated to either the donor or the recipient strains. Also, one Bacteroides vulgatus strain showed a possible genetic recombination event between the donor and recipient strains.

"The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post-fecal microbial transplant provide new insights into the dynamics of the microbial community interactions with the recipients following fecal microbial transplant," Morrow said. "The result from our analysis has implications for the use of fecal microbial transplant to predictably change the biological functions of the gut community in metabolism and host immunity."

More information: Hyunmin Koo et al, Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains, PLOS ONE (2022). DOI: 10.1371/journal.pone.0274633

https://medicalxpress.com/news/2022-11-fecal-microbial-transplants-lack-prior.html

NBC Quietly Removes Report Claiming Paul Pelosi Walked Away From Police

 The Paul Pelosi attack continues to grow more bizarre by the day.

On Friday, sources familiar with the investigation told NBC News that when the police responded to the high-priority call, they had no idea they had been called to the Pelosi residence. What's more, Pelosi did not immediately declare an emergency or try to leave his home.

"After a ‘knock and announce,’ the front door was opened by Mr. Pelosi. The 82-year-old did not immediately declare an emergency or try to leave his home," reports NBC. Instead, Pelosi "began walking several feet back into the foyer toward the assailant and away from police."

What's more, Pelosi and attacker David DePape were reportedly alone for 30 minutes.

Of note, NBC News has deleted the clip from their Twitter feed and scrubbed it  from their website.

Meanwhile, a neighbor living across from the Pelosis who was awake when the assault took place didn't hear an alarm or anything unusual. 

"No, not a thing, and you know we were awake at that hour in the morning; my husband was awake. We didn’t even hear sirens," neighbor Sally McNulty told The Epoch Times.

McNulty, who has lived in the neighborhood for 20 years, said everything was quiet around the time of the 2 a.m. attack on Oct. 28.

“This is one of the quietest streets in the city,” she said. “You can hear a pin drop at night.”

McNulty said she doesn’t recall ever hearing the Pelosis’ alarm go off in the past, though she has occasionally heard others in the neighborhood.

She said that Paul Pelosi had no enemies she knew of and was well-liked.

Other neighbors declined to comment.

Marjorie Campbell, a former neighbor of the Pelosis for 10 years, told the Daily Mail she recalled fleets of black SUVs surrounding the house around the clock when she stayed there.

Everyone in the neighborhood has alarms on their windows, and if glass were smashed, an alarm would sound, she told the publication. Campbell recalled her computers getting scrambled by alleged security measures to protect the congresswoman.

Nancy Pelosi was at her Pacific Heights home, the site of the attack, on Nov. 2 while several dark SUVs were parked outside. Capitol Police were present, too, as were multiple San Francisco Police Department cars.

Paul Pelosi had surgery to address a skull fracture and other injuries at the Zuckerberg San Francisco General Hospital and Trauma Center, after 42-year-old David DePape allegedly fractured his skull with a hammer on Oct. 28.

DePape pleaded not guilty to an attempted murder charge during a brief appearance in San Francisco Superior Court on Nov. 1. -Epoch Times

As PJ Media reports,

Pelosi’s failure to call out for help or flee his home was a detail in the court filing that previously raised a red flag to me, and it seems that even NBC News finds it odd. “Why Pelosi didn’t try to flee or tell responding officers he was in distress is unclear,” NBC News’s Miguel Almaguer noted.

Nevertheless, the report suggested it was unknown whether Pelosi was already injured or what mental state he was in.

https://www.zerohedge.com/political/pelosi-did-not-declare-emergency-nbc-raises-questions-about-unexplained-30-minutes-during

New Dual Agonist Weight Loss Injection Impressive, But Early Days

 A novel glucagon-like peptide-1 (GLP-1)/glucagon dual receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma led to "impressive" weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, during an oral session at ObesityWeek^® 2022.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

This is "very promising data as an anti-obesity compound," said Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.

"Exciting Data," But Still Early Days

"This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety," Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told Medscape Medical News in an email.

"The degree of weight loss is impressive for a 16-week study," Bessesen, professor of medicine in the Division of Endocrinology, Metabolism and Diabetes at the University of Colorado, added. "The longer-term weight loss will likely be more."

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, "so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow up not long."

In addition, "the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide."

The next hurdle is the "need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time" before this drug potentially enters the marketplace.

The "bottom line" is that this potential new anti-obesity/diabetes drug is "very promising, but [it is] still a little early to say where it ultimately will go."

A1c Results Presented at EASD

To be included in this study, patients had to be 18 to 75 years old, have type 2 diabetes, a body mass index (BMI) of 25 to 50 kg/m², and A1c of 7% to 10%, and be stable on metformin therapy.

The patients had a mean age of 57 years and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

"We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering," Rosenstock said.

"It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin."

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the "gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related," Rosenstock said, "and it's highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events."

BI 456906 was co-invented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

ObesityWeek^® 2022. Abstract Oral-063. Presented November 3, 2022.

https://www.medscape.com/viewarticle/983542

CDC Officials 'Want Flexibility in Times of Crisis'

 Government restrictions hinder the CDC from doing the best possible job in a time of crisis, current and former agency officials are saying.

They're hoping to persuade Congress for greater flexibility and support. Despite its multibillion-dollar budget, the CDC is unauthorized to hire consultants in an urgent situation. 

Rochelle Walensky, director of the CDC, told CNN that she will ask Congress for flexibility to do that kind of hiring in a crisis. Other federal agencies already have that kind of authority.

Walensky said she hopes to "move the needle" by using "real-time examples of how public health has been hurt because of our inability to take action" during the COVID-19 pandemic.

"I want to be very clear that [we] are not asking for a blank-slate ability to release resources. What we're saying is, in certain situations, we need to be nimble and act urgently in culturally sensitive ways that we don't currently have the capacity to do," Walensky said.

Dr. Tom Frieden was CDC director from 2009 - 2017. He said the agency suffered from the same limitations in 2014 during the Ebola outbreak.

"If we want CDC to get better at fighting diseases, we need to stop tying their hands behind their back," he said. "This is the kind of torment of working within the government system." 

By comparison, the Federal Emergency Management Agency (FEMA) and the U.S. Agency for International Development (USAID) can make certain types of contractual arrangements with outside organizations, their spokespeople told CNN.

"We're not asking for money. We're asking for capacity. We're asking for authorities to be able to do our job," Walensky said. "[But] I don't know if I will be more successful than my predecessors."

https://www.medscape.com/viewarticle/983531

Deadly Monkeypox Variant Circulating In Central Africa

 

• Researchers have warned that a dangerous monkeypox variant with a fatality rate as high as 10% is circulating in Central Africa, which could trigger new global outbreaks.
• After analyzing 1,463 cases between 2013 and 2017, scientists have found that monkeypox transmission in a remote part of the Democratic Republic of the Congo is much higher than previously thought.
• Citing one of the CDC researchers behind the report, Forbes reported that transmission has been ”getting close to the point where it can cause large and sustained local outbreaks.”
• The World Health Organization declared monkeypox infection a global health emergency. In August, health officials said they are witnessing early signs of waning growth in infection rates in Europe and the U.S.
• The researchers also found evidence suggesting the monkeypox virus—believed to be harbored by rodents—is spilling over from animals into humans more frequently.
• The few shots and treatments used against monkeypox are available but in very short supply and have gone mainly to wealthy Western nations. 
• In September, the White House reportedly sought $3.9 billion to fight against monkeypox.
• The African communities that have struggled with monkeypox for years have received few vaccines and continue to be overlooked.

https://www.benzinga.com/general/biotech/22/11/29553026/threats-for-new-outbreak-looms-as-scientists-signal-deadly-monkeypox-variant-circulating-in-centr