Day: February 4, 2022

Categories : HIVTags :

Highly Virulent HIV Variant Discovered

On By ModernMedia
HIV invading a human cell
HIV invading a human cell: Credit NIH

A new, more virulent and more damaging HIV variant has been discovered in the Netherlands.

Viral mutations are a source of concern because they can affect transmissibility and other factors. There have been fears of this happening in HIV-1, and now a new, highly virulent HIV strain in the Netherlands has been identified in a study. The results are published today in Science.

Prior to antiretroviral treatment, individuals infected with the new “VB variant” (for virulent subtype B) showed significant differences compared with individuals infected with other HIV variants:

  • A viral load between 3.5 and 5.5 times higher.
  • A doubled rate of CD4 cell decline (the hallmark of immune system damage by HIV), placing them at risk of developing AIDS much more rapidly.
  • Increased risk of transmitting the virus to others.

Fortunately, individuals with the VB variant had similar immune system recovery and survival to individuals with other HIV variants. However, because the VB variant causes a faster drop in immune system strength, early diagnosis and treatment is critical.

Researching the mechanism that causes the VB variant to be more transmissible and damaging to the immune system could lead to new targets for next-generation antiretroviral drugs. The VB variant is characterised by many mutations spread throughout the genome, meaning that a single genetic cause cannot currently be identified

Lead author Dr Chris Wymant said: ‘Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.’

Senior author Professor Christophe Fraser added: ‘Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment. This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.’

The VB variant was first identified in 17 HIV positive individuals from the BEEHIVE project, an ongoing study which collects samples from across Europe and Uganda. Since 15 of these people came from the Netherlands, the researchers then analysed data from a cohort of over 6700 HIV positive individuals in the Netherlands. This identified an additional 92 individuals with the variant, from all regions of the Netherlands, bringing the total to 109.

The researchers estimate that the VB variant first arose during the late 1980s and 1990s in the Netherlands, spreading more quickly than other HIV variants during the 2000s. However its spread has been declining since around 2010. The research team believe that the VB variant arose in spite of widespread treatment in the Netherlands, not because of it, since effective treatment can suppress transmission.

Since individuals with the VB variant are demographically similar, the spread is likely due to the properties of the virus itself.

Source: University of Oxford

Categories : COVID VaccinesTags :

South African Biotech Company Replicates Moderna Vaccine

On By ModernMedia
Photo by Mat Napo on Unsplash

Afrigen Biologics and Vaccines, a South African biotechnology company, has nearly created a copy of Moderna’s COVID mRNA vaccine, without Moderna’s involvement, Nature reports.

The Cape Town-based company has so far made only microlitres of the vaccine, based on Moderna’s publicly available development data. This nevertheless is a success for a major initiative launched by the World Health Organization (WHO): a technology transfer hub meant to build vaccine manufacturing capacity in low- and middle-income countries.

During the COVID pandemic, the developers of mRNA vaccines, Moderna and Pfizer/BioNTech have sent more than 70% of their doses to wealthy nations. Meanwhile, millions of vaccine orders for southern hemisphere countries have been delayed. “Moderna and Pfizer-BioNTech’s vaccines are mainly still going to just the richest countries,” says Martin Friede, the WHO official coordinating the hub. “Our objective is to empower other countries to make their own.”

Much work needs to be done before Afrigen’s mRNA vaccine mimic can be distributed. But the WHO hopes that the process of creating it will lay the foundation for a more globally distributed mRNA vaccine industry in the future.

Gerhardt Boukes, chief scientist at Afrigen is proud to have helped complete this first step of the plan. Afrigen and its collaborators completed the process, beginning with mRNA encoding a modified portion of the SARS-CoV-2 coronavirus, and finishing by encapsulating it in a lipid nanoparticle that delivers the vaccine to cells. “We didn’t have help from the major COVID vaccine producers,” he says, “so we did it ourselves to show the world that it can be done, and be done here, on the African continent.”

When the mRNA hub was launched by the WHO in June 2021, Moderna, Pfizer and BioNTech did not respond to requests to help make their vaccines, so the WHO proceeded without their help. The Moderna vaccine was chosen to copy because there is more freely available data on it, and it has not vowed to enforce its patents.

The project started in late September, with a Wits University team spearheading the first step: making a DNA molecule that would serve as a template to synthesise the mRNA needed in the vaccine. While Moderna controversially patented this sequence, Stanford University researchers had deposited it into the online database Virological.org in March last year.

Patrick Arbuthnot, director of gene therapy research at Wits says, “We were not intimidated, because mRNA synthesis is a fairly generic procedure.” Despite delays in the shipment of raw materials, the team completed this process in ten weeks and sent vials of mRNA to Afrigen in early December.

Around this time, scientists worldwide emailed offers of assistance. Some were researchers at the US National Institutes of Health who had conducted foundational work on mRNA vaccines. Petro Terblanche, Afrigen’s managing director, said that it was “extraordinary”. “I think a lot of scientists were disillusioned with what had happened with vaccine distribution, and they wanted to help get the world out of this dilemma.”

On 5 January, Afrigen’s researchers accomplished another tricky part of the process: They encapsulated the mRNA in a fatty nanoparticle made of a mixture of lipids. Boukes says they haven’t yet used Moderna’s specific lipid mixture, but rather another one that was immediately available from the manufacturer of the machine that the laboratory uses to create lipid nanoparticles. They plan to use Moderna’s lipid mixture in the coming days, as soon as one last analytical instrument arrives. After that, the team will analyse the formulation to ensure that it is truly a near copy of Moderna’s vaccine.

Once a reliable copy is made, the next step is increasing production. Jason McLellan, a structural biologist at the University of Texas at Austin whose work was foundational to the development of several COVID vaccines, says he is not surprised that SA scientists seem to have copied Moderna’s vaccine, but he adds that scaling up production of that original shot required a lot of additional innovation by manufacturers.

For the next phase of the project, several southern hemisphere companies will learn from Afrigen and attempt to create batches of vaccines themselves, in preparation for animal testing. By end November, the WHO expects a Moderna clone to be ready for phase I trials in humans.

What happens beyond that is unclear. Moderna might choose to license its patent (lab research is usually not subject to patent rules), or alternatives may become available, such as next-generation mRNA vaccines that do not require ultracold storage.

Source: Nature

Categories : Obstetrics & GynaecologyTags :

Women in Labour Have Faster Gastric Emptying with an Epidural

On By ModernMedia
Photo by Jonathan Borba on Unsplash

A study published in Anesthesiology finds gastric emptying is substantially slower during labour – but somewhat faster in women who receive an epidural for anaesthesia.

There is an ongoing debate as to whether it’s safe for women to eat solid food during labour. Physician anaesthesiologists prefer that labouring women have an empty stomach because of the lower risk for aspiration of food in case general anaesthesia for a caesarean section becomes necessary.

“These results suggest anaesthesiologists should remain cautious about permitting solid food during labour, especially when epidural analgesia is not used,” according to the report by Lionel Bouvet, MD, PhD, and colleagues of Hospices Civils de Lyon, France. 

Researchers assessed gastric emptying rates in four groups of women: 10 who were non-pregnant, 10 who were pregnant at full term (around 39 weeks) but not in labour, 10 in labour without an epidural, and 10 in labour who received an epidural for labour pain. On an empty stomach, each woman ate a light meal of yoghurt. Ultrasound scans were then used to compare the rate of stomach emptying among the four groups.

Stomach emptying was delayed for women in labour without epidural, in line with previous studies. The rate of stomach emptying from 15 to 90 minutes after eating was 52% in non-pregnant women and 45% in pregnant women at full term, compared to 31% for labouring women who received an epidural and 7% for women in labour without an epidural.

With epidural analgesia, gastric emptying occurred much faster during labour than during labour without epidural analgesia. After 90 minutes, the stomach was empty in 3 out of 10 labouring women who received an epidural, compared to 0 of 10 women in labour who had not received an epidural. By 2 hours, the stomach was empty in 6 of the women who received an epidural, compared to just 1 woman without an epidural.

Although clinical practice varies, current guidelines of the ASA and Society for Obstetric Anesthesia and Perinatology (SOAP) state that “Solid foods should be avoided in laboring patients,” reflecting a concern over the risk of aspiration in case anesthesia and surgery are needed. This new study is one of the first to systematically compare the extent of gastric emptying delay during late pregnancy and childbirth and with versus without epidural labor analgesia.

The results confirm a “statistically and clinically significant” longer time to an empty stomach among women in labour. However for those receiving epidural analgesia, stomach emptying appears to occur faster. Based on their findings, Dr Bouvet and co-authors suggest that a light solid meal “could probably be allowed” for women in labour who are receiving epidural analgesia and considered at a low risk of caesarean section within at least the next two hours.

“The report by Dr Bouvet and colleagues enables us to rethink our current practice of fasting during childbirth,” commented Anesthesiology editor Yandong Jiang, MD., PhD. “It is desirable that women giving birth with an epidural do not have the additional stress of hunger, but instead be allowed to eat a light meal.”

This contrasts with the ASA/SOAP recommendation that women in labour should consume only clear liquids to prevent aspiration, noted Mark Zakowski, MD, FASA, chair of ASA’s Committee on Obstetric Anesthesia. “This study clearly shows that stomach emptying is quite a bit slower for women in labor, and that if they eat even a light meal of about 4 ounces [about 120g] of yogurt, many will still have food in their stomach a few hours later,” Dr Zakowski said. “Since the need for emergency caesarean may arise at any time, the current ASA/SOAP guideline of clear liquids only during labour seems justified.”

Source: American Society of Anesthesiologists