Tag Archives: immune response

AstraZeneca’s COVID-19 Vaccine Produces An Immune Response in Older People

Immunogenicity responses similar between older and younger adults

One of the world’s leading COVID-19 experimental vaccines produces a immune response in both old and young adults, raising hopes of a path out of the gloom and economic destruction wrought by the novel coronavirus.  The vaccine, developed by the University of Oxford, also triggers lower adverse responses among the elderly, British drug maker AstraZeneca Plc AZN.L, which is helping manufacture the vaccine, said on Monday. A vaccine that works is seen as a game-changer in the battle against the novel coronavirus, which has killed more than 1.15 million people, shuttered swathes of the global economy and turned normal life upside down for billions of people.

It is encouraging to see immunogenicity responses were similar between older and younger adults and that reactogenicity was lower in older adults, where the COVID-19 disease severity is higher,” an AstraZeneca spokesman said.

https://uk.reuters.com

Why RNA Is A Better Measure Of A Patient’s Current Health Than DNA

By harnessing the combined power of NGS, machine learning and the dynamic nature of RNA we’re able to accurately measure the dynamic immune response and capture a more comprehensive picture of what’s happening at the site of the solid tumor. In the beginning, there was RNA – the first genetic molecule.

In the primordial soup of chemicals that represented the beginning of life, ribonucleic acid (RNA) had the early job of storing information, likely with the support of peptides. Today, RNA’s cousin – deoxyribonucleic acid – or DNA, has taken over most of the responsibilities of passing down genetic information from cell-to-cell, generation-to-generation. As a result, most early health technologies were developed to analyze DNA. But, RNA is a powerful force. And its role in storing information, while different from its early years, has no less of an impact on human health and is gaining more mindshare in our industry.

RNA is often considered a messenger molecule, taking the information coded in our DNA and transcribing it into cellular directives that result in downstream biological signals and proteinslevel changes.  And for this reason, RNA is becoming known not only as a drug target but perhaps more importantly, as a barometer of health.

3d illustration of a part of RNA chain from which the deoxyribonucleic acid or DNA is composed

How and why is RNA so useful? First, RNA is labile — changing in both sequence and abundance in response to genetic and epigenetic changes, but also external factors such as disease, therapy, exercise, and more. This is in contrast to DNA, which is generally static, changing little after conception.

Next, RNA is a more accurate snapshot of disease progression. When mutations do occur at the DNA level, these do not always result in downstream biological changes. Often, the body is able to compensate by repairing the mutation or overcome it by using redundancies in the pathway in which the gene resides. By instead evaluating RNA, we get one step closer to understanding the real impact disease is imparting on our body.

Finally, RNA is abundant. In most human cells, while only two copies of DNA are present, hundreds of thousands of mRNA molecules are present,representing more than 10,000 different species of RNA. Because even rare transcripts are present in multiple copies, biological signals can be confidently detected in RNA when the right technology is used.

Source: https://medcitynews.com/

Coronavirus: Russian vaccine shows signs of immune response

Russian scientists have published the first report on their coronavirus vaccine, saying early tests showed signs of an immune response.
The report published by medical journal The Lancet said every participant developed antibodies to fight the virus and had no serious side effects. Russia licensed the vaccine for local use in August, the first country to do so and before data had been published.

Experts say the trials were too small to prove effectiveness and safety. But Moscow has hailed the results as an answer to critics. Some Western experts have raised concerns about the speed of Russia’s work, suggesting that researchers might be cutting corners.

Last month, President Vladimir Putin said the vaccine had passed all the required checks and that one of his own daughters had been given it. Two trials of the vaccine, named Sputnik-V, were conducted between June and July, The Lancet paper said. Each involved 38 healthy volunteers who were given a dose of the vaccine and then a booster vaccine three weeks later.
The participants – aged between 18 and 60 – were monitored for 42 days and all of them developed antibodies within three weeks. Among the most common side effects were headaches and joint pain. The trials were open label and not randomised, meaning there was no placebo and the volunteers were aware they were receiving the vaccine.

https://www.bbc.com/

China confirms Its First COVID-19 Vaccine Patent

China, ground zero of the novel coronavirus outbreak, confirmed its first COVID-19 vaccine patent Sunday, according to state-affiliated media. “China has approved its first COVID19 vaccine patent, which has been developed by PLA infectious disease expert Chen Wei’s team. Earlier, the phase 2 trial of the vaccine candidate found that the vaccine is safe and induces an immune response, China Global Television Network (CGTN) said on Twitter. Citing data from clinical trials published in the Journal of the American Medical Association (JAMA), China’s state-run Xinhua News Agency reported earlier in the day that the COVID-19 vaccine candidate is “safe and generates an immune response.”

 The COVID-19 vaccine candidate is “safe and generates an immune response,” reported China’s state-run Xinhua News Agency.

The research involved 320healthy volunteers” aged between 18 and 59, of which 96 participated in phase-1 clinical trials and 224 in phase-2 trials, it said. Xinhua said the results indicated that the vaccine effectively induced neutralizing antibodies in the volunteers and demonstrated good ability of a substance to trigger an immune response. On Saturday, Russia’s Health Ministry announced that the country has started production of its first COVID-19 vaccine, noting initial batches will be earmarked for immunizing doctors and health workers before going to the general public. Russia officially registered the world’s first coronavirus vaccine, developed by the Gamaleya Research Institute of Epidemiology and Microbiology, on Tuesday.

Source: https://jamanetwork.com/
AND
https://fr.reuters.com/

Novavax’s Coronavirus Vaccine Generates Promising Immune Response

Novavax announced Tuesday that its potential vaccine to prevent Covid-19 generated a promising immune response in an early stage clinical trial, but the biotech company’s stock fell briefly on concerns about its safety.

The phase one trial included 131 healthy participants between the ages 18 and 59 at two sites in Australia. Novavax said 106 participants received one of four dose levels of the potential vaccine, named NVX-CoV2373, with or without an adjuvant, which is an ingredient designed to enhance the immune response. The remaining 25 patients received a placebo. Participants received two doses of the potential vaccine via intramuscular injection approximately 21 days apart, the company reported. The vaccine produced neutralizing antibodies, which researchers believe are necessary to build immunity to the virus, and killer T-cells, the company said. Additionally, the neutralizing antibodies that were produced were higher than those seen in people who have recovered from Covid-19, Novavax underscored. The immune response was also stronger for those who had the adjuvant, the company said.

Novavax explained that the vaccine was well tolerated with no serious adverse events reported. Most patients reported tenderness and pain at the injection after the first dose, with some patients also reporting headaches, fatigue or muscle aches. Only one participant in the trial experienced a mild fever after a second dose, the company noted. Earlier media reports and analysts cited eight possible hospitalizations related to the study, but the company said no patients were hospitalized.

https://www.cnbc.com/

China’s Phase 2 Trial Finds COVID-19 Vaccine Safe, Inducing Immune Response

A phase 2 trial of a COVID-19 vaccine candidate conducted in China has found that the vaccine is safe and induces an immune response, according to a new study published Monday in medical journal The Lancet.
The results provide data from a wider group of participants than the phase 1 trial, which was published in May. Phase 1 trial involved 108 healthy adults and it demonstrated promising results.

The phase 2 trial adds further evidence on safety and immunogenicity in a large population than the phase 1 trial. This is an important step in evaluating this early-stage experimental vaccine and phase 3 trials are now underway,” said Professor Fengcai Zhu from Jiangsu Provincial Center for Disease Control and Prevention, China.
According to The Lancet, the trial of the Ad5 vectored COVID-19 vaccine candidate was conducted in the central Chinese city of Wuhan with 508 participants taking part. Approximately two thirds of participants were aged 18-44 years, with a quarter aged 45-54 years, and 13 percent aged 55 years or older.
http://www.xinhuanet.com/

Personalized microrobots swim through biological barriers, deliver drugs to cells

Tiny biohybrid robots on the micrometer scale can swim through the body and deliver drugs to tumors or provide other cargo-carrying functions. The natural environmental sensing tendencies of bacteria mean they can navigate toward certain chemicals or be remotely controlled using magnetic or sound signals.

To be successful, these tiny biological robots must consist of materials that can pass clearance through the body’s immune response. They also have to be able to swim quickly through viscous environments and penetrate to deliver cargo.

In a paper published this week in APL Bioengineering, from AIP Publishing, researchers fabricated biohybrid bacterial microswimmers by combining a genetically engineered E. coliMG1655 substrain and nanoerythrosomes, small structures made from red cells.

Illustration (top) and scanning electron microscopy image (bottom) of biohybrid bacterial microswimmers, which were fabricated by combining genetically engineered E. coliMG1655 and nanoerythrosomes made from red blood cells. A biotin-streptavidin interaction was used to attach nanoerythrosomes to the bacterial membrane.

Nanoerythrosomes are nanovesicles derived from red blood cells by emptying the cells, keeping the membranes and filtering them down to nanoscale size. These tiny red blood cell carriers attach to the bacterial membrane using the powerful noncovalent biological bond between biotin and streptavidin. This process preserves two important red blood cell membrane proteinsTER119 needed to attach the nanoerythrosomes, and CD47 to prevent macrophage uptake.

The E. coli MG 1655 serves as a bioactuator performing the  of propelling through the body as a molecular engine using flagellar rotation. The swimming capabilities of the bacteria were assessed using a custom-built 2-D object-tracking algorithm and 20 videos taken as raw data to document their performance.

Biohybrid microswimmers with bacteria carrying red blood cell nanoerythrosomes performed at speeds 40% faster than other E. coli-powered microparticles-based biohybrid microswimmers, and the work demonstrated a reduced immune response due to the nanoscale size of the nanoerythrosomes and adjustments to the density of coverage of nanoerythrosomes on the bacterial membrane.

These biohybrid swimmers could deliver drugs faster, due to their swimming speed, and encounter less immune response, due to their composition. The researchers plan to continue their work to further tune the immune clearance of the microrobots and investigate how they might penetrate and release their cargo in the tumor microenvironment.

Source: https://aip.scitation.org/

Personalized cancer vaccines

Therapeutic cancer vaccines were first developed 100 years ago and have remained broadly ineffective to date. Before tangible results can be achieved, two major obstacles must be overcome. Firstly, since tumor mutations are unique to each patient, cancer cell antigens must be targeted extremely precisely, which is very hard to achieve. Secondly, a safe system is needed to deliver the vaccine to the right location and achieve a strong and specific immune response.

Li Tang’s team at EPFL’s School of Engineering in Switzerland is coming up with a solution to the delivery problem. The researchers have used a polymerization technique called polycondensation to develop a prototype vaccine that can travel automatically to the desired location and activate immune cells there. The patented technique has been successfully tested in mice and is the topic of a paper appearing in ACS Central Science. Li Tang has also co-founded a startup called PepGene, with partners that are working on an algorithm for quickly and accurately predicting mutated tumor antigens. Together, the two techniques should result in a new and better cancer vaccine in the next several years.

Helping the body to defend itself

Most vaccines – against measles and tetanus for example – are preventive. Healthy individuals are inoculated with weakened or inactivated parts of a virus, which prompt their immune systems to produce antibodies. This prepares the body to defend itself against future infection.

However, the aim of a therapeutic cancer vaccine is not to prevent the disease, but to help the body defend itself against a disease that is already present. “There are various sorts of immunotherapies other than vaccines, but some patients don’t respond well to them. The vaccine could be combined with those immunotherapies to obtain the best possible immune response,” explains Li Tang. Another advantage is that vaccines should reduce the risk of relapse.

Delivering a cancer vaccine to the immune system involves various stages. First, the patient is inoculated with the vaccine subcutaneously. The vaccine will thus travel to the lymph nodes, where there are lots of immune cells. Once there, the vaccine is expected to penetrate dendritic cells, which act as a kind of alert mechanism. If the vaccine stimulates them correctly, the dendritic cells present specific antigens to cancer-fighting T-cells, a process that activates and trains the T-cells to attack them.

The procedure appears simple, but is extremely hard to put into practice. Because they are very small, the components of a vaccine tend to disperse or be absorbed in the blood stream before reaching the lymph nodes.

To overcome that obstacle, Li Tang has developed a system that chemically binds the vaccine’s parts together to form a larger entity. The new vaccine, named Polycondensate Neoepitope (PNE), consists of neoantigens (mutated antigens specific to the tumor to be attacked) and an adjuvant. When combined within a solvent, the components naturally bind together, forming an entity that is too large to be absorbed by blood vessels and that travels naturally to the lymph nodes.

Source: https://actu.epfl.ch/news/

Micromotors Deliver Oral Vaccines

Researchers are working on new generations of oral vaccines for infectious diseases. But to be effective, oral vaccines must survive digestion and reach immune cells within the intestinal wall. As a step in this direction, UC San Diego nanoengineering researchers have developed oral vaccines powered by micromotors that target the mucus layer of the intestine.

The work appears in the ACS journal Nano Letters. It’s a collaboration between the labs of nanoengineering professors Joseph Wang and Liangfang Zhang at the UC San Diego Jacobs School of Engineering.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

The lack of needles is one reason oral vaccines are attractive. Another reason: oral vaccines can generate a broad immune response by stimulating immune cells within the mucus layer of the intestine to produce a special class of antibody called immunoglobulin A (IgA). The NanoLetters paper documents the team’s efforts to use magnesium particles as tiny motors to deliver an oral vaccine against the bacterial pathogen Staphylococcus aureus. When coated over most of their surfaces with titanium dioxide, magnesium microparticles use water as fuel to generate hydrogen bubbles that power their propulsion.

To develop the oral vaccine, the researchers coated magnesium micromotors with red blood cell membranes that displayed the Staphylococcal α-toxin, along with a layer of chitosan to help them stick to the intestinal mucus. Then, they added an enteric coating that protects drugs from the acidic conditions of the stomach.

The micromotors safely passed through the stomach to the intestine, at which point the enteric coating dissolved, activating the motors. Imaging of mice that had been given the vaccine showed that the micromotors accumulated in the intestinal wall much better than non-motorized particles. The micromotors also stimulated the production of about ten times more IgA antibodies against the Staphylococcal α-toxin than the static particles.

Source: http://jacobsschool.ucsd.edu/