DS-Cav1 RSV Vaccine

Longhorn & NIH Leading Innovative RSV Vaccine Study

Don Hackett — Thu, 01 Aug 2019 20:06:34 +0000

Reviewer:

According to a University of Texas (UT) at Austin announcement, an experimental vaccine against the Respiratory Syncytial Virus (RSV) has shown early promise in a Phase 1 clinical study.

A team of researchers, including UT Austin’s associate professor Jason McLellan, Ph.D., reported on August 1, 2019, that an interim analysis showed that 1-dose of the DS-Cav1 (VRC317) vaccine candidate elicited large increases in RSV-neutralizing antibodies that were sustained for several months.

This is good news since there is not a commercially available preventive vaccine nor antivirals for treating patients with RSV.

These researchers found that the DS-Cav1 vaccine candidate elicits a greater than 10-fold increase in RSV-neutralizing antibodies, compared with the number of antibodies a person produces naturally from RSV exposure earlier in life.

This new report data is from the first 40 healthy adult volunteers enrolled in the trial, which began at the National Institutes of Health (NIH) Clinical Center in 2017.

Scientists have tried to create an RSV vaccine for more than 50 years. But, Dr. McLellan and his colleagues took a new, innovative approach, called ‘structure-based vaccine design.’

It was already known that a certain part of RSV, called the F protein, triggers the human immune system to produce antibodies. But the F protein is a shapeshifter — before it infects a cell, it takes one shape and then during infection, it shifts to a second shape.

If the immune system encounters an RSV virus with the F protein in the first shape, it makes potent antibodies.

But if the protein is in the second shape, fewer antibodies are elicited, and they are not very effective.

Producing RSV vaccines using traditional methods usually leads to F proteins in the second shape and poor antibody response.

This is where the ‘structure-based approach’ comes in.

First, the researchers used a technique called X-ray crystallography to determine the atomic-level structure of the F protein in the first shape. Next, they re-engineered the F protein to take away its shape-shifting ability, locking it in the shape that elicits the best antibodies.

In 2013, these researchers tested several versions as a vaccine in both mice and nonhuman primates. These protein variants elicited high-levels of neutralizing antibodies and protected the animals against RSV infection.

“Our first time testing these stabilized molecules in animals, the response was 10-fold higher than anything anyone had ever seen before,” Dr. McLellan said in a press release.

“And at that point, we’re thinking, ‘This is it. We’ve got it.’ That was exciting.”

The most promising of these vaccine candidates, DS-Cav1, was selected for clinical evaluation and subsequently manufactured by the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC).

The results are promising, but Dr. McLellan is careful to put them in perspective.

“The Phase 1 study just asks: Is it (vaccine) safe and is it eliciting the types of antibodies and response that we were hoping to see?” he said. “It still needs to go through Phase 2 and Phase 3, looking at efficacy such as, is it reducing the severity of the disease, or is it reducing hospitalizations?”

Dr. McLellan says, “If it works reasonably well and we prevent 70 to 80 percent of all deaths, just think of all the little infants and toddlers we’d save.”

“There aren’t that many vaccines in the world, and so if we’re able to actually participate in making one that works and saves lives, that would be awesome,” said Dr. McLellan.

RSV news

RSV is very dangerous to the very young and the very old, causing pneumonia, bronchiolitis and other lower respiratory tract diseases, says the Centers for Disease Control and Prevention (CDC).

Furthermore, almost all children will have had an RSV infection by their second birthday.

Most RSV infections go away on their own in a week or two. People can manage the related fever and pain with over-the-counter fever reducers and pain relievers, such as acetaminophen or ibuprofen.

Healthy infants and adults infected with RSV do not usually need to be hospitalized. But, every year, millions of people become sickened by RSV, causing more than 100,000 fatalities worldwide, says the CDC.

Final results of this phase 1 trial are expected in 2020.

Barney Graham and Peter Kwong of the NIH’s National Institute of Allergy and Infectious Diseases’ Vaccine Research Center (VRC), along with Dr. McLellan, spearheaded the development of the vaccine candidate DS-Cav1.

The University of Texas at Austin is committed to transparency and disclosure of all potential conflicts of interest. The university investigator involved in this research, Jason McLellan, has submitted required financial disclosure forms with the university. McLellan is an inventor on several patent applications related to this research filed by the National Institutes of Health, from which he is receiving royalties.

Sub Title:

DS-Cav1 vaccine candidate elicited large increases in RSV-neutralizing antibodies sustained for several months

References:

A proof of concept for structure-based vaccine design targeting RSV in humans

Dose, Safety, Tolerability and Immunogenicity of a Stabilized Prefusion RSV F Subunit Protein Vaccine DS-Cav1,Alone or With Alum

Experimental Vaccine Against Respiratory Syncytial Virus (RSV) Elicits Strong Immune Response

Experimental respiratory syncytial virus vaccine prompts antibody surge

CDC: Respiratory Syncytial Virus Infection (RSV) Symtoms and Care

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health, vaccines, vaccinations, rsv vaccine, vaccine to prevent infants getting rsv, new rsv vaccine

Featured:

When Are Infants Most Vulnerable to Asthma?

Don Hackett — Thu, 06 Dec 2018 19:39:50 +0000

Reviewer:

Robert Carlson, MD

Danielle Reiter, RN

Infants who contract severe respiratory syncytial viral (RSV) disease after the age of 6 months are twice as likely to develop severe asthma in later years, says a new study.

These authors believe this new study should inform how to implement the immunization against RSV to boost immunity beyond the reach of the maternal vaccine.

This study was the 1st to examine at what age an infant is most vulnerable to developing asthma, after a severe bout of RSV.

This news is important since almost all children will be infected with RSV by their 2nd birthday, says the Centers for Disease Control and Prevention (CDC).

RSV is the most common cause of bronchiolitis and pneumonia in children younger than 1 year of age in the United States.

Approximately 57,000 children younger than 5 years old are hospitalized due to RSV infection each year.

This new study of hospitalized babies due to RSV over a 10-year period was published in the Journal of Infectious Diseases, on December 4, 2018.

RSV is the leading cause of lower respiratory tract infections like bronchiolitis in infants.

Moreover, early RSV disease is also a strong predictor of future childhood asthma.

**Suffering from Asthma? Click here for a clinical trial**

Dr. Nusrat Homaira, from the School of Women’s & Children’s Health, at the University of New South Wales, said in a press release, ‘the research has important implications for the development and implementation of a promising vaccine.’

“In the last 10 years, there has been unprecedented development of a vaccine for RSV because it's such a huge problem.”

Dr. Homaira said “80 percent of infants get the RSV disease by their 2nd birthday.’

“The vaccine under development is going to be given to women during their third trimester to boost the maternal antibodies, which will protect babies against severe RSV.”

However, Dr. Homaira says ‘protection from a ‘passive’ vaccine administered to an expectant mother may only protect as far as 6 months into the baby’s life following birth.’

‘After this time, an infant could still develop an RSV infection.’

Dr. Homaira and her co-authors looked at 18,042 children with severe RSV disease who were hospitalized in their first 2 years of life in NSW between 2001 and 2010 and saw two interesting patterns emerge.

First, 60 percent of all hospital admissions were for infants aged 6 months or younger.

“This confirmed that there is a very good reason to develop the maternal vaccine because it is going to protect them in the first six months of their life,” Dr. Homaira says.

But, the 2nd finding was one that surprised the research team.

Contrasted with the study cohort of infants who contracted RSV in their first six months of life, the 40 percent of children hospitalized after the age of 6 months more went on to return to the hospital with severe asthma in later years.

“So what our analysis showed is that even though there are more severe RSV cases in the first 6 months of life, if severe RSV is after 6 months of age, the rate of subsequent asthma is actually higher in those children.”

“While the maternal vaccine is extremely important for our children, we also need an active vaccination strategy or an active vaccine candidate that is going to protect children in the first 2 years of life,” Dr. Homaira says.

Recent RSV vaccine news:

In a previous study, Dr. Homaira looked at the rate of asthma in children who had been hospitalized from RSV in their first two years and those who hadn’t. That study concluded that the first group was twice as likely to develop asthma than those children who hadn’t had severe RSV.

“This is a novel study, there is nothing published in this space which has looked at this specific analysis.”

“So one of our conclusions in the paper is there is a need for further study in other settings to validate what we have found out,” said Dr. Homaira.

Sub Title:

Children with RSV disease after the age of 6 months are twice more likely to develop severe asthma in later years