Culture-Negative Fibrinous Peritonitis in a Postpartum Female

'Game Changer': LSU Professor Develops Vaccine For Virus That Kills Millions Of Calves A Year

Bulls and cows can survive an illness called bovine respiratory disease, but it can be fatal to calves, killing about 8 million of them every year in the U.S.

A new vaccine developed by an LSU veterinary medicine professor will be a game changer, the university said.

What makes bovine respiratory disease particularly dangerous is that the complex of viruses that cause it can stay in cells near the brain and return at will, said Shafiqul Chowdhury, Ph.D., who has spent the past decade developing a vaccine that can stop the disease.

"The virus enters through the animal's nose, creeps along the nerves and enters nerve fibers and cell bodies close to the brain," Chowdhury said. "This virus sits in the nucleus for life and can come back." 

With his vaccine, "it will sit there and never come out," he said this week in a phone interview. 

Symptoms of the disease, often fatal to calves, are fever, lethargy, lack of appetite, and a cough, as well as rapid, shallow breathing. 

A current vaccine used by the cattle industry against bovine respiratory disease is made up of several live viruses — and variants of those viruses are thought to be the cause of cases of bovine respiratory virus even in animals that have been vaccinated, LSU said in a news release. 

For the new vaccine, Chowdbury took the initial virus that causes the disease — bovine herpes type 1, which suppresses the animal's immune system — and genetically modified it to provide the protective proteins of other bovine respiratory viruses.

"Our vaccine is safer for calves and far more effective than the vaccine 'cocktail,'" now in use, he said.

Chowdhury has applied for a patent for the vaccine with the help of LSU's Office of Innovation and Technology Commercialization, which protects and commercializes LSU's intellectual property.

A company has also signed a licensing agreement with LSU to sell the vaccine in the future, Chowdhury said. 

"I will continue the research," he said. "In another five years, we'll have an even better vaccine." 

The Covid-19 Pandemic Killed Off One Strain Of The Flu, And That Will Change The Next Vaccines

CNN  — 

For 10 years, Americans have had access to flu shots that protect against four strains of the virus: two A strains and two B strains.

Starting this fall, however, all the flu shots distributed in the United States will contain only three strains, and the change happened in part because of Covid-19.

On Tuesday, a panel of experts who advise the US Food and Drug Administration on vaccines voted unanimously to recommend three-strain flu vaccines that will exclude any viruses from B strains that are part of branch of the flu's family tree called Yamagata.

Yamagata viruses were in decline before the pandemic, and all the precautions that helped people avoid Covid-19 – including masking, staying at home and better ventilation – appear to have finished them off. They haven't been detected in testing since March 2020.

One Yamagata strain was typically included in each year's flu shot recipe, so vaccine designers faced a quandary this year: Should they drop the strain from the formula or keep it in, since B-viruses are known to be cagey?

In the 1990s, when Yamagata was in its heyday, another branch of B-strain flu viruses called Victoria was seen only sporadically in testing, but it had a resurgence in the 2000s. What if Yamagata came back after a lengthy absence? It's not quick or easy to change how flu vaccines are manufactured, and those changes require regulatory review and approval.

Related article Moderna says mRNA flu shot generates better immune response in study than currently available vaccine

In September, the World Health Organization said that "inclusion of the Yamagata-lineage antigens in influenza vaccines is no longer warranted," and in October, the FDA's vaccine experts also said the Yamagata strains should be dropped as quickly as possible.

"We've been talking about this for four years," said Dr.Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia and a member of the FDA's Vaccines and Biological Products Advisory Committee, or VRBPAC.

The change is happening faster than expected, said Dr. Arnold Monto, another VRBPAC member. He noted that in October, when the committee first voted to recommend removing Yamagata from flu vaccines, they were told that it might be impossible to exclude it next season because of regulatory red tape.

Dr. Jerry Weir, director of the FDA's Division of Viral Products, said Tuesday that the agency has been working with manufacturers to get the Yamagata strain out of US vaccines in time for the 2024-25 flu season.

"At this point in time, each of the US influenza vaccine manufacturers have submitted updated regulatory files related to a trivalent influenza vaccine, and approval of all the necessary regulatory submissions is on track for 2024-25" season, he said during the advisory committee's meeting.

In fact, Weir noted, the US was able to move faster than some other countries because all the vaccine manufacturers already had approvals for trivalent flu vaccines here. It's taking longer in other parts of the world to make the switch.

For that reason, the committee also voted to recommend a four-strain formula – including one from B/Yamagata – for vaccines that will be manufactured in the US but distributed in other countries.

"And I think we should congratulate both FDA and the manufacturers of making this possible, because the problem seems to be totally logistic," Weir said.

There are good reasons for dropping the Yamagata strain, Offit said.

"You don't want to be vaccinating people for something they don't need," he said.

There may also be some harms in continuing to include it, said Dr. Jodie Guest, senior vice chair of the Department of Epidemiology at Emory University's Rollins School of Public Health, who is not a member of the FDA committee.

"Anytime these flu vaccines are being produced, they are – depending on which vaccines you are talking about – using live or attenuated virus, and you do have to grow it," she said. Growing something in a lab also means it could escape from that lab.

"So while it would be an anticipated, incredibly small risk, there is the possibility you could reintroduce it into the population by having it contained in a vaccine," Guest said.

Other researchers have pointed out that dropping the Yamagata strain would free up production capacity to increase the number of doses made globally, something that would benefit countries affected by shortages.

In an article on the expected changes published February 28 in the New England Journal of Medicine, Monto, Weir and Dr. Maria Zambon from the UK Health Security Agency said the move opens the door to considering new vaccine formulas.

Since the shot's B/Victoria and A/H1N1 strains are often more effective than the A/H3N2 component, some experts have suggested doubling the dose of H3N2 or perhaps slipping in a second member of that family.

But as the authors note, any such change would require testing and regulatory approval, and for that reason, it's not likely we'll see the return of four-strain flu shots very quickly. Instead, they say, it will be "more of a long-term goal for improving vaccine effectiveness."

In the meantime, scientists will keep testing flu viruses, just to make sure Yamagata really has been relegated to the history books.

Nanoparticle Discovery Could Make Vaccines More Powerful

Many vaccines, including vaccines for hepatitis B and whooping cough, consist of fragments of viral or bacterial proteins. These vaccines often include other molecules called adjuvants, which help to boost the immune system's response to the protein.

Most of these adjuvants consist of aluminum salts or other molecules that provoke a nonspecific immune response. A team of MIT researchers has now shown that a type of nanoparticle called a metal organic framework (MOF) can also provoke a strong immune response, by activating the innate immune system — the body's first line of defense against any pathogen — through cell proteins called toll-like receptors.

In a study of mice, the researchers showed that this MOF could successfully encapsulate and deliver part of the SARS-CoV-2 spike protein, while also acting as an adjuvant once the MOF is broken down inside cells.

While more work would be needed to adapt these particles for use as vaccines, the study demonstrates that this type of structure can be useful for generating a strong immune response, the researchers say.

"Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines," says Ana Jaklenec, a principal investigator at MIT's Koch Institute for Integrative Cancer Research and one of the senior authors of the new study.

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Subscribe for FREE Robert Langer, an MIT Institute Professor and member of the Koch Institute, and Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School, are also senior authors of the paper, which appears today in Science Advances. The paper's lead author is former MIT postdoc and Ibn Khaldun Fellow Shahad Alsaiari. Immune activation

In this study, the researchers focused on a MOF called ZIF-8, which consists of a lattice of tetrahedral units made up of a zinc ion attached to four molecules of imidazole, an organic compound. Previous work has shown that ZIF-8 can significantly boost immune responses, but it wasn't known exactly how this particle activates the immune system.

To try to figure that out, the MIT team created an experimental vaccine consisting of the SARS-CoV-2 receptor-binding protein (RBD) embedded within ZIF-8 particles. These particles are between 100 and 200 nanometers in diameter, a size that allows them to get into the body's lymph nodes directly or through immune cells such as macrophages.

Once the particles enter the cells, the MOFs are broken down, releasing the viral proteins. The researchers found that the imidazole components then activate toll-like receptors (TLRs), which help to stimulate the innate immune response.

"This process is analogous to establishing a covert operative team at the molecular level to transport essential elements of the Covid-19 virus to the body's immune system, where they can activate specific immune responses to boost vaccine efficacy," Alsaiari says.

RNA sequencing of cells from the lymph nodes showed that mice vaccinated with ZIF-8 particles carrying the viral protein strongly activated a TLR pathway known as TLR-7, which led to greater production of cytokines and other molecules involved in inflammation.

Mice vaccinated with these particles generated a much stronger response to the viral protein than mice that received the protein on its own.

"Not only are we delivering the protein in a more controlled way through a nanoparticle, but the compositional structure of this particle is also acting as an adjuvant," Jaklenec says. "We were able to achieve very specific responses to the Covid protein, and with a dose-sparing effect compared to using the protein by itself to vaccinate."

Vaccine access

While this study and others have demonstrated ZIF-8's immunogenic ability, more work needs to be done to evaluate the particles' safety and potential to be scaled up for large-scale manufacturing. If ZIF-8 is not developed as a vaccine carrier, the findings from the study should help to guide researchers in developing similar nanoparticles that could be used to deliver subunit vaccines, Jaklenec says.

"Most subunit vaccines usually have two separate components: an antigen and an adjuvant," Jaklenec says. "Designing new vaccines that utilize nanoparticles with specific chemical moieties which not only aid in antigen delivery but can also activate particular immune pathways have the potential to enhance vaccine potency."

One advantage to developing a subunit vaccine for Covid-19 is that such vaccines are usually easier and cheaper to manufacture than mRNA vaccines, which could make it easier to distribute them around the world, the researchers say.

"Subunit vaccines have been around for a long time, and they tend to be cheaper to produce, so that opens up more access to vaccines, especially in times of pandemic," Jaklenec says.

Reference: Alsaiari SK, Nadeef S, Daristotle JL, et al. Zeolitic imidazolate frameworks activate endosomal Toll-like receptors and potentiate immunogenicity of SARS-CoV-2 spike protein trimer. Sci Adv. 2024;10(10):eadj6380. Doi: 10.1126/sciadv.Adj6380

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