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Baltimore Sun: Bank of antibodies against nasty viruses that’s proposed for MD to prevent pandemic

Read the full article in the Baltimore Sun or in Yahoo!News.

By: Meredith Cohn, Baltimore Sun

Monday, November 29th, 2021

As the world continues to grapple with the coronavirus pandemic that has claimed more than 5 million lives, a group of researchers is working to get ahead of the next killer pathogen.

They aim to identify and establish a bank of warrior antibodies in Maryland, close to the National Institutes of Health in Bethesda. The antibodies would be derived from a who’s who of viruses most likely to wreak havoc, such as coronaviruses, influenzas, and flaviviruses that cause Zika and debilitating conditions such as encephalitis.

These are the same types of lab-made monoclonal antibodies derived from survivors’ blood that are being used to treat early cases of COVID-19 and prevent new ones.

“The idea is we use this stuff to manage any early pandemic, to prevent it from getting out of control,” said Dr. James Crowe, a longtime infectious disease expert who founded the initiative, called Ahead100, and is director of the Vanderbilt Vaccine Center in Nashville, Tennessee.

“We know we can make these fast,” he said. “But what’s fast? That led to the idea of making them ahead of time so we had them on Day Zero.”

The bank is one of many efforts that could better equip the world for what comes next. Other proposals center on enhanced surveillance and diagnostic tools, and new therapies such as antivirals and vaccines, as well as beefing up manufacturing capabilities, employing more public health workers and expanding supply stockpiles, according to plans outlined recently by the administration of Democratic President Joe Biden.

Ahead100 is expected to cost $2.5 billion to make antibodies for 100 pandemic candidate viruses and get them through initial safety trials. This will set up production by biotech companies that normally don’t make such investments without a ready market, like during an outbreak.

The initiative was launched by a nonprofit group called the Global Pandemic Prevention & Biodefense Center, which in turn was initiated by a regional nonprofit public-private partnership created in 2019 in the Washington metro area called Connected DMV (for District of Columbia, Maryland and Virginia).

The antibody bank is set to open in 2022 in Montgomery County, and is seeking government, private and philanthropic investment, as well as support from research universities and the biotech industry. The state of Maryland provided $300,000 for a feasibility study, and staff of the state Department of Commerce are serving on the steering committee for the biodefense center.

Crowe acknowledged that fundraising could be a challenge with so many pandemic priorities. But he points to the effectiveness of the monoclonal antibodies already in use for COVID-19 and past outbreaks.

People were slow to use monoclonal antibodies during the pandemic, largely because they didn’t know about them and no one recommended them. Use grew after states’ health officials began promoting their stocks and doctors learned of their effectiveness. Studies showed they reduced the risk of hospitalization by 70% in vulnerable people who were not vaccinated and caught the virus. The Biden administration bought and shipped about 100,000 doses of the antibodies a week to states during the summer and upped the doses by 50% in September.

In Maryland, dozens of facilities are offering monoclonal antibody infusions. Nearly 20,400 doses were used by mid-November, according to the Maryland Department of Health, which has marketed the therapy to older adults and those with underlying health conditions.

“We estimate that we have avoided 956 hospitalizations and 391 deaths thanks to these lifesaving treatments,” said Andy Owen, a health department spokesman, adding there is “ample” inventory.

The antibodies work by recognizing the invading virus, binding to it and preventing it from entering cells in the body where they replicate and spread. The infusions are done at special centers with a doctor’s prescription, or, in Maryland, if people self-attest their need.

Crowe said researchers are working to develop antibodies that can be administered more easily through intramuscular injections. His lab at Vanderbilt has licensed an injectable version to AstraZeneca that awaits federal authorization.

Antibody infusions used now are made by Eli Lilly and Co. and Regeneron Pharmaceuticals Inc..

Such antibodies work in a similar way to vaccines, but aren’t typically as long-lasting, a month or two rather than a year or more. Crowe’s researchers hope to extend the life span of such antibodies to provide a longer bridge of around a year, giving more time to develop vaccines.

While antibodies’ uses are proven, developing and stockpiling antibodies will have challenges beyond costs. How do researchers identify the precise viruses, how do they produce and distribute the antibodies quickly to those who need them most and what if the viruses they work on mutate?

“Monoclonals are an excellent therapy, and some of the biggest barriers to their use have been expense and challenges with administration,” said Gigi Gronvall, a virologist and senior scholar in the Johns Hopkins Center for Health Security who is not involved with the bank.

“In principle, they provide a great deal of protection and can give people — especially immunocompromised people who are unable to mount a good response to a vaccine — instant immunity,” she said. “It is still a good idea, though the devil will be in the details for this particular venture.”

Crowe said research conducted during the process should help reduce development and manufacturing costs, speed of production and inform how to retool quickly. The initiative also is considering distribution methods to ensure equity, an issue that has plagued the COVID-19 vaccine rollout during the pandemic.

Dr. Arturo Casadevall, chair of the department of molecular microbiology and immunology in the Johns Hopkins Bloomberg School of Public Health, agreed that monoclonal antibodies work well.

But he said they have to hit their mark. Even now, scientists monitor the coronavirus monoclonal antibodies to ensure that they are effective against new strains, with some versions discontinued.

Still, he praised Crowe’s work and said if the banked antibodies only get close, they still will save development time. And he said preparation is critical considering the pace of outbreaks in the past two decades: SARS, MERS, Ebola, influenza, Zika.

“They’re happening about every three, four years and, from that point of view, preparedness makes sense, having stuff we can deploy right away,” Casadevall said.

“The problem arises in deciding what you are going to do,” he said. “This coronavirus wouldn’t have been in the bank. There are many nasty viruses out there. At least you’d have a head start.”

Casadevall has researched and championed convalescent plasma, which deploys antibodies taken directly and cheaply from survivor’s blood without need for a lab. It matches circulating strains, but trials during the coronavirus pandemic have been mixed. However, Casadevall said the most recent reviews show promise and he and others are urging doctors to treat patients with it.

Crowe also was an early supporter of plasma, but found it didn’t always help because it often lacked high enough levels of antibodies. With monoclonal antibodies, a sophisticated system sifts out the strongest antibody cells to put in the recipe every time.

He understands the proposed antibody bank faces hurdles, and that begins with identifying his pandemic 100 — the viruses to bank antibodies against.

“Will the next one be a Nipah virus or a Lassa virus?” he said. “We don’t believe experts can predict, but we think we can make a list that includes the next one if the list is large enough. We have the technology and know what to do. It’s just a matter of, ‘Will we have the resources?’”


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