Inside one lab that’s racing the clock to eradicate the coronavirus pandemic.
So begins this fascinating article discussing a promising approach to vaccinating against not only coronavirus, but potentially any other kind of virus, based on the original first attempt at vaccination against smallpox, pioneered by Edward Jenner in 1896.Louis Falo still has the scar. It’s on the bicep of his left arm, an oblong mark left when a needle scratched into his flesh a tiny bit of toxin—just enough to kickstart an immune response, but not enough to make him sick.
This is how doctors across the United States once vaccinated generations of people against smallpox. The process was so effective that by the early 1950s, scientists declared the deadly viral disease eradicated in North America. Two decades later, America’s doctors stopped administering smallpox vaccines to the general population altogether. Dr. Falo’s scar is the inexpensive price paid to ensure he never got the virus. It would also prove to be an inspiration when he turned his attention toward hopefully eradicating a new deadly virus.
Read the whole article, I'm sure most of you will find it very interesting. Here's another excerpt from the article:
Here's a description of the differences in the Pittsburgh University approach:Just one problem: Making a vaccine is anything but swift. The fastest-ever approved vaccine, for mumps, took four years.
Working tirelessly despite the pandemic-level pressure and the daunting timelines are people like Louis Falo, M.D., Ph.D., an immunologist and skin dermatologist at the University of Pittsburgh. It was there that Dr. Falo and a team of 10 other scientists and physicians began working in January 2020 to discover a vaccine for COVID-19—one they could apply to the skin, like the smallpox vaccine, using only a small patch resembling a bandage.
Here, to me, is the most intriguing difference however:The team at Pitt had previously studied the SARS virus in 2002 and the MERS virus in 2014, two other spike-laden coronaviruses. They figured the S-protein that composes the spikes on the outer envelope of the COVID-19 virus was the most promising antigen target. Within days of the genomic sequence being published, Dr. Gambotto’s team working on computers optimized the published S-protein genetic sequence to efficiently produce pieces of the protein in cultured cells.
Targeting a virus with such precision is a 21st-century invention, the result of computers becoming powerful enough to quickly and cheaply sequence the genetic codes of pathogens. It allows vaccine development to move at lightning speed, which helps explain the 76 different COVID-19 vaccines currently in progress. And although Dr. Falo’s team has worked quickly, their vaccine is not the first to enter a clinical trial.
Starting on March 16, a potential vaccine was injected into 45 healthy adults in Seattle and Atlanta. The concoction was brewed by Moderna, a biotechnology firm based in Cambridge, Massachusetts, and developed in tandem with scientists from the National Institute of Allergy and Infectious Diseases. (Its director, Anthony Fauci, M.D., is America’s pandemic guru.) Moderna’s vaccine is an example of mRNA technology: It encodes a mutated spike protein by shooting a snippet of genetic RNA into the body. In other words, the vaccine provides instructions to the body’s cells so they can produce an antigen internally.
“We’re just using one protein that is important for inducing an immune response: the spike protein. We essentially are optimizing the immune response to that target protein,” says Kizzmekia Corbett, Ph.D., lead scientist for coronavirus vaccine research at NIAID. “Our hypothesis is that with this vaccine strategy, we’ll get better antibodies.”
Typically vaccines are delivered via needle directly into the muscle, but the skin also generates a potent immune response—and contains more immune cells than muscle tissue. The human dermis is awash with dendritic cells that act like scouts, moving around the skin and searching for foreign pathogens. When they discover one, they break off a piece of it, then move quickly into the body’s lymphatic system, traveling in earnest to present the invader to B and T cells, which generate the antibody response. Dr. Falo’s thought was simple: Forget injecting the antigen into the blood stream. Stick it into the skin instead, and let the dendritic cells do all the heavy lifting.
“The skin is your first line of defense, constantly getting bombarded with bacteria and viruses,” he says. “Our goal was to take what we learned from smallpox and develop technology that was able to reproduce that, but in a much more controlled, efficient fashion.”
Having a doctor etch viral antigen into a person’s skin is cumbersome, not to mention a lousy way to combat a pandemic. While he wasn’t expecting a new coronavirus to shut down the world, Dr. Falo was nonetheless searching for an easier way to deliver skin inoculations. For the last nine years, he and fellow Pitt researchers have been developing what he calls a microneedle array: a small patch that resembles a Band-Aid covered in 400 microscopic needles, and something that a person could theoretically create at their local makerspace. The molds for these arrays can be designed in computer software, then manufactured by a high-resolution 3D laser printer down to the nanometer.
Meanwhile, the needles themselves are made from sugar substances capable of dissolving into the skin. With S-proteins produced and microneedle-array molds printed, Dr. Falo and his fellow scientists put the final touches on their vaccine. The bits of viral protein were mixed in with a sugary solution, which was poured into the molds. Two sessions in the centrifuge first pulled the antigen down into the needles before hardening them. Afterward, team members used tweezers to pull the microneedle arrays from the molds, almost like breaking ice out of its tray. Left over was a square patch, filled with COVID-19 vaccine, that could be comfortably applied to a person’s arm, and removed in under 15 minutes.