As scientists around the globe race to produce coronavirus treatments, a team at the University of Pittsburgh claimed Thursday that it may have taken a significant step toward a SARS-CoV-2 vaccine, the= virus that causes Covid-19.
Their work, which is done in mice, is detailed in the first, peer-reviewed scientific study to propose a scalable vaccine for the virus.
These preliminary-and-promising findings were published Thursday in the journal eBiomedicine.
In mice, the vaccine appears to enable the production of immune antibodies that effectively fight off the SARS-Cov-2 virus. These antibodies began to emerge as early as two weeks after immunization, the scientists report.
The pre-clinical research is the first coronavirus vaccine study to undergo peer-review by other scientists, a major milestone in the race to develop a vaccine.
"This is the first coronavirus vaccine candidate to achieve this milestone," Donald Yealy, chair of the University of Pittsburgh's School of Medicine, said Thursday during a press conference.
Different approaches — The Pittsburgh team is joined in the chase for a vaccine by different research teams, and the U.S. government has accelerated clinical trials for two other vaccine candidates that show similar promise. Already, people throughout the world are volunteering as guinea pigs for these vaccine candidates.
There are some key differences in how each of the top vaccine candidates work, and how they would be delivered to human subjects.
The vaccine candidate tested in this research is a recombinant protein subunit vaccine. Essentially, the vaccine is designed to mimic a protein on the surface of the coronavirus called a spike protein. The team has worked in the past on similar vaccine designs to target other coronaviruses, like MERS and SARS.
If you look at a picture of a coronavirus, you'll notice characteristic spikes — these spike proteins are "an important target for vaccine development," the researchers say. The spikes are like keys the virus uses to unlock your cells. That lock is a protein called ACE2, which is commonly found on the surface of cells in the respiratory and digestive systems.
This vaccine design is quite different to that used in other common vaccines. It is not made of a dead or weakened virus (like the measles vaccine is). It is also not the same as a messenger RNA (mRNA)-based vaccine of the kind now entering Phase-1 clinical trials, which essentially directs a person's cells to produce an optimal spike protein to prevent the virus from entering into cells.
"Our vaccine does not rely on the body to make the protein, like many experimental vaccines under development. Because we are not using the old virus, our approach is also relatively safe," Andrea Gambotto, the study's other senior co-author, said.
Design matters — The vaccine is also unusual in that it is designed to be delivered using a micro-needle array, a band-aid-like patch of 400 dissolvable needles that sits on the skin — a technique the team suggests could increase its efficacy.
The array plays an important role in encouraging a robust immune response, said Louis Falo, a researcher at the University of Pittsburgh and a senior co-author on the study.
"The skin is our first line of defense against viruses, bacteria and other harmful invaders. Because of that it has evolved to be very efficient at mounting immune responses, which means less vaccine is needed compared to a traditional shot."
The team tested the microarray design against a traditional single injection shot, and found the microarray delivery resulted in a more robust immune response.
In a release accompanying the research, described the microarray patch as feeling "kind of like Velcro" on the skin — quite different from the shot delivery we are perhaps more familiar with.
At the same time, the micro-needle array design means the vaccine is shelf stable, which means it doesn't need to be refrigerated or stored in special ways, unlike other vaccines like the flu shot. It is also a highly scalable design: One person in the lab can make "hundreds" of the micro-needle arrays, Falo said.
Early days — This vaccine has been designed to be as scalable as possible.
In the paper, the team writes that they have developed standard operating procedures that would allow the "rapid development of clinic grade" SARS-Cov-2 vaccines.
But big questions remain as to whether or not it actually works the way it should.
To be clear, this is a very early trial of this vaccine. From here, it will need to go through safety and dosage testing in humans, or what is known as a phase-1 clinical trial. After that, scientists will be able to move on to testing the vaccine in a phase-2 clinical trial, which is a test of how effective the drug is in people with the disease, and whether it has any short-term side effects.
Usually, such careful vaccine development takes years. But scientists across the world are racing to get through these stages within months.
The most-rapid timeline for any vaccine to come to market is probably a year from now, scientists speculate. But a more detailed timeline isn't clear yet, the researchers behind this candidate say. But they will be ready for when the time comes.
"What I can tell you, is that once we have been given approval we will be ready to go with the vaccine," said Falo.
Methods: We first generated codon optimized MERS-S1 subunit vaccines fused with a foldon trimerization domain to mimic the native viral structure. In variant constructs, we engineered immune stimulants (RS09 or flagellin, as TLR4 or TLR5 agonists, respectively) into this trimeric design. We comprehensively tested the pre-clinical immunogenicity of MERS-CoV vaccines in mice when delivered subcutaneously by traditional needle injection, or intracutaneously by dissolving microneedle arrays (MNAs) by evaluating virus specific IgG antibodies in the serum of vaccinated mice by ELISA and using virus neutralization assays. Driven by the urgent need for COVID-19 vaccines, we utilized this strategy to rapidly develop MNA SARS-CoV-2 subunit vaccines and tested their pre-clinical immunogenicity in vivo by exploiting our substantial experience with MNA MERS-CoV vaccines.
Findings: Here we describe the development of MNA delivered MERS-CoV vaccines and their pre-clinical immunogenicity. Specifically, MNA delivered MERS-S1 subunit vaccines elicited strong and long-lasting antigen-specific antibody responses. Building on our ongoing efforts to develop MERS-CoV vaccines, promising immunogenicity of MNA-delivered MERS-CoV vaccines, and our experience with MNA fabrication and delivery, including clinical trials, we rapidly designed and produced clinically-translatable MNA SARS-CoV-2 subunit vaccines within 4 weeks of the identification of the SARS-CoV-2 S1 sequence. Most importantly, these MNA delivered SARS-CoV-2 S1 subunit vac- cines elicited potent antigen-specific antibody responses that were evident beginning 2 weeks after immunization.
Interpretation: MNA delivery of coronaviruses-S1 subunit vaccines is a promising immunization strategy against coronavirus infection. Progressive scientific and technological efforts enable quicker responses to emerging pandemics. Our ongoing efforts to develop MNA-MERS-S1 subunit vaccines enabled us to rapidly design and produce MNA SARS-CoV-2 subunit vaccines capable of inducing potent virus-specific antibody responses. Collectively, our results support the clinical development of MNA delivered recombinant protein subunit vaccines against SARS, MERS, COVID-19, and other emerging infectious diseases.