Covid-19 spike protein as vaccine?

Question

The genome of Covid-19 was mapped in early Feb. The gene for a protein spike was used to produce these spike proteins. 3-D microscopy of this synthesized spike has been produced. Quoting McLellan from this article:

"the molecule looks really good; it's really well behaved; the structure kind of demonstrates that the molecule is stable in the correct confirmation that we were hoping for," McLellan said. "So now we and others will use the molecule that we created as a basis for vaccine antigen."

Also saying:

In theory, the spike protein itself "could be either the vaccine or variants of a vaccine," McLellan said. When you inject this spike-protein-based vaccine, "humans would make antibodies against the spike, and then if they were ever exposed to the live virus,"

The article goes on to say:

Their colleagues at the NIH will now inject these spike proteins into animals to see how well the proteins trigger antibody production. Still, McLellan thinks a vaccine is likely about 18 to 24 months away. That's "still quite fast compared to normal vaccine development, which might take like 10 years," he said.

My question is: Why not inject, or drink, these spike proteins for immunity to Covid-19? Why expect an 18-24 month wait? The anti-body production response should occur(and be detectable) in days?

Answer 1

Vaccines need extensive testing before they can be used. There's essentially no medical intervention which requires more testing than vaccines, which are used in extremely large numbers of healthy patients.

Generally this involves basic research, animal testing, Phase I testing ("Is it safe in humans? At what dose?"), Phase II testing ("Is it effective? At what dose? Are there side effects?"), and Phase III testing ("Is it safe and effective across all different subpopulations?").

As just one example of what could potentially go wrong: many/most COVID-19 deaths involve cytokine storms which are, roughly, damaging inflammatory immune overreactions. Priming the immune system could potentially worsen them and increase deaths by strengthening the immune response. (It doesn't seem likely, but this is why we test.)

Answer 2

We don't know if the spike proteins are an immune epitope that can be recognized by the human immune system.

a team of researchers at La Jolla Institute for Immunology, in collaboration with researchers at the J. Craig Venter Institute, provides the first analysis of potential targets for effective immune responses against the novel coronavirus. The researchers used existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system. ..

When the immune system encounters a bacterium or a virus, it zeroes in on tiny molecular features, so called epitopes, which allow cells of the immune system to distinguish between closely related foreign invaders and focus their attack. Having a complete map of viral epitopes and their immunogenicity is critical to researchers attempting to design new or improved vaccines to protect against COVID-19, the disease caused by SARS-CoV-2.

"Right now, we have limited information about which pieces of the virus elicit a solid human response," says the study's lead author Alessandro Sette, Dr. Biol.Sci, a professor in the Center for Infectious Disease and Vaccine Research at LJI. "Knowing the immunogenicity of certain viral regions, or in other words, which parts of the virus the immune system reacts to and how strongly, is of immediate relevance for the design of promising vaccine candidates and their evaluation."

While scientists currently know very little about how the human immune system responds to SARS-CoV-2, the immune response to other coronaviruses has been studied and a significant amount of epitope data is available.

https://marlin-prod.literatumonline.com/pb-assets/journals/research/cell-host-microbe/PDFs/CHOM_2264_S50.pdf

There's also experimental data to suggest that strong binding of the spike proteins to the ACE2 receptor, that could cause ARDS as it blocks inhibition of AT1-R.

Answer 3

From this paper it appears that theses spikes might be used in this way.

MNA delivery of either rSARS-CoV-2-S1 or rSARS-CoV-2-S1fRS09 induced substantial and statistically significant increases in antigen-specific antibodies responses as soon as week 2 compared to pre-immunization and week 1 responses.

The significant antibody titers we observed at the early time points before boosting strongly supports the feasibility of our MNA-SARS-CoV-2 vaccines,

Neutralization assays are important to ensure antibody function; however, at this early timepoint, we do not have access to validated assays for neutralizing antibodies against SARS-CoV-2.

Taken together, our studies demonstrate the speed at which vaccines against emerging infections can be designed and produced using the recent advances in recombinant DNA technology. Combining emerging biotechnology methods with bioengineering advances in vaccine delivery strategies, it may now be possible to rapidly produce clinically-translatable vaccines against novel pathogens for human testing and subsequent global distribution in time to significantly impact the spread of disease.

They discuss the benefits of using microneedle arrays(MNAs) to deliver a potential vaccine through the skin. A production strategy and timeline to create a vaccine is included.