A brief overview of all the Covid-19 vaccines in the pipeline – Quartz

Right now, the best bridge to a new normal is a successful vaccine against Covid-19. Scientists are racing to develop one on an unprecedented timeline, but it could still take a year to 18 monthspossibly longer.

Vaccines are harder to make than ordinary pharmaceuticals. Typical drugs carry out a specific process in the body, and they only have to work only until the kidneys and liver filter them out. Vaccines, though, have to do a bit of biological catfishing: They dupe certain cells in our blood, called B-cells, into responding to a pathogenic threat that doesnt actually exist.

Tricking those cells into producing antibodies against a disease it hasnt yet faced is a difficult process. Scientists need help from benign viruses and bacteria, gene editing tools, and even copies of the infectious pathogen itselfand sometimes combinations of all three. And right now, scientists are throwing all of these strategies at Covid-19 to see what sticks.

At the time of writing, there are 123 vaccine candidates in various stages in the research pipeline. In a best-case scenario, multiple kinds of vaccines would be found safe and effective, so there would be several options for drug manufacturers and distributers to make and ship across the globe. Heres your guide to understanding the different approaches.

The most effective way (pdf) to generate antibodies against an infection is to actually get sick. The next best option? Show your B-cells a copy of the same pathogenbut genetically modified or kneecapped with a chemical like formaldehyde so it cant cause an infection. These vaccines cancause a minor infection if the virus is merely weakened and still capable of replicating, but its not nearly as dangerous as if it were at full-strength.

Scientists have developed inactivated or weakened vaccines for illnesses like measles, chicken pox, and polio. These vaccines are tried and true, but finding a new one requires a delicate balance: It has to be as close to the actual virus as possible, but not capable of replicating like it normally would.

If for some reason, the virus does start replicating, a perfectly healthy person would become sick. This is why safety testing is so critical for these vaccines. Currently, only two vaccine candidates in this category are in early clinical trials: one being developed by the Wuhan Institute of Biological Products, and one by Sinovac Biotech, which is also based in China.

Instead of showing B-cells the entire pathogen, protein subunit vaccines only show the body partsof the virus. For Covid-19, most developers are going after the spike protein that SARS-CoV-2 uses to enter our cells. The hope is that by showing B-cells that characteristic protein, theyll be able to recognize it on the pathogen itself, too. Itd be like showing your B-cells a novelty bedazzled bowling hat, and telling them to watch out for any invader wearing it in the future.

Protein subunits arent able to turn into a full-blown infection. But the immune responses they produce get weaker over time, which means that a person may require boosters throughout their life. Some annual flu vaccines take the form of protein subunits, as does the HPV vaccine. So far, none of the protein subunit vaccines have made it to testing in humans.

Protein subunit vaccines require manufacturers to genetically modify a microbe, like the bacteria E. coli, to produce the desired protein. Then these proteins have to be purified and mixed with adjuvants, which signal to B-cells to pay attention to them. So to speed up the process, scientists have worked out a way to get the body to produce these desired subunit proteins themselves.

Nucleic acid vaccines use either double-stranded DNA (the same genetic material stored in each of our cells nuclei), or messenger RNA (mRNA). These forms of genetic material contain the recipe for the desired proteins, just like our DNA does (mRNA is genetic material that is just a little farther along in the process). Cells within the body translate this foreign genetic material into target proteins, which B-cells then create antibodies against.

The advantage of this approach is that its relatively fast; once scientists have genetically sequenced a novel pathogen, they can isolate target proteins for the body to recreate. The challenge, though, is getting the body to actually respond to them.

Nucleic acid vaccines made with DNA have to get through the cell membrane and the cells nucleic membrane, which protects your DNA.Those with mRNA only have to get through the cell membrane, but theres still an additional hurdle: Even if the cells make the desired protein, they have to fold it into a shape that resembles the actual viral protein. Its like the difference between using a boxed cake mix to make 12 cupcakes versus two round cakes.

A nucleic acid vaccine has never been approved for use. But one of the leading vaccine candidates for Covid-19 uses this approach. Its an mRNA vaccine created by the Cambridge-based company Moderna, and the US government has already invested millions in it, even though its still in early clinical testing.

Another way to get around B-cells failure to respond to subunit vaccines or nucleic acid vaccinesis to try a hybrid approach: using otherweakened or inoculated viruses to transport genetic material that codes for bits of SARS-CoV-2, the coronavirus that causes Covid-19. The carrier virus can make its way into our cells like other infectious diseases wouldbut once it gets there, it produces SARS-CoV-2 proteins that generate the correct antibody response.

Some of these carrier viruses, called viral vectors, are capable of reproducing to a small degree, while others dont at all. Either way, they shouldnt cause an actual illness. The only reason these vaccines would be ineffective is if the recipient already has some form of immunity against the knocked-out vectormaking it impossible for the virus to enter our cells. One virus that scientists like to use is an adenovirus, for example, which often causes the common cold.

The newly-minted Ebola vaccine, which the US Food and Drug Administration approved in December 2019, is a viral vector vaccine. There are two promising vaccine approaches for Covid-19 using this platform, one by researchers at Oxford University, and one from the drug company Johnson and Johnson.

The last main tactic that developers are exploring is another variation of subunit vaccines. Instead of getting B-cells to recognize only certain viral proteins, virus-like particle vaccines introduce all the proteins on the outer shell of SARS-CoV-2. Its like showing B-cells only the menacing trench coat of a potential pathogen. Underneath the trench coat, though, theres nothingno genetic machinery to reproduce and destroy cells.

Currently, there are no virus-like particle vaccines in human trialsbut Medicago Inc., a company based in Quebec City in Canada, is hoping to start theirs in July.

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A brief overview of all the Covid-19 vaccines in the pipeline - Quartz