With the COVID-19 pandemic posing an ever greater global threat, scientists are ramping up efforts to develop a safe and effective vaccine against the coronavirus.

There are many ways to make a vaccine, but the general idea is the same. When the immune system is exposed to a previously unknown pathogen, it usually takes a few days to train and deploy its soldiers against the invasive germ. Vaccines act like a practice drill for the immune system by exposing it to a weak, broken, or fake virus — so that when an actual infection happens, the immune system’s already-trained defenders are ready for the fight.

According to the World Health Organization, over 40 types of COVID-19 vaccines are being developed worldwide. Most fall into one of four categories: attenuated, subunit, recombinant vector, and nucleic acid-based.

Attenuated: Live but Frail

Attenuated vaccines are live viruses that have been weakened in a laboratory. Scientists might grow the virus but not give it enough nutrients, for example. As a result, the virus, despite being viable, is too weak to cause disease. Many common vaccines, including the MMR (measles, mumps, rubella) and smallpox vaccines, are made with this technique. Attenuated vaccines can closely mimic real infections and are thus capable of inducing strong and long-lasting immunity in humans. On the flip side, however, because they involve a live virus, they can potentially pose health risks to people with weaker immune systems.

U.S. biotech company Codagenix is collaborating with the Serum Institute of India to develop an attenuated vaccine against COVID-19, according to the WHO.

Subunit: The Bait

Subunit vaccines involve recipients being inoculated with only the part of the virus that elicits an immune response. This viral component is called an antigen, and it’s what the immune system uses to identify an invader. The immune system has an excellent memory of which antigens it has encountered. So when it detects a potentially harmful virus with a familiar antigen, it knows just how to respond. In the case of the COVID-19 virus, its antigen is a spiky protein on the cell surface.

British pharmaceutical firm GlaxoSmithKline is reportedly collaborating with Clover Biopharmaceuticals, a company based in the southwestern Chinese city of Chengdu, to develop a subunit vaccine based on the aforementioned spiky proteins.

Recombinant Vector: The Sheep in Wolf’s Clothing

Recombinant vector vaccines are made through genetic engineering. Similar to subunit vaccines, recombinant vector vaccines aim to expose the immune system to viral antigens. But instead of injecting the antigens directly, scientists take a snippet of the virus’ genetic code for the antigen and combine it with that of a harmless virus. The engineered virus can then express the antigen needed to generate an immune response without causing an infection.

China’s first experimental vaccine approved for human trials uses this technique, with the team of researchers from the Academy of Military Medical Sciences inoculating their first volunteers last week. The study is aiming to recruit 108 healthy volunteers aged 18 to 60, and to run from March 16 to Dec. 31.

Nucleic Acid-Based: The Instruction Manual

Nucleic acid-based vaccines are the newest vaccine category. They work by injecting parts of the virus’ genetic material, such as DNA or RNA segments, directly into the human body. For these vaccines, scientists tend to favor antigen genes, which are essentially encyclopedias containing all the information needed to recreate antigens once they’re inside human cells.

This technique has only been explored for the last 20 years or so, and thus no DNA or RNA vaccines have yet been approved for human use. But nucleic acid-based vaccines are time savers, as researchers don’t have to grow viral components on a massive scale in the lab. Instead, this process takes place directly within human hosts.

Cutting production time is crucial for vaccine development during a pandemic. For this reason, dozens of pharmaceutical companies are eyeing a nucleic acid-based COVID-19 vaccine.

The first U.S.-developed experimental COVID-19 vaccine given to humans is an RNA vaccine made by the Massachusetts-based biotech company Moderna and the National Institutes of Health. In China, meanwhile, Fudan University is collaborating with Shanghai Jiao Tong University and RNACure Biopharma, a local biotech firm, to develop an RNA vaccine, though human trials are still pending.

Vaccine development is a time-consuming process. Most of the projects that have been announced are still in the early stages, such as testing on animal models. Despite the global effort, only two COVID-19 vaccines have entered early-stage human trials.

Editor: David Paulk.

(Header image: 500px/VCG)