The story so far: A Phase-1 clinical trial on 45 healthy volunteers between the ages of 18 and 55 years has begun in Seattle, U.S., about 100 days after the whole genome sequence of the novel coronavirus (SARS-CoV-2) was shared by Chinese researchers. Different vaccine approaches are being undertaken against the novel coronavirus (SARS-CoV-2) even as 11,402 people have succumbed to the pandemic worldwide so far (March 21, 3.40 p.m.). The vaccine that is being tested in the U.S. is called mRNA (or messenger ribonucleic acid)-1273 and developed in partnership with the Vaccine Research Center at the National Institutes of Health (NIH) and their collaborators at the biotechnology company Moderna, Inc. based in Cambridge, Massachusetts, U.S.
What are vaccines? How are these made?
Vaccines are one of the most effective tools to prevent diseases. A vaccine is a substance that resembles the disease-causing agent (also called pathogen) but does not cause the disease. It trains the body’s immune system to recognise and kill the pathogen, and creates a memory for the future. Vaccines are available to protect us against many life-threatening diseases such as polio, influenza, meningitis, typhoid, tetanus, diphtheria, and certain types of cancers. Vaccines have also been responsible for eradication (or near eradication) of deadly diseases such as smallpox and polio.
There are multiple ways to make vaccines. For a killed vaccine, the pathogen can be grown outside the body, purified and inactivated with chemicals. An example of this is the injectable polio vaccine. Alternatively, the pathogen can be weakened by repeated culture or by genetic means. An example of this would be the oral polio vaccine — the kind used in the ‘Pulse Polio Programme’. One of the proteins on the pathogen surface can also be produced artificially and used to raise immunity. An example of this would be the Hepatitis B vaccine.
What vaccines are being developed against COVID-19?
According to the World Health Organization, over 40 different candidate vaccines for COVID-19 are in development. These include an inactivated vaccine being developed in China (Sinovac) using purified COVID-19 virus killed with formaldehyde (a chemical). A live attenuated vaccine being developed by Codagenix, a U.S.-based company in partnership with the Serum Institute of India (Pune), uses a genetically engineered COVID-19 virus that replicates very poorly. There are multiple other vaccine candidates under development that use DNA, RNA, viral vector and subunit protein platforms.
One vaccine against COVID-19 is already in trials. What is it about?
An experimental COVID-19 vaccine called mRNA-1273 was developed by Moderna, a biotechnology company based in Cambridge, Massachusetts in the U.S. in partnership with the Vaccine Research Center at the National Institutes of Health (NIH), U.S. A Phase 1 study to evaluate its safety and immunogenicity (i.e. ability to raise immune responses) in humans is being conducted by the NIH.
The novel coronavirus causing pneumonia in Wuhan, China was identified on January 7; China shared its genetic sequence on January 12. On February 24, the mRNA-1273 vaccine was sent to NIH for human testing and on March 16, it was given to the first set of human volunteers. Never before has a candidate vaccine been developed so quickly — from sequence to product in 42 days and start of testing in 63 days.
What is the mRNA vaccine?
The genetic blueprint (or code) in living organisms is stored in a double-stranded molecule called DNA (deoxyribonucleic acid), which makes proteins that are responsible for nearly every function in the human body. The conversion of DNA code into proteins requires a single-stranded molecule called the mRNA (messenger ribonucleic acid). In an analogy with computers, one may think of the DNA as the hardware, the mRNA as the software and proteins as the applications.
The mRNA-1273 is a piece of RNA that carries the code to make the COVID-19 virus Spike protein when introduced into cells. This protein present on the virus surface is critical for its entry into cells. Immunity (antibodies) to the Spike protein can block virus entry and its multiplication, and thus ameliorate the disease.
While simple to engineer, mRNA can degrade easily. Therefore, it has to be protected with a coating that can also target it to the cells of choice when injected into the body.
How long does it take to develop a vaccine?
It can take years to develop vaccines — first in laboratories to show proof-of-concept, then developing a manufacturing process to make stable and a highly pure product to be tested in animals and humans, and finally for the market.
The COVID-19 vaccine has been fast-tracked into humans without prior testing in animals. Still, it may take one to two years for the clinical trials to be over. Since there is no guarantee that the mRNA-1273 (or another) vaccine would work, a rich pipeline of over 40 candidates is important.
How much does it cost to develop it? Who funds it?
It takes millions of dollars to develop and test a vaccine. Either for-profit companies or philanthropic foundations and countries cover the costs.
The mRNA-1273 vaccine is supported by the Coalition for Epidemic Preparedness Innovations (CEPI), a not-for-profit grouping of foundations and countries. India is a member of CEPI. Besides mRNA-1273, CEPI has funded the development of at least five other COVID-19 vaccines, with an overall commitment of $23.7 million.
Is a virus needed to develop a vaccine against it?
With modern molecular tools and technologies, isolating a virus is not required to make a vaccine against it. The genetic sequence can be obtained directly from infected patients and this can be converted into proteins using various platform technologies.
This makes it possible to have vaccines ready for hundreds of pathogens that have not yet infected humans, but have the potential to do so in future.
Shahid Jameel is CEO, Wellcome Trust/DBT India Alliance, Hyderabad and New Delhi