The Indian company Bharat Biotech partnered with the National Institute of Virology and the Indian Council of Medical Research to develop an inactivated coronavirus vaccine called Covaxin. India authorized the vaccine for emergency use on Jan. 3, despite a lack of published Phase 3 data showing the vaccine is safe and effective.
A Vaccine Made From Coronaviruses
Covaxin works by teaching the immune system to make antibodies against the SARS-CoV-2 coronavirus. The antibodies attach to viral proteins, such as the so-called spike proteins that stud its surface.
Spike
protein
gene
Spike
protein
gene
CORONAVIRUS
To create Covaxin, Bharat Biotech used a sample of the coronavirus isolated by India’s National Institute of Virology.
Killing the Virus
Once the researchers produced large stocks of the coronaviruses, they doused them with a chemical called beta-propiolactone. The compound disabled the coronaviruses by bonding to their genes. The inactivated coronaviruses could no longer replicate. But their proteins, including spike, remained intact.
Inactivated
genes
Beta-
propiolactone
Beta-
propiolactone
INACTIVATED
CORONAVIRUS
Inactivated
genes
The researchers then drew off the inactivated viruses and mixed them with a tiny amount of an aluminum-based compound called an adjuvant. Adjuvants stimulate the immune system to boost its response to a vaccine.
Inactivated viruses have been used for over a century. Jonas Salk used them to create his polio vaccine in the 1950s, and they’re the bases for vaccines against other diseases including rabies and hepatitis A.
Prompting an Immune Response
Because the coronaviruses in Covaxin are dead, they can be injected into the arm without causing Covid-19. Once inside the body, some of the inactivated viruses are swallowed up by a type of immune cell called an antigen-presenting cell.
Engulfing
the virus
Digesting
proteins
ANTIGEN-
PRESENTING
CELL
Presenting
virus protein
fragments
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Engulfing
the virus
ANTIGEN-
PRESENTING
CELL
Digesting
virus proteins
Presenting
virus protein
fragments
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Engulfing
the virus
ANTIGEN-
PRESENTING
CELL
Digesting
virus proteins
Presenting
virus protein
fragments
HELPER
T CELL
The antigen-presenting cell tears the coronavirus apart and displays some of its fragments on its surface. A so-called helper T cell may detect the fragment. If the fragment fits into one of its surface proteins, the T cell becomes activated and can help recruit other immune cells to respond to the vaccine.
Making Antibodies
Another type of immune cell, called a B cell, may also encounter the inactivated coronavirus. B cells have surface proteins in a huge variety of shapes, and a few might have the right shape to latch onto the coronavirus. When a B cell locks on, it can pull part or all of the virus inside and present coronavirus fragments on its surface.
A helper T cell activated against the coronavirus can latch onto the same fragment. When that happens, the B cell gets activated, too. It proliferates and pours out antibodies that have the same shape as their surface proteins.
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
INACTIVATED
CORONAVIRUS
Activating
the B cell
Matching
surface proteins
SECRETED
ANTIBODIES
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface
proteins
INACTIVATED
CORONAVIRUS
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface
proteins
INACTIVATED
CORONAVIRUS
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface
proteins
INACTIVATED
CORONAVIRUS
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface proteins
INACTIVATED
CORONAVIRUS
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface proteins
INACTIVATED
CORONAVIRUS
ACTIVATED
HELPER
T CELL
Activating
the B cell
Matching
surface proteins
INACTIVATED
CORONAVIRUS
Stopping the Virus
Once vaccinated with Covaxin, the immune system can respond to an infection of live coronaviruses. B cells produce antibodies that stick to the invaders. Antibodies that target the spike protein can prevent the virus from entering cells. Other kinds of antibodies may block the virus by other means.
ANTIBODIES
LIVE
VIRUS
ANTIBODIES
LIVE
VIRUS
ANTIBODIES
LIVE
VIRUS
Remembering the Virus
Covaxin is being tested in two doses, given four weeks apart.
First dose
Second dose
28 days later
First dose
Second dose
28 days later
First dose
Second dose
28 days later
If Bharat Biotech’s Phase 3 clinical trial demonstrates that Covaxin protects people against Covid-19, researchers will have to observe it for months to see how long that protection lasts. It’s possible that the level of antibodies will drop, but the immune system also contains special cells called memory B cells that might retain information about the coronavirus for years or even decades.
Vaccine Timeline
June, 2020 Covaxin is the first coronavirus vaccine created in India to be approved for clinical trials.
July A Phase 1/2 clinical trial begins with 755 participants.
September Results from monkey and hamster studies show that Covaxin provides protection against infection.
Oct. 23 The company announces a Phase 3 trial with up to 25,800 participants.
A dose of Covaxin in Ahmedabad, India.Amit Dave/Reuters
December Covaxin’s Phase 1/2 trial shows the vaccine produces antibodies to the coronavirus without causing serious side effects.
Dec. 22 Bharat Biotech announces a partnership with Pennsylvania-based Ocugen to develop Covaxin for the United States market.
Jan. 3, 2021 The Indian government grants Covaxin emergency authorization, despite no release of Phase 3 data showing the vaccine is safe and effective. The country also authorizes a vaccine made by Oxford University and AstraZeneca.
Sources: National Center for Biotechnology Information; Science; The Lancet; Lynda Coughlan, University of Maryland School of Medicine; Jenna Guthmiller, University of Chicago.
