SARS-CoV-2, the virus causing the COVID-19 pandemic, has pushed several pharmaceutical companies into action. Globally, there are 23 vaccine cadidates undergoing human trials as on July 15. Of these, two, namely China’s Sinovac and University of Oxford-AstraZeneca, have just entered the final leg initiating phase 3 trials.
Phase 3 trials could take at least 12 months, which means the earliest a Covid-19 vaccine can hit pharmacies is July, 2021. As per the US FDA guidelines effective June 30, successful candidates must provide data from placebo-controlled trials indicating their vaccine is at least 50 per cent effective in order to be authorised for use.
India’s Bharat Biotech and Cadila Healthcare Ltd are just beginning phase 1/2 trials. Besides, there are 140 other vaccine candidates, including those by Indian companies like Sun Pharmaceuticals, Aurobindo Pharmaceuticals, Biocon and Indian Immunologicals Ltd, which are undergoing preclinical testing.
The pre-clinical stage includes vaccine testing in laboratories (in vitro tests) and studies conducted in animals (in vivo tests) to evaluate the potential of the vaccine. The next stage includes clinical trials done on humans in three phases. Phase I is done on less than 100 healthy volunteers followed by phase II on several hundred volunteers. Phase III is done on a much larger scale involving up to several thousand people.
Bharat Biotech
The Hyderabad-based vaccine maker is the first Indian company to enter clinical trials for its indigenously developed vaccine candidate. As per data furnished with the CTRI, the company has begun a seamless Phase 1 trial which will be followed by a randomised, double-blind, multi-centre Phase 2 study to evaluate the safety, reactogenicity, tolerability and immunogenicity of the whole-virion inactivated Sars-Cov-2 vaccine (BBV152) named Covaxin, in healthy volunteers.
These clinical trials are being conducted across 12 cities including AIMS, Patna and New Delhi, in Nagpur, Jajapur, Belgaum, Visakhapatnam, Hyderabad, and others. The Phase 1 trial includes 375 volunteers aged between 18 and 55, while Phase 2 will take 750 volunteers aged 12 to 65. Three groups of healthy volunteers will receive two intramuscular doses of BBV152 vaccine formulations. The esimated duration of the trial is three months, ie., it is expected to end in October.
Live attenuated virus
Vaccines introduce antigens, which are simply foreign proteins into patients. When one gets infected with the virus, the foreign protein recognises the virus, protects the patient from developing the disease and destroys the virus. One such treatment includes infecting people with a live but weakened (“attenuated”) virus that can make copies of itself and activate a strong immune response without making people sick.
Inactivated virus
Here the disease-causing virus has been killed with heat or chemicals, so it won’t make you sick. This is used in patients who are averse to live attenuated virus vaccine. Inactivated virus vaccines are considered safer, but aren’t deemed as strong as live attenuated virus vaccines, so additional doses are given to strengthen the immune response.
Protein Subunit
These are similar to inactivated virus vaccines. Only, they don’t contain live viruses. Instead, protein fragments of a destroyed virus are introduced into the vaccinated person to trigger an immune response in their body to take on the virus.
Virus-like particles
Here too, vaccines don’t contain live viruses, but resemble the virus just enough to mimic the outer shell of the virus to trigger an immune response without causing disease
Nucleic-acid or gene-based
This approach uses genetic engineering to deliver nucleic acids (DNA or RNA) that carry instructions to produce viral proteins rather than delivering the proteins themselves into human cells to trigger the immune response. Because they consist only of nucleic acids (DNA or RNA) and no other viral parts, they are safer, easier and quicker to make. DNA-based vaccines inject a genetically engineered blueprint of viral gene(s) into small DNA molecules called plasmids, which instruct cells to build
viral proteins. RNA-based vaccines work similarly, but instead of using plasmids to get into cells, they use fatty molecules called lipids, which then instruct cells to build viral proteins to trigger an immune response.
Viral vector
Unlike DNA or RNA-based vaccines that use plasmids or lipids, viral vector vaccines use weakened viruses called vectors to transport the blueprint of viral genes. Replicating viral vector vaccine uses a live but weakened vector that replicates within cells and produces viral proteins and strengthen the immune response. Non-replicating viral vector vaccine uses a killed viral vector, but doesn’t deliver long-lasting immunity. Therefore, booster shots may be needed to provide ongoing protection against the virus
Antibodies
The immune system comprises antibodies, which are part of our natural defence systems, to detect bacteria or viruses and target them for destruction. Some of the treatments include convalescent plasma, where scientists either use antibodies from blood from recovered patients
Antivirals
Typically, viruses carry only nucleic acid — DNA or RNA — with a protective shell around them. But it multiplies only when attached to animal or human cells. Antivirals stop viruses from making more copies of themselves by blocking one or more steps in the replication process
Cell-Based Therapies
Cell-based therapies transfer live cells into patients to treat the disease. How are they made? Scientists take cells either from patients or donors and transfer them with or without alteration. Cell sources include those from fat tissue or bone marrow, from placenta and others
Devices
Then there are devices such as those for blood purification to treat the disease. The machines filter patients’ blood to remove excess proteins or toxins that are causing problems, else they could eventually lead to respiratory or organ failure in coronavirus patients
RNA-Based Treatments
In this type of Covid-19 treatments, molecules act as messengers, literally. Their sole job is to carry either of the two instructions to human cells: build useful proteins that can strengthen immune system or block harmful proteins collapsing the immune system
Others
Potential treatment lines being explored/under use include steroids, malarial drugs, drugs treating high blood pressure, drugs treating over-reaction of the immune system (known as a cytokine storm), drugs treating autoimmune diseases, and drugs preventing blood clots
Text: Sunitha Natti
Source: WHO, CTRI, Milken Institute