From Phase 0 to long-term study, a look at how long it actually takes to develop a vaccine

The Modi govt has asked ICMR to fast-track the trial for Covaxin, a Covid vaccine, and hopes to roll it out in six weeks, in time for Independence Day.

A scientist working at a lab at CCMB in Hyderabad (representational image) | Suraj Singh Bisht | ThePrint

Bengaluru: Any news of vaccines is an immediate head-turner given that economies have crashed and countries have come to a standstill while the Covid-19 pandemic continues to rage. Currently, more than 1 crore people have been infected worldwide in the six months since the first case was reported in China’s Wuhan. The disease has no known treatment yet.

The Narendra Modi government more than turned heads Friday with reports that it was hoping to have a vaccine ready in six weeks, the trial for which is yet to begin.

Vaccines are complicated to develop and usually take long periods of time to monitor for efficacy, safety and side effects.

Additionally, it is unethical to expose participants in a trial directly to a pathogen, thus prolonging the duration of observation. But due to the extreme urgent need for a Covid vaccine, many vaccine trials have taken the controversial decision to purposely infect study participants to arrive at results faster.

ThePrint looks at how long vaccines take to develop, how they are expedited, and what the different types of vaccines being developed for Covid are.

How vaccines work

Vaccines are a biological substances which, when injected into our bodies, kickstarts our immune response to produce antibodies. They do so by carrying a weaker form of a bacteria or virus or any disease-causing pathogen.

The dosage of the pathogens doesn’t hurt our body but is recognisable enough as a foreign invader so that the immune system starts fighting it. Our immune system now remembers the pathogen it fought off, thus recognising it whenever it or a similar pathogen enters the body the next time. This results in a vaccinated person’s immune system responding faster, ensuring the person doesn’t get the disease.

Vaccines can be both prophylactic to prevent a disease, and therapeutic to boost a natural immune response to a disease that has already infected the body, like cancer.

Vaccines, in general, protect the population and have been used to control epidemics as well as eradicate diseases. The world has eradicated two so far — small pox in humans and rinderpest in animals.

Stages of vaccine development

Vaccines and drugs go through multiple stages of development, and with each stage, multiple vaccine candidates get filtered out.

An exploratory stage of two to four years is when the process typically begins, where antigens are identified and a potential roadmap for the vaccine is drawn out. They then enter a pre-clinical stage or Phase 0 where microbial material is tested in vitro (in cell and tissue cultures) as well as on animals to understand results that could be expected in humans. This stage typically lasts one to two years.

In the face of a pandemic like Covid, researchers are ethically in the clear to skip these phases and directly launch into Phase I. This is when the vaccine is introduced to humans first. The objective is to establish the safety of the vaccine and understand the extent of immune response. It typically involves less than 100 people, and could last between several months to a year or two.

If safety is established, Phase II commences where 100 to 300 people are enrolled to test efficacy and understand side effects. This lasts for about two to three years.

Often, to expedite testing, Phases I and II are combined.

Phase III trials are the most crucial. They last for about five to 10 years, and enrol around 3,000 participants for one vaccine. The successful conclusion of Phase III is when actual efficacy can be established.

Once statistically-significant efficacy is proven, a vaccine undergoes an approval process (typically two years), which also involves manufacturing, scaling up, and drawing a vaccination drive plan, after which it is rolled out or distributed. Once vaccination drives are underway, Phase IV commences, where long-term safety and efficacy is studied.

The average time of vaccine development is anywhere from 10 to 15 years in non-emergency situations.

Different kinds of vaccines

Vaccine categories are broadly classified into two.

Live, attenuated vaccines carry an extremely weakened pathogen which can’t cause the disease, such as the measles or BCG (Bacillus Calmette–Guérin) vaccines. Killed or inactive vaccines use either dead pathogens or parts of a pathogen. These vaccines are not as powerful as live ones and typically require booster shots.

A killed vaccine can either carry the entire killed pathogen, such as the rabies or influenza vaccines, or be a sub-unit vaccine which doesn’t contain a full cell but instead contains parts of a pathogen such as sugars or proteins found on the surface of a bacteria or virus. Hepatitis B and Human papillomavirus (HPV) vaccines are sub-unit vaccines. Even some developmental Covid vaccines, like Novovax use the spike protein of the virus to help antibodies recognise the protein later.

There are now different kinds of genetic vaccines using newer technologies, such as DNA/RNA vaccines where the genetic material of a pathogen is introduced to our bodies. A number of RNA vaccines are currently being tested for Covid.

There are also viral vector vaccines, where one virus carries genetic material of another into our bodies directly, such as the Oxford vaccine being developed for Covid, where the spike protein gene is inserted into a chimp adenovirus.

The global projected timeline for a functioning Covid vaccine to be developed is at least nine to 12 months, with vaccine manufacturers and other experts saying that it could take up to two years.

No vaccine has been developed successfully within timelines similar to Covid.

The fastest to be approved and licensed was the mumps vaccine, which went from collecting viral samples to being licensed in four years. The Ebola vaccine was also fast-tracked as a global response to the severe 2014 outbreak, even though the disease had been around since the 1970s. After testing and development, the vaccine was approved and licensed between November and December of 2019, and is expected to roll out this year.