The world is in a race against time to figure out an effective vaccine for the novel coronavirus. And while Russia has already brought one into use – albeit not without controversy – most countries are looking at having a vaccine ready by early next year. Though it seems like we have been reeling under the pandemic for a long time, 18 months is practically no time to develop a vaccine.
Developing a vaccine can – and has – taken decades. That’s because the attrition is high, and multiple candidates and studies are needed to produce a licensed vaccine. Even the vaccine that is considered to be the fastest developed – for mumps – took four years and was licensed in 1967. It took another decade for it to be recommended for routine use in the United States.
The measles vaccine, for instance, was almost a decade in the making, though the disease has been around since the 17th century. It was in 1954 that Dr Thomas Peebles and John F Enders collected samples to isolate the measles virus, in which they succeeded. But it was only in 1963 that Enders and his colleagues were able to transform the isolated virus into a licensed vaccine. And it was another five years before an even weaker measles vaccine began to be distributed. It was developed by Maurice Hilleman.
Rotavirus, which is the most common cause of severe diarrhoea in children and infants, had its first vaccine in 1998. However, it was withdrawn in 1999 due to safety related concerns. It was found to be responsible for a condition called intussusception. After that, a rotavirus vaccine wasn’t formulated until 2006.
For polio, which caused major devastation and disability across the world, research on a vaccine started in the 1940s. In 1950, an early version of the vaccine was created by Dr Salk. In 1954, the clinical trials began on around two million American schoolchildren and the vaccine was announced to be safe in 1955. However, that year in April, 2 lakh kids received a defective dose of the vaccine manufactured by Cutter Laboratories, causing paralysis within a month of the first mass vaccination programme, leading to 40,000 polio cases. One paper places the blame on the regulatory practices of the federal government and not on Salk; and eventually, an oral polio vaccine was formulated which is in use even now.
However, all of the above examples make it evident that figuring out vaccines is a tricky, time-consuming and risky business. The chicken pox vaccine took over three decades. And even now, research and development for vaccines for several viral diseases like HIV (over 30 years and counting) and Nipah virus are still ongoing.
Vaccine development happens in five, time-consuming stages. According to Wellcome, an independent UK based organisation that works on health advocacy, vaccine development, research and so on, the first stage of discovery research usually takes 2-5 years and can have up to 100 potential candidates. The preclinical stage sees narrowing down of the vaccine candidates and takes two years.
The clinical development happens in three phases: phase one (1-2 years) involving 20-80 participants to test the safety of the vaccine; phase two (2-3 years) involving several hundred individual participants to gauge if the vaccine activates an immune response; and phase three (2-4 years) to see if it protects against the disease. Phase three trials can take the longest because enough participants (thousands to tens of thousands) have to be exposed to the pathogen naturally.
The fourth step is to get the regulatory review and approval for the vaccine which can take 1-2 years before it goes to manufacturing and delivery. Generally, vaccine development can take over 10 years and $500 million.
All of this also depends on steady funding – research into the SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) vaccines for instance slowed down or was shelved when the epidemic was no longer perceived as a threat.
So, how are we progressing so quickly on the coronavirus vaccine front?
One of the possible reasons is that the SARS-CoV-2 vaccine, which causes COVID-19, is from the family of coronaviruses that scientists have studied before. This meant that they could quickly adapt the vaccine projects in the works for previous coronaviruses like the SARS virus and MERS virus. The spike protein which had been pointed out earlier as a component of the coronaviruses, was identified as a target for the vaccine. “SARS-2 is quite similar to SARS-1, especially in that spike protein. People could take a very educated guess that this is the protein that we need to be going after,” Rama Rao Amara, an immunologist and vaccine researcher at Emory University told Stat News.
Further, technology as well as research on genetics, immunology etc., have advanced by leaps, making it possible for scientists to skip the lengthy process of isolating and weakening the virus, and instead get the genetic code to use to develop some of the vaccine candidates. There is a chance that phase three clinical trials – which take longest – could also be completed in a shorter period of time given the wave of COVID-19 infections and a large number of people already being naturally exposed to the virus. Additionally, approvals are likely to come in quickly if the safety and efficacy are proven, thanks to the crisis situation at this point of time.
Despite these developments, the speed at which the vaccine development is progressing is also cause for caution. Manufacturing capacity, safety and regulations, usage of novel tech which has not been licensed yet, as well as conducting clinical trials during a pandemic are just some of the challenges that have been pointed out. Even Russia, which became the first country to grant regulatory approval to Sputnik V, a COVID-19 vaccine, is being questioned, and saw a top epidemiologist in the country resign over issues of ethics and safety in the vaccine development.
“It’s difficult to predict where and when outbreaks will occur and to prepare trial sites to coincide with vaccine readiness for testing. In addition, if multiple vaccines are ready for testing in the second half of 2020, it will be important not to crowd sites or burden countries and their ethics and regulatory authorities with multiple trials, as happened with Ebola therapeutics during the 2013–2016 outbreak,” Dr Nicole Lurie writes in this paper.
Further, it remains to be seen whether vaccine research and development will continue if the risk and threat of COVID-19 reduces going further into the pandemic, and if the political and financial interest in it dwindles as a result.